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</svg> Books</a></div><div class="jr-rhead f1 flexh"><div class="head"></div><div class="body"><div class="t">Colorectal Cancer Prevention (PDQ®): Health Professional Version</div><div class="j">PDQ Cancer Information Summaries [Internet]</div></div><div class="tail"></div></div><div id="jr-tb2"><a id="jr-bkhelp-sw" class="btn wsprkl hidden" title="Help with NLM PubReader">?</a><a id="jr-help-sw" class="btn wsprkl hidden" title="Settings and typography in NLM PubReader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512" preserveAspectRatio="none"><path d="M462,283.742v-55.485l-29.981-10.662c-11.431-4.065-20.628-12.794-25.274-24.001 c-0.002-0.004-0.004-0.009-0.006-0.013c-4.659-11.235-4.333-23.918,0.889-34.903l13.653-28.724l-39.234-39.234l-28.72,13.652 c-10.979,5.219-23.68,5.546-34.908,0.889c-0.005-0.002-0.01-0.003-0.014-0.005c-11.215-4.65-19.933-13.834-24-25.273L283.741,50 h-55.484l-10.662,29.981c-4.065,11.431-12.794,20.627-24.001,25.274c-0.005,0.002-0.009,0.004-0.014,0.005 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class="title" itemprop="name">Colorectal Cancer Prevention (PDQ®)</span></h1><div class="subtitle whole_rhythm">Health Professional Version</div><p class="contribs">PDQ Screening and Prevention Editorial Board.</p><p class="fm-aai"><a href="#_NBK65779_pubdet_">Publication Details</a></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p id="CDR0000062763__1172">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about colorectal cancer prevention. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.</p><p id="CDR0000062763__1173">This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p></div><div id="CDR0000062763__937"><h2 id="_CDR0000062763__937_">Who Is at Risk?</h2><p id="CDR0000062763__938">For most people, the major factor that increases a person’s risk for colorectal cancer (CRC) is advancing age. Risk increases dramatically after age 50 years; 90% of all CRCs are diagnosed after this age. Incidence and mortality rates are higher in African American individuals compared with other races; however, a meta-analysis found no evidence that African American individuals have higher rates of precancerous lesions.[<a class="bibr" href="#CDR0000062763_rl_937_1" rid="CDR0000062763_rl_937_1">1</a>,<a class="bibr" href="#CDR0000062763_rl_937_2" rid="CDR0000062763_rl_937_2">2</a>] The history of CRC in a first-degree relative, especially if before the age of 55 years, roughly doubles the risk. A personal history of CRC, high-risk adenomas, or ovarian cancer also increase the risk.[<a class="bibr" href="#CDR0000062763_rl_937_3" rid="CDR0000062763_rl_937_3">3</a>] Other risk factors are weaker than age and family history.
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People with an inflammatory bowel disease, such as ulcerative colitis or Crohn disease, have a much higher risk of CRC starting about 8 years after disease onset and are recommended to have frequent colonoscopic surveillance.[<a class="bibr" href="#CDR0000062763_rl_937_4" rid="CDR0000062763_rl_937_4">4</a>] A small percentage (<5%) of CRCs occur in people with a genetic predisposition, including familial adenomatous polyposis and hereditary nonpolyposis coli.</p><div id="CDR0000062763_rl_937"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062763_rl_937_1">Imperiale TF, Abhyankar PR, Stump TE, et al.: Prevalence of Advanced, Precancerous Colorectal Neoplasms in Black and White Populations: A Systematic Review and Meta-analysis. Gastroenterology 155 (6): 1776-1786.e1, 2018. [<a href="https://pubmed.ncbi.nlm.nih.gov/30142339" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30142339</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_937_2">Lansdorp-Vogelaar I, Kuntz KM, Knudsen AB, et al.: Contribution of screening and survival differences to racial disparities in colorectal cancer rates. Cancer Epidemiol Biomarkers Prev 21 (5): 728-36, 2012. [<a href="/pmc/articles/PMC3531983/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3531983</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22514249" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22514249</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_937_3">Imperiale TF, Juluri R, Sherer EA, et al.: A risk index for advanced neoplasia on the second surveillance colonoscopy in patients with previous adenomatous polyps. Gastrointest Endosc 80 (3): 471-8, 2014. [<a href="https://pubmed.ncbi.nlm.nih.gov/24890416" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24890416</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_937_4">Laukoetter MG, Mennigen R, Hannig CM, et al.: Intestinal cancer risk in Crohn's disease: a meta-analysis. J Gastrointest Surg 15 (4): 576-83, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/21152994" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21152994</span></a>]</div></li></ol></div></div><div id="CDR0000062763__1"><h2 id="_CDR0000062763__1_"> Overview</h2><p id="CDR0000062763__2">Note: The Overview section summarizes the published evidence on this topic. The rest of the summary describes the evidence in more detail.</p><p id="CDR0000062763__1278">
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Other PDQ summaries on <a href="/books/n/pdqcis/CDR0000062753/?report=reader">Colorectal Cancer Screening</a>; <a href="/books/n/pdqcis/CDR0000062687/?report=reader">Colon Cancer
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Treatment</a>; and <a href="/books/n/pdqcis/CDR0000062726/?report=reader">Rectal Cancer Treatment</a> are also available.</p><div id="CDR0000062763__150"><h3> Factors With Adequate Evidence of Increased Risk of Colorectal Cancer</h3><div id="CDR0000062763__231"><h4> Excessive alcohol use</h4><p id="CDR0000062763__939">Based on solid evidence from observational studies, excessive alcohol use is associated with an increased risk of colorectal cancer (CRC).[<a class="bibr" href="#CDR0000062763_rl_1_1" rid="CDR0000062763_rl_1_1">1</a>,<a class="bibr" href="#CDR0000062763_rl_1_2" rid="CDR0000062763_rl_1_2">2</a>]</p><p id="CDR0000062763__940"><b>Magnitude of Effect</b>: A pooled analysis of eight cohort studies estimated an adjusted relative risk (RR) of 1.41 (95% confidence interval [CI], 1.16–1.72) for consumption exceeding 45 g/day.[<a class="bibr" href="#CDR0000062763_rl_1_1" rid="CDR0000062763_rl_1_1">1</a>]</p><ul id="CDR0000062763__941" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Cohort studies.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Fair.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Fair.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Fair.</div></li></ul></div><div id="CDR0000062763__942"><h4>Cigarette smoking</h4><p id="CDR0000062763__943">Based on solid evidence, cigarette smoking is associated with increased incidence of and mortality from CRC.</p><p id="CDR0000062763__944"><b>Magnitude of Effect</b>: A pooled analysis of 106 observational studies estimated an adjusted RR (current smokers vs. never smokers) of 1.18 for developing CRC (95% CI, 1.11–1.25).[<a class="bibr" href="#CDR0000062763_rl_1_3" rid="CDR0000062763_rl_1_3">3</a>,<a class="bibr" href="#CDR0000062763_rl_1_4" rid="CDR0000062763_rl_1_4">4</a>]</p><ul id="CDR0000062763__945" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: 106 observational studies.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Fair.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062763__946"><h4>Obesity</h4><p id="CDR0000062763__947">Based on solid evidence, obesity is associated with increased incidence of and mortality from CRC.</p><p id="CDR0000062763__948"><b>Magnitude of Effect</b>: In one large cohort study, the adjusted RR of developing colon cancer for women with a body mass index greater than 29 was 1.45 (95% CI, 1.02–2.07).[<a class="bibr" href="#CDR0000062763_rl_1_5" rid="CDR0000062763_rl_1_5">5</a>,<a class="bibr" href="#CDR0000062763_rl_1_6" rid="CDR0000062763_rl_1_6">6</a>] A similar increase in CRC mortality was found in another large cohort study.[<a class="bibr" href="#CDR0000062763_rl_1_7" rid="CDR0000062763_rl_1_7">7</a>,<a class="bibr" href="#CDR0000062763_rl_1_8" rid="CDR0000062763_rl_1_8">8</a>]</p><ul id="CDR0000062763__949" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Large cohort studies.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Fair.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062763__1233"><h4>Family/personal history of colorectal cancer and other hereditary conditions</h4><p id="CDR0000062763__1234">Based on solid evidence, a family history of CRC in a first-degree relative or a personal history of CRC increases the risk of CRC.[<a class="bibr" href="#CDR0000062763_rl_1_9" rid="CDR0000062763_rl_1_9">9</a>-<a class="bibr" href="#CDR0000062763_rl_1_12" rid="CDR0000062763_rl_1_12">12</a>] Having a genetic predisposition, including familial adenomatous polyposis and hereditary nonpolyposis coli, also increases risk of CRC.[<a class="bibr" href="#CDR0000062763_rl_1_13" rid="CDR0000062763_rl_1_13">13</a>]</p><p id="CDR0000062763__1235"><b>Magnitude of Effect</b>: In persons with familial adenomatous polyposis, the risk of CRC by age 40 can be as high as 100%. Persons with Lynch syndrome can have a lifetime risk of CRC of about 80%.</p><ul id="CDR0000062763__1236" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Case-control and cohort studies.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul><p id="CDR0000062763__1237">For more information about family history and hereditary conditions, see <a href="/books/n/pdqcis/CDR0000062863/?report=reader">Genetics of Colorectal Cancer</a>.</p></div></div><div id="CDR0000062763__950"><h3>Factors With Adequate Evidence for a Decreased Risk of Colorectal Cancer </h3><div id="CDR0000062763__951"><h4>Physical activity</h4><p id="CDR0000062763__952">Based on solid evidence, regular physical activity is associated with a decreased incidence of CRC.</p><p id="CDR0000062763__953"><b>Magnitude of Effect</b>: A meta-analysis of 52 observational studies found a statistically significant 24% reduction in CRC incidence (RR, 0.76; 95% CI, 0.72–0.81).[<a class="bibr" href="#CDR0000062763_rl_1_14" rid="CDR0000062763_rl_1_14">14</a>]</p><ul id="CDR0000062763__954" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Cohort studies and meta-analysis.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Fair.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div></div><div id="CDR0000062763__955"><h3>Interventions With Adequate Evidence for a Decreased Risk of Colorectal Cancer</h3><div id="CDR0000062763__964"><h4>Aspirin: benefits</h4><p id="CDR0000062763__965">Based on solid evidence, daily aspirin (acetylsalicylic acid [ASA]) reduces CRC incidence and mortality after 10 to 20 years. This is based on three individual participant-level data meta-analyses of trials of aspirin used for the primary and secondary prevention of cardiovascular disease.[<a class="bibr" href="#CDR0000062763_rl_1_15" rid="CDR0000062763_rl_1_15">15</a>-<a class="bibr" href="#CDR0000062763_rl_1_17" rid="CDR0000062763_rl_1_17">17</a>]</p><p id="CDR0000062763__966"><b>Magnitude of Effect</b>: ASA use reduces the long-term risk of developing CRC by 40% about 10 to 19 years after initiation (hazard ratio [HR], 0.60; 95% CI, 0.47–0.76).[<a class="bibr" href="#CDR0000062763_rl_1_18" rid="CDR0000062763_rl_1_18">18</a>] Daily doses of 75 to 1,200 mg of ASA reduce the 20-year risk of CRC death by approximately 33% (HR, 0.67; 95% CI, 0.52–0.86).[<a class="bibr" href="#CDR0000062763_rl_1_16" rid="CDR0000062763_rl_1_16">16</a>,<a class="bibr" href="#CDR0000062763_rl_1_17" rid="CDR0000062763_rl_1_17">17</a>]</p><ul id="CDR0000062763__967" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Individual patient-level data meta-analyses of randomized controlled trials (RCTs) of ASA for primary and secondary cardiovascular prevention.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Fair, some data from registries and death certificates, some loss to follow-up; variations in ASA dose and timing; adherence to ASA unknown after end of trials (5–9 years); trials designed to answer a different primary hypothesis (cardiovascular disease prevention).</div></li><li class="half_rhythm"><div><b>Consistency</b>: Generally consistent.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Fair, most data (>75%) from men.</div></li></ul></div><div id="CDR0000062763__1264"><h4>Aspirin: harms</h4><p id="CDR0000062763__969">Based on solid evidence, harms of ASA use include excessive bleeding, including gastrointestinal bleeds and hemorrhagic stroke.</p><p id="CDR0000062763__970"><b>Magnitude of Effect</b>: Very low-dose ASA use (i.e., ≤100 mg every day or every other day) results in an estimated 14 (95% CI, 7–23) additional major gastrointestinal bleeding events and 3.2 (95% CI, -0.5 to 0.82) extra hemorrhagic strokes per 1,000 persons over 10 years. These risks increase with advancing age.[<a class="bibr" href="#CDR0000062763_rl_1_19" rid="CDR0000062763_rl_1_19">19</a>]</p><ul id="CDR0000062763__971" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Evidence obtained from RCTs, cohort studies, and meta-analyses comparing ASA with placebo or no treatment for the primary prevention of cardiovascular disease.[<a class="bibr" href="#CDR0000062763_rl_1_19" rid="CDR0000062763_rl_1_19">19</a>]</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Fair, data are from clinically and methodologically heterogeneous trials.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Fair, data on specific subgroups are limited.</div></li></ul></div><div id="CDR0000062763__1114"><h4>Hormone therapy (estrogen plus progestin): benefits</h4><p id="CDR0000062763__1115">Based on solid evidence, combined hormone therapy (conjugated equine estrogen and progestin) decreases the incidence of invasive CRC.[<a class="bibr" href="#CDR0000062763_rl_1_20" rid="CDR0000062763_rl_1_20">20</a>]</p><p id="CDR0000062763__1116">Based on fair evidence, combination conjugated equine estrogen and progestin has little or no benefit in reducing mortality from CRC. Data from the Women’s Health Initiative (WHI), a randomized, placebo-controlled trial evaluating estrogen plus progestin, with a mean intervention of 5.6 years and a follow-up of 11.6 years, showed that women taking combined hormone therapy had a statistically significant higher stage of cancer (regional and distant) at diagnosis but not a statistically significant number of deaths from CRC compared with women taking the placebo.[<a class="bibr" href="#CDR0000062763_rl_1_20" rid="CDR0000062763_rl_1_20">20</a>]</p><p id="CDR0000062763__1117"><b>Magnitude of Effect</b>: There were fewer CRCs in the combined hormone therapy group than in the placebo group (0.12% vs. 0.16%; HR, 0.72; 95% CI, 0.56–0.94). A meta-analysis of cohort studies observed a RR of 0.86 (95% CI, 0.76–0.97) for incidence of CRC associated with combined hormone therapy.</p><p id="CDR0000062763__1118">There were 37 CRC deaths in the combined hormone therapy arm compared with 27 deaths in the placebo arm (0.04% vs. 0.03%; HR, 1.29; 95% CI, 0.78–2.11).</p><ul id="CDR0000062763__1119" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: RCT and cohort studies.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good for effect on incidence; not applicable (N/A) for effect on mortality; results were based on one trial.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062763__1282"><h4>Hormone therapy (estrogen plus progestin): harms</h4><p id="CDR0000062763__1179">Based on solid evidence, harms of postmenopausal combined estrogen-plus-progestin hormone use include increased risk of breast cancer, coronary heart disease, and thromboembolic events.</p><p id="CDR0000062763__1180"><b>Magnitude of Effect</b>: The WHI showed a 26% increase in invasive breast cancer in the combined hormone group, a 29% increase in coronary heart disease events, a 41% increase in stroke rates, and a twofold higher rate of thromboembolic events.[<a class="bibr" href="#CDR0000062763_rl_1_21" rid="CDR0000062763_rl_1_21">21</a>]</p><ul id="CDR0000062763__979" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Evidence from RCTs.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Fair.</div></li></ul></div><div id="CDR0000062763__980"><h4>Polyp removal: benefits</h4><p id="CDR0000062763__981">Based on fair evidence, removal of adenomatous polyps reduces the risk of CRC. Much of this reduction likely comes from removal of large (i.e., >1.0 cm) polyps, while the benefit of removing smaller polyps—which are much more common—is unknown. Some but not all observational evidence indicates that this reduction may be greater for left-sided CRC than for right-sided CRC.[<a class="bibr" href="#CDR0000062763_rl_1_22" rid="CDR0000062763_rl_1_22">22</a>-<a class="bibr" href="#CDR0000062763_rl_1_24" rid="CDR0000062763_rl_1_24">24</a>]</p><p id="CDR0000062763__982"><b>Magnitude of Effect</b>: Unknown, probably greater for larger polyps (i.e., >1.0 cm) than for smaller ones.[<a class="bibr" href="#CDR0000062763_rl_1_25" rid="CDR0000062763_rl_1_25">25</a>]</p><ul id="CDR0000062763__983" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Evidence obtained from cohort studies and one RCT of sigmoidoscopy.[<a class="bibr" href="#CDR0000062763_rl_1_23" rid="CDR0000062763_rl_1_23">23</a>]</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Consistent.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062763__1265"><h4>Polyp removal: harms</h4><p id="CDR0000062763__985">Based on solid evidence, the major harms of polyp removal include perforation of the colon and bleeding.</p><p id="CDR0000062763__986"><b>Magnitude of Effect</b>: Seven to nine events per 1,000 procedures.[<a class="bibr" href="#CDR0000062763_rl_1_26" rid="CDR0000062763_rl_1_26">26</a>-<a class="bibr" href="#CDR0000062763_rl_1_28" rid="CDR0000062763_rl_1_28">28</a>]</p><ul id="CDR0000062763__987" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Evidence from retrospective cohort studies.[<a class="bibr" href="#CDR0000062763_rl_1_27" rid="CDR0000062763_rl_1_27">27</a>,<a class="bibr" href="#CDR0000062763_rl_1_28" rid="CDR0000062763_rl_1_28">28</a>]</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div></div><div id="CDR0000062763__1152"><h3>Factors With Inadequate Evidence of an Association With Colorectal Cancer</h3><div id="CDR0000062763__1153"><h4>Nonsteroidal anti-inflammatory drugs (NSAIDs): benefits</h4><p id="CDR0000062763__1155">There is inadequate evidence that the use of NSAIDs reduces the risk of CRC. In people without genetic predisposition but with a prior history of a colonic adenoma that had been removed, three RCTs found that celecoxib [<a class="bibr" href="#CDR0000062763_rl_1_29" rid="CDR0000062763_rl_1_29">29</a>,<a class="bibr" href="#CDR0000062763_rl_1_30" rid="CDR0000062763_rl_1_30">30</a>] and rofecoxib [<a class="bibr" href="#CDR0000062763_rl_1_31" rid="CDR0000062763_rl_1_31">31</a>] decreased the incidence of recurrent adenoma, although follow-up was too short to determine whether CRC incidence or mortality would have been affected.</p><p id="CDR0000062763__1156">Based on solid evidence, NSAIDs reduce the risk of adenomas, but the extent to which this translates into a reduction of CRC is uncertain.[<a class="bibr" href="#CDR0000062763_rl_1_32" rid="CDR0000062763_rl_1_32">32</a>]</p><ul id="CDR0000062763__1157" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: No adequate studies with CRC outcome.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: N/A.</div></li><li class="half_rhythm"><div><b>Consistency</b>: N/A.</div></li><li class="half_rhythm"><div><b>External Validity</b>: N/A.</div></li></ul></div><div id="CDR0000062763__1266"><h4>NSAIDs: harms</h4><p id="CDR0000062763__1159">Based on solid evidence, harms of NSAID use are relatively common and potentially serious, and include upper gastrointestinal bleeding, chronic kidney disease, and serious cardiovascular events such as myocardial infarction, heart failure, and hemorrhagic stroke.[<a class="bibr" href="#CDR0000062763_rl_1_33" rid="CDR0000062763_rl_1_33">33</a>] A recent report compared the cyclooxygenase-2 (COX-2) inhibitor celecoxib (200 mg/d) with the nonselective nonsteroidals naproxen (850 mg/d) and ibuprofen (2,000 mg/d) in individuals with severe arthritis (i.e., not using lower doses as for primary prevention). The results showed that serious cardiovascular events were not less common for those taking the nonselective nonsteroidals. However, this study did not assess the comparative safety of lower doses or the safety of the COX-2 inhibitor rofecoxib.[<a class="bibr" href="#CDR0000062763_rl_1_34" rid="CDR0000062763_rl_1_34">34</a>]</p><p id="CDR0000062763__1160"><b>Magnitude of Effect</b>: The estimated average excess risk of upper gastrointestinal complications in average-risk people attributable to NSAIDs is 4 to 5 per 1,000 people per year.[<a class="bibr" href="#CDR0000062763_rl_1_35" rid="CDR0000062763_rl_1_35">35</a>,<a class="bibr" href="#CDR0000062763_rl_1_36" rid="CDR0000062763_rl_1_36">36</a>] The excess risk varies with the underlying gastrointestinal risk; however, it likely exceeds ten extra cases per 1,000 people per year in more than 10% of users.[<a class="bibr" href="#CDR0000062763_rl_1_37" rid="CDR0000062763_rl_1_37">37</a>] Serious cardiovascular events are increased by 50% to 60%.[<a class="bibr" href="#CDR0000062763_rl_1_36" rid="CDR0000062763_rl_1_36">36</a>]</p><ul id="CDR0000062763__1161" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Evidence obtained from RCTs and high-quality systematic reviews and meta-analyses.[<a class="bibr" href="#CDR0000062763_rl_1_35" rid="CDR0000062763_rl_1_35">35</a>,<a class="bibr" href="#CDR0000062763_rl_1_36" rid="CDR0000062763_rl_1_36">36</a>]</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div><div id="CDR0000062763__1174"><h4>Calcium supplementation</h4><p id="CDR0000062763__1175">The evidence is inadequate to determine whether calcium supplementation reduces the risk of CRC.</p></div><div id="CDR0000062763__1221"><h4>Dietary factors</h4><p id="CDR0000062763__1222">There is no reliable evidence that a diet started in adulthood that is low in fat and meat and high in fiber, fruits, and vegetables reduces the risk of CRC by a clinically important degree.</p></div></div><div id="CDR0000062763__1134"><h3>Factors and Interventions With Adequate Evidence of no Association With Colorectal Cancer</h3><div id="CDR0000062763__1135"><h4>Estrogen-only therapy: benefits</h4><p id="CDR0000062763__1140">Based on fair evidence, conjugated equine estrogens do not affect the incidence of or mortality from invasive CRC.[<a class="bibr" href="#CDR0000062763_rl_1_38" rid="CDR0000062763_rl_1_38">38</a>]</p><p id="CDR0000062763__1137"><b>Magnitude of Effect</b>: N/A.</p><ul id="CDR0000062763__1138" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Evidence from RCTs.</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Fair.</div></li></ul></div><div id="CDR0000062763__1145"><h4>Statins: benefits</h4><p id="CDR0000062763__1147">Based on solid evidence, statins do not reduce the incidence of or mortality from CRC.</p><ul id="CDR0000062763__1148" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Meta-analyses of RCTs.[<a class="bibr" href="#CDR0000062763_rl_1_39" rid="CDR0000062763_rl_1_39">39</a>-<a class="bibr" href="#CDR0000062763_rl_1_41" rid="CDR0000062763_rl_1_41">41</a>] </div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: N/A.</div></li></ul></div><div id="CDR0000062763__1267"><h4>Statins: harms</h4><p id="CDR0000062763__1150">Based on solid evidence, the harms of statins are small.</p><ul id="CDR0000062763__1151" class="simple-list"><li class="half_rhythm"><div><b>Study Design</b>: Observational studies,[<a class="bibr" href="#CDR0000062763_rl_1_42" rid="CDR0000062763_rl_1_42">42</a>] multiple RCTs, and a review.[<a class="bibr" href="#CDR0000062763_rl_1_43" rid="CDR0000062763_rl_1_43">43</a>]</div></li><li class="half_rhythm"><div><b>Internal Validity</b>: Good.</div></li><li class="half_rhythm"><div><b>Consistency</b>: Good.</div></li><li class="half_rhythm"><div><b>External Validity</b>: Good.</div></li></ul></div></div><div id="CDR0000062763_rl_1"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062763_rl_1_1">Cho E, Smith-Warner SA, Ritz J, et al.: Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies. 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[<a href="/pmc/articles/PMC1473048/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1473048</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16740558" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16740558</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1_37">Hernández-Díaz S, García Rodríguez LA: Cardioprotective aspirin users and their excess risk of upper gastrointestinal complications. BMC Med 4: 22, 2006. [<a href="/pmc/articles/PMC1590044/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1590044</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16987411" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16987411</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1_38">Ritenbaugh C, Stanford JL, Wu L, et al.: Conjugated equine estrogens and colorectal cancer incidence and survival: the Women's Health Initiative randomized clinical trial. Cancer Epidemiol Biomarkers Prev 17 (10): 2609-18, 2008. [<a href="/pmc/articles/PMC2937217/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2937217</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18829444" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18829444</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1_39">Baigent C, Keech A, Kearney PM, et al.: Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366 (9493): 1267-78, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/16214597" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16214597</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1_40">Dale KM, Coleman CI, Henyan NN, et al.: Statins and cancer risk: a meta-analysis. JAMA 295 (1): 74-80, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16391219" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16391219</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1_41">Browning DR, Martin RM: Statins and risk of cancer: a systematic review and metaanalysis. Int J Cancer 120 (4): 833-43, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17131313" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17131313</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1_42">Hippisley-Cox J, Coupland C: Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ 340: c2197, 2010. [<a href="/pmc/articles/PMC2874131/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2874131</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20488911" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20488911</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1_43">Joy TR, Hegele RA: Narrative review: statin-related myopathy. Ann Intern Med 150 (12): 858-68, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19528564" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19528564</span></a>]</div></li></ol></div></div><div id="CDR0000062763__1008"><h2 id="_CDR0000062763__1008_">Incidence and Mortality</h2><p id="CDR0000062763__1009">Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide [<a class="bibr" href="#CDR0000062763_rl_1008_1" rid="CDR0000062763_rl_1008_1">1</a>] and
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the third leading cause of cancer deaths in men and women combined in the
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United States.[<a class="bibr" href="#CDR0000062763_rl_1008_2" rid="CDR0000062763_rl_1008_2">2</a>] It is estimated that there will be 152,810 new cases diagnosed in the United States in 2024 and
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53,010 deaths due to this disease.[<a class="bibr" href="#CDR0000062763_rl_1008_2" rid="CDR0000062763_rl_1008_2">2</a>] Between 2011 and 2019, incidence rates for CRC in the United States declined by about 1% per year overall. However, this declining incidence is confined to individuals aged 65 years and older. Since the mid-1990s, incidence rates increased by 1% to 2% per year in individuals younger than 55 years and stabilized in individuals aged 55 to 64 years.[<a class="bibr" href="#CDR0000062763_rl_1008_2" rid="CDR0000062763_rl_1008_2">2</a>] For the past 50 years, the mortality rate for CRC has been declining in both men and women. Over the last decade, the mortality rate declined by 1.8% per year.[<a class="bibr" href="#CDR0000062763_rl_1008_2" rid="CDR0000062763_rl_1008_2">2</a>] Incidence and mortality rates are higher in Black individuals than in those of other races; however, a meta-analysis found no evidence that Black individuals have higher rates of precancerous lesions.[<a class="bibr" href="#CDR0000062763_rl_1008_3" rid="CDR0000062763_rl_1008_3">3</a>-<a class="bibr" href="#CDR0000062763_rl_1008_5" rid="CDR0000062763_rl_1008_5">5</a>]</p><p id="CDR0000062763__1162">The overall 5-year survival rate is 65% for CRC. About 4% of
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Americans are expected to develop CRC within their lifetimes.[<a class="bibr" href="#CDR0000062763_rl_1008_2" rid="CDR0000062763_rl_1008_2">2</a>,<a class="bibr" href="#CDR0000062763_rl_1008_6" rid="CDR0000062763_rl_1008_6">6</a>] The
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risk of CRC begins to increase after the age of 40 years and rises
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sharply at ages 50 to 55 years; the risk doubles with each succeeding decade
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and continues to rise exponentially. Despite advances in surgical techniques
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and adjuvant therapy, there has been only a modest improvement in survival for
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patients who present with advanced neoplasms.[<a class="bibr" href="#CDR0000062763_rl_1008_7" rid="CDR0000062763_rl_1008_7">7</a>,<a class="bibr" href="#CDR0000062763_rl_1008_8" rid="CDR0000062763_rl_1008_8">8</a>] Hence, effective primary
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and secondary preventive approaches must be developed to reduce the morbidity
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and mortality from CRC.</p><div id="CDR0000062763_rl_1008"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062763_rl_1008_1">Shike M, Winawer SJ, Greenwald PH, et al.: Primary prevention of colorectal cancer. The WHO Collaborating Centre for the Prevention of Colorectal Cancer. Bull World Health Organ 68 (3): 377-85, 1990. [<a href="/pmc/articles/PMC2393072/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2393072</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/2203551" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2203551</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1008_2">American Cancer Society: Cancer Facts and Figures 2024. American Cancer Society, 2024. <a href="https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed December 30, 2024.</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1008_3">Imperiale TF, Abhyankar PR, Stump TE, et al.: Prevalence of Advanced, Precancerous Colorectal Neoplasms in Black and White Populations: A Systematic Review and Meta-analysis. Gastroenterology 155 (6): 1776-1786.e1, 2018. [<a href="https://pubmed.ncbi.nlm.nih.gov/30142339" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30142339</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1008_4">Laiyemo AO, Doubeni C, Pinsky PF, et al.: Race and colorectal cancer disparities: health-care utilization vs different cancer susceptibilities. J Natl Cancer Inst 102 (8): 538-46, 2010. [<a href="/pmc/articles/PMC2857802/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2857802</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20357245" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20357245</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1008_5">Lansdorp-Vogelaar I, Kuntz KM, Knudsen AB, et al.: Contribution of screening and survival differences to racial disparities in colorectal cancer rates. Cancer Epidemiol Biomarkers Prev 21 (5): 728-36, 2012. [<a href="/pmc/articles/PMC3531983/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3531983</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22514249" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22514249</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1008_6">Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. <a href="https://seer.cancer.gov/statistics-network/explorer/" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed December 30, 2024.</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1008_7">Moertel CG, Fleming TR, Macdonald JS, et al.: Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 322 (6): 352-8, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2300087" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2300087</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1008_8">Krook JE, Moertel CG, Gunderson LL, et al.: Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 324 (11): 709-15, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1997835" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1997835</span></a>]</div></li></ol></div></div><div id="CDR0000062763__1010"><h2 id="_CDR0000062763__1010_">Definition of Prevention</h2><p id="CDR0000062763__1011">Primary prevention involves the use of medications or other interventions before the clinical appearance of colorectal cancer (CRC) with the intent of preventing clinical CRC and CRC mortality.</p></div><div id="CDR0000062763__1012"><h2 id="_CDR0000062763__1012_">Etiology and Pathogenesis of Colorectal Cancer</h2><p id="CDR0000062763__1013">Genetics,[<a class="bibr" href="#CDR0000062763_rl_1012_1" rid="CDR0000062763_rl_1012_1">1</a>,<a class="bibr" href="#CDR0000062763_rl_1012_2" rid="CDR0000062763_rl_1012_2">2</a>] experimental,[<a class="bibr" href="#CDR0000062763_rl_1012_3" rid="CDR0000062763_rl_1012_3">3</a>,<a class="bibr" href="#CDR0000062763_rl_1012_4" rid="CDR0000062763_rl_1012_4">4</a>] and epidemiologic [<a class="bibr" href="#CDR0000062763_rl_1012_5" rid="CDR0000062763_rl_1012_5">5</a>-<a class="bibr" href="#CDR0000062763_rl_1012_7" rid="CDR0000062763_rl_1012_7">7</a>] studies suggest
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that colorectal cancer (CRC) results from complex interactions between inherited
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susceptibility and environmental factors. The exact nature and contribution of these factors to CRC incidence and mortality is the subject of ongoing research.</p><div id="CDR0000062763_rl_1012"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062763_rl_1012_1">Willett W: The search for the causes of breast and colon cancer. Nature 338 (6214): 389-94, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2648156" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2648156</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1012_2">Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 61 (5): 759-67, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2188735" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2188735</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1012_3">Reddy B, Engle A, Katsifis S, et al.: Biochemical epidemiology of colon cancer: effect of types of dietary fiber on fecal mutagens, acid, and neutral sterols in healthy subjects. Cancer Res 49 (16): 4629-35, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2545348" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2545348</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1012_4">Reddy BS, Tanaka T, Simi B: Effect of different levels of dietary trans fat or corn oil on azoxymethane-induced colon carcinogenesis in F344 rats. J Natl Cancer Inst 75 (4): 791-8, 1985. [<a href="https://pubmed.ncbi.nlm.nih.gov/3862909" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3862909</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1012_5">Potter JD: Reconciling the epidemiology, physiology, and molecular biology of colon cancer. JAMA 268 (12): 1573-7, 1992 Sep 23-30. [<a href="https://pubmed.ncbi.nlm.nih.gov/1518112" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1518112</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1012_6">Wynder EL, Reddy BS: Dietary fat and fiber and colon cancer. Semin Oncol 10 (3): 264-72, 1983. [<a href="https://pubmed.ncbi.nlm.nih.gov/6320447" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6320447</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1012_7">Chen CD, Yen MF, Wang WM, et al.: A case-cohort study for the disease natural history of adenoma-carcinoma and de novo carcinoma and surveillance of colon and rectum after polypectomy: implication for efficacy of colonoscopy. Br J Cancer 88 (12): 1866-73, 2003. [<a href="/pmc/articles/PMC2741116/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2741116</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/12799628" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12799628</span></a>]</div></li></ol></div></div><div id="CDR0000062763__1014"><h2 id="_CDR0000062763__1014_">Factors With Adequate Evidence of Increased Risk of Colorectal Cancer</h2><div id="CDR0000062763__1015"><h3>Excessive Alcohol Use</h3><p id="CDR0000062763__1016">There is evidence of an association of colorectal cancer (CRC) with alcoholic beverage consumption. In a meta-analysis of eight cohort studies, the relative risk (RR) for consumption of 45 g/day (i.e., about three standard drinks per day) compared with nondrinkers was 1.41 (95% confidence interval [CI], 1.16–1.72).[<a class="bibr" href="#CDR0000062763_rl_1014_1" rid="CDR0000062763_rl_1014_1">1</a>] Case-control studies suggest a modest-to-strong positive relationship between alcohol consumption and large bowel cancers.[<a class="bibr" href="#CDR0000062763_rl_1014_2" rid="CDR0000062763_rl_1014_2">2</a>,<a class="bibr" href="#CDR0000062763_rl_1014_3" rid="CDR0000062763_rl_1014_3">3</a>] A meta-analysis found that the association did not vary by sex or location within the large bowel.[<a class="bibr" href="#CDR0000062763_rl_1014_4" rid="CDR0000062763_rl_1014_4">4</a>]</p><p id="CDR0000062763__1017">Five studies have reported a positive association between alcohol intake and colorectal adenomas.[<a class="bibr" href="#CDR0000062763_rl_1014_5" rid="CDR0000062763_rl_1014_5">5</a>] A case-control study of diet, genetic factors, and the adenoma-carcinoma sequence was conducted in Burgundy.[<a class="bibr" href="#CDR0000062763_rl_1014_6" rid="CDR0000062763_rl_1014_6">6</a>] It separated adenomas smaller than 10.0 mm in diameter from larger adenomas. A positive association between current alcohol intake and adenomas was found to be limited to the larger adenomas, suggesting that alcohol intake could act at the promotional phase of the adenoma-carcinoma sequence.[<a class="bibr" href="#CDR0000062763_rl_1014_6" rid="CDR0000062763_rl_1014_6">6</a>]</p><p id="CDR0000062763__1018">A large cohort study found a dose-response relationship between alcohol intake and death from CRC, with a RR of 1.2 (95% CI, 1.0–1.5) for four or more drinks per day compared with nondrinkers.[<a class="bibr" href="#CDR0000062763_rl_1014_7" rid="CDR0000062763_rl_1014_7">7</a>]</p></div><div id="CDR0000062763__1019"><h3>Cigarette Smoking</h3><p id="CDR0000062763__1020"> Most case-control studies of cigarette exposure and adenomas have found an
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elevated risk for smokers.[<a class="bibr" href="#CDR0000062763_rl_1014_8" rid="CDR0000062763_rl_1014_8">8</a>] In addition, a significantly increased risk of
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adenoma recurrence following polypectomy has been associated with smoking in
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both men and women.[<a class="bibr" href="#CDR0000062763_rl_1014_8" rid="CDR0000062763_rl_1014_8">8</a>] In the Nurses’ Health Study, the minimum induction
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period for cancer appears to be at least 35 years.[<a class="bibr" href="#CDR0000062763_rl_1014_9" rid="CDR0000062763_rl_1014_9">9</a>] Similarly, in the
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Health Professionals Follow-up Study, a history of smoking was associated with
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both small and large adenomas and with a long induction period of at least 35
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years for CRC.[<a class="bibr" href="#CDR0000062763_rl_1014_10" rid="CDR0000062763_rl_1014_10">10</a>] In the Cancer Prevention Study II (CPS II), a
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large nationwide cohort study, multivariate-adjusted CRC
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mortality rates were highest among current smokers, intermediate among former
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smokers, and lowest in nonsmokers, with increased risk observed after 20 or
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more years of smoking in men and women combined.[<a class="bibr" href="#CDR0000062763_rl_1014_11" rid="CDR0000062763_rl_1014_11">11</a>] On the basis of CPS II data, it
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was estimated that 12% of CRC deaths in the U.S. population in
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1997 were attributable to smoking. A large population-based cohort study of
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Swedish twins found that heavy smoking of 35 or more years' duration was
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associated with a nearly threefold increased risk of developing colon cancer,
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although subsite analysis found a statistically significant effect only for
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rectal cancer, but not colon cancer.[<a class="bibr" href="#CDR0000062763_rl_1014_12" rid="CDR0000062763_rl_1014_12">12</a>] Another large population-based case-control
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study supports the view that current tobacco use and tobacco use within the
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last 10 years is associated with colon cancer. A 50% increase in risk was
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associated with smoking more than a pack a day relative to never smoking.[<a class="bibr" href="#CDR0000062763_rl_1014_13" rid="CDR0000062763_rl_1014_13">13</a>]
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However, a 28-year follow-up of 57,000 Finns showed no association between the
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development of CRC and baseline smoking status, although there
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was a 57% to 71% increased risk in persistent smokers.[<a class="bibr" href="#CDR0000062763_rl_1014_14" rid="CDR0000062763_rl_1014_14">14</a>] No relationship was
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found between cigarette smoking, even smoking of long duration, and recurrence
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of adenomas in a population followed for 4 years after initial colonoscopy.[<a class="bibr" href="#CDR0000062763_rl_1014_15" rid="CDR0000062763_rl_1014_15">15</a>]</p><p id="CDR0000062763__1021">A meta-analysis of 106 observational studies found a RR (ever smokers vs. nonsmokers) for CRC incidence of 1.18 (95% CI, 1.11–1.25), with an absolute risk increase of 10.8 cases per 100,000 person-years (95% CI, 7.9–13.6). There was a statistically significant dose-response effect. In 17 studies with data on CRC mortality, cigarette smoking was associated with CRC death, with a RR (ever smokers vs. never smokers) of 1.25 (95% CI, 1.14–1.37), and an absolute increase in the death rate of 6.0 deaths per 100,000 person-years. For both incidence and mortality, the association was stronger for rectal cancer than for colon cancer.[<a class="bibr" href="#CDR0000062763_rl_1014_16" rid="CDR0000062763_rl_1014_16">16</a>]</p></div><div id="CDR0000062763__1022"><h3>Obesity</h3><p id="CDR0000062763__1023">At least three large cohort studies have found an association between obesity and CRC incidence or mortality.[<a class="bibr" href="#CDR0000062763_rl_1014_17" rid="CDR0000062763_rl_1014_17">17</a>-<a class="bibr" href="#CDR0000062763_rl_1014_19" rid="CDR0000062763_rl_1014_19">19</a>] The Nurses’ Health Study found that women with a body mass index (BMI) of more than 29, compared with women with a BMI of less than 21, had an adjusted RR for CRC incidence of 1.45 (95% CI, 1.02–2.07).[<a class="bibr" href="#CDR0000062763_rl_1014_17" rid="CDR0000062763_rl_1014_17">17</a>] In the CPS II,[<a class="bibr" href="#CDR0000062763_rl_1014_19" rid="CDR0000062763_rl_1014_19">19</a>] men and women with a BMI of 30 to 34.9 had an adjusted RR for CRC mortality (compared with people with a BMI of 18.5–24.9) of 1.47 (95% CI, 1.30–1.66), with a statistically significant dose-response effect.[<a class="bibr" href="#CDR0000062763_rl_1014_19" rid="CDR0000062763_rl_1014_19">19</a>] The effects were similar in men and women. </p></div><div id="CDR0000062763__1242"><h3>Family/Personal History of Colorectal Cancer and Other Hereditary Conditions</h3><p id="CDR0000062763__1243">Some of the earliest studies of family history of CRC were those of Utah families that reported a higher number of deaths from CRC (3.9%) among the first-degree relatives of patients who had died from CRC than among sex-matched and age-matched controls (1.2%). This difference has since been replicated in numerous studies that have consistently found that first-degree relatives of affected cases are themselves at a twofold to threefold increased risk of CRC. Despite the various study designs (case-control, cohort), sampling frames, sample sizes, methods of data verification, analytic methods, and countries where the studies originated, the magnitude of risk is consistent.[<a class="bibr" href="#CDR0000062763_rl_1014_20" rid="CDR0000062763_rl_1014_20">20</a>-<a class="bibr" href="#CDR0000062763_rl_1014_25" rid="CDR0000062763_rl_1014_25">25</a>]</p><p id="CDR0000062763__1244">A systematic review and meta-analysis of familial CRC risk was reported.[<a class="bibr" href="#CDR0000062763_rl_1014_26" rid="CDR0000062763_rl_1014_26">26</a>] Of 24 studies included in the analysis, all but one reported an increased risk of CRC if there was an affected first-degree relative. The RR for CRC in the pooled study was 2.25 (95% CI, 2.00–2.53) if there was an affected first-degree family member. In 8 of 11 studies, if the index cancer arose in the colon, the risk was slightly higher than if it arose in the rectum. The pooled analysis revealed an RR in relatives of colon and rectal cancer patients of 2.42 (95% CI, 2.20–2.65) and 1.89 (95% CI, 1.62–2.21), respectively. The analysis did not reveal a difference in RR for colon cancer based on location of the tumor (right side vs. left side).[<a class="bibr" href="#CDR0000062763_rl_1014_26" rid="CDR0000062763_rl_1014_26">26</a>]</p><p id="CDR0000062763__1245">Hereditary CRC has two well-described forms: Familial adenomatous polyposis (including an attenuated form of polyposis), due to germline mutations in the <i>APC</i> gene,[<a class="bibr" href="#CDR0000062763_rl_1014_27" rid="CDR0000062763_rl_1014_27">27</a>-<a class="bibr" href="#CDR0000062763_rl_1014_34" rid="CDR0000062763_rl_1014_34">34</a>] and Lynch syndrome, which is caused by germline mutations in DNA mismatch repair genes.[<a class="bibr" href="#CDR0000062763_rl_1014_35" rid="CDR0000062763_rl_1014_35">35</a>-<a class="bibr" href="#CDR0000062763_rl_1014_38" rid="CDR0000062763_rl_1014_38">38</a>] Many other families exhibit aggregation of CRC and/or adenomas, but with no apparent association with an identifiable hereditary syndrome, and are known collectively as familial CRC.[<a class="bibr" href="#CDR0000062763_rl_1014_38" rid="CDR0000062763_rl_1014_38">38</a>]</p><p id="CDR0000062763__1248">For more information about genetic risk factors for CRC, see <a href="/books/n/pdqcis/CDR0000062863/?report=reader">Genetics of Colorectal Cancer</a>.</p></div><div id="CDR0000062763_rl_1014"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062763_rl_1014_1">Cho E, Smith-Warner SA, Ritz J, et al.: Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies. 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Numerous observational studies have examined the relationship between physical activity and colon cancer risk.[<a class="bibr" href="#CDR0000062763_rl_1024_4" rid="CDR0000062763_rl_1024_4">4</a>] Most of these studies have shown an inverse relationship between level of physical activity and colon cancer incidence. The average relative risk (RR) reduction is reportedly 40% to 50%. Large U.S. cohort studies have found statistically significant adjusted RRs of 0.54 (95% confidence interval [CI], 0.33–0.90) [<a class="bibr" href="#CDR0000062763_rl_1024_5" rid="CDR0000062763_rl_1024_5">5</a>] and 0.53 (95% CI, 0.32–0.88) [<a class="bibr" href="#CDR0000062763_rl_1024_6" rid="CDR0000062763_rl_1024_6">6</a>] when comparing people with high versus low average energy expenditure. A meta-analysis of 52 observational studies found an overall adjusted RR of 0.76 (95% CI, 0.72–0.81), with similar results for men and women.[<a class="bibr" href="#CDR0000062763_rl_1024_7" rid="CDR0000062763_rl_1024_7">7</a>]</p></div><div id="CDR0000062763_rl_1024"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062763_rl_1024_1">White E, Jacobs EJ, Daling JR: Physical activity in relation to colon cancer in middle-aged men and women. Am J Epidemiol 144 (1): 42-50, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8659484" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8659484</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1024_2">Slattery ML, Schumacher MC, Smith KR, et al.: Physical activity, diet, and risk of colon cancer in Utah. Am J Epidemiol 128 (5): 989-99, 1988. 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[<a href="https://pubmed.ncbi.nlm.nih.gov/11319168" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11319168</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1024_5">Martínez ME, Giovannucci E, Spiegelman D, et al.: Leisure-time physical activity, body size, and colon cancer in women. Nurses' Health Study Research Group. J Natl Cancer Inst 89 (13): 948-55, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9214674" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9214674</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1024_6">Giovannucci E, Ascherio A, Rimm EB, et al.: Physical activity, obesity, and risk for colon cancer and adenoma in men. Ann Intern Med 122 (5): 327-34, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7847643" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7847643</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1024_7">Wolin KY, Yan Y, Colditz GA, et al.: Physical activity and colon cancer prevention: a meta-analysis. Br J Cancer 100 (4): 611-6, 2009. [<a href="/pmc/articles/PMC2653744/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2653744</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19209175" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19209175</span></a>]</div></li></ol></div></div><div id="CDR0000062763__1181"><h2 id="_CDR0000062763__1181_">Interventions With Adequate Evidence for a Decreased Risk of Colorectal Cancer </h2><div id="CDR0000062763__1182"><h3>Aspirin</h3><p id="CDR0000062763__1183">Evidence from individual participant-level data meta-analyses of randomized controlled trials (RCTs) and observational studies [<a class="bibr" href="#CDR0000062763_rl_1181_1" rid="CDR0000062763_rl_1181_1">1</a>,<a class="bibr" href="#CDR0000062763_rl_1181_2" rid="CDR0000062763_rl_1181_2">2</a>] investigating the use of aspirin for the prevention of cardiovascular disease indicates that acetylsalicylic acid (ASA) use reduces the incidence of colorectal cancer (CRC), but not until at least 10 years after initiation of therapy (pooled relative risk [RR] of CRC incidence within 10 years of initiation, 0.99 [95% confidence interval (CI), 0.85–1.15] vs. RR, 0.60 [95% CI, 0.47–0.76] at 10–19 years after initiation).[<a class="bibr" href="#CDR0000062763_rl_1181_3" rid="CDR0000062763_rl_1181_3">3</a>] In the Women's Health Study, a randomized 2 × 2 factorial trial of 100 mg of ASA every other day for an average of 10 years, CRC incidence was reduced by about 20% after 17.5 years (hazard ratio [HR], 0.80; 95% CI, 0.67–0.97).[<a class="bibr" href="#CDR0000062763_rl_1181_4" rid="CDR0000062763_rl_1181_4">4</a>] In a report from the Nurses’ Health Study involving 82,911 women followed for 20 years, the multivariate RR for colon cancer was 0.77 (95% CI, 0.67–0.88) among women who regularly used ASA (≥2 standard 325-mg tablets per week) compared with nonregular use. Significant RR was not observed, however, until more than 10 years of use.[<a class="bibr" href="#CDR0000062763_rl_1181_5" rid="CDR0000062763_rl_1181_5">5</a>]</p><p id="CDR0000062763__1283">The Cancer Prevention Programme (CAPP2), previously known as the Concerted Action Polyposis Prevention project, investigated chemoprevention of CRC in patients with known Lynch syndrome across 43 international centers. For more information, see the <a href="/books/n/pdqcis/CDR0000062863/?report=reader#CDR0000062863__2986">Lynch Syndrome</a> section in Genetics of Colorectal Cancer. Patients were randomly assigned to receive aspirin (600 mg/day), aspirin-placebo, resistant starch (30 g/day), or starch-placebo for up to 4 years. A planned 10-year analysis of CAPP2 data found reduced CRC incidence in patients with Lynch syndrome who took aspirin for at least 2 years when compared with those who took placebo. An intention-to-treat analysis, using Cox proportional hazards regression, showed that aspirin protected against the primary end point of CRC (HR, 0.65; 95% CI, 0.43–0.97; <i>P</i> = .035).[<a class="bibr" href="#CDR0000062763_rl_1181_6" rid="CDR0000062763_rl_1181_6">6</a>]</p><p id="CDR0000062763__1186">In a randomized study of 635 patients with prior CRC (T1–T2 N0 M0) who had undergone curative resection, ASA intake at 325 mg/day was associated with a decrease in the adjusted RR of any recurrent adenoma as compared with the placebo group (0.65; 95% CI, 0.46–0.91) after a median duration of treatment of 31 months. The likelihood of detection of a new colonic lesion was lower in the ASA group than in the placebo group (HR for the detection of a new polyp, 0.54; 95% CI, 0.43–0.94, <i>P</i> = .022).[<a class="bibr" href="#CDR0000062763_rl_1181_7" rid="CDR0000062763_rl_1181_7">7</a>] In a study of 1,121 patients with a recent history of colorectal adenomas, after a mean duration of treatment of 33 months, the unadjusted RRs of any adenoma (as compared with the placebo group) were 0.81 in the 81 mg/day ASA group (95% CI, 0.69–0.96) and 0.96 in the 325 mg/day ASA group (95% CI, 0.81–1.13). For advanced neoplasms (adenomas ≥10.0 mm in diameter or with tubulovillous or villous features, severe dysplasia, or invasive cancer), the RRs were 0.59 (95% CI, 0.38–0.92) in the 81 mg/day ASA group, and 0.83 (95% CI, 0.55–1.23) in the 325 mg/day ASA group, respectively.[<a class="bibr" href="#CDR0000062763_rl_1181_8" rid="CDR0000062763_rl_1181_8">8</a>]</p><p id="CDR0000062763__1188">ASA has also been evaluated for its potential effects on CRC mortality. A 2010 individual patient level data meta-analysis analyzed long-term (median follow-up, 18.3 years) data from four RCTs of primary and secondary cardiovascular disease prevention; it found that allocation to use of 75 to 1,200 mg of daily ASA for at least one year reduced the cumulative risk of colon cancer death compared with controls (HR, 0.67; 95% CI, 0.52–0.86). Aspirin reduced CRC mortality beginning 10 to 20 years after randomization, but not before.[<a class="bibr" href="#CDR0000062763_rl_1181_2" rid="CDR0000062763_rl_1181_2">2</a>] A 2011 individual participant level data meta-analysis examined data from six RCTs of primary or secondary cardiovascular disease prevention. In trials with allocation to ASA after at least 5 years of in-trial follow-up, the HR for CRC mortality was 0.41 (95% CI, 0.71–1.00). There was no statistically significant effect during the first five years after randomization.[<a class="bibr" href="#CDR0000062763_rl_1181_9" rid="CDR0000062763_rl_1181_9">9</a>]</p><p id="CDR0000062763__1250">Six RCTs, including five from the United Kingdom, were included in a meta-analysis in which patients were randomly assigned to receive either aspirin or placebo, and the mean scheduled duration of trial treatment was 4 years or more. Individual patient data for all in-trial cancer deaths were obtained. In the three United Kingdom trials, cancer deaths after completion of the trials were obtained via death certification and cancer registration, taking the follow-up to 20 years after randomization. Based on meta-analysis of odds ratios (ORs) from each trial rather than on more sensitive actuarial analysis of the individual patient data, allocation to aspirin in the RCTs reduced the 20-year risk of death due to CRC. ORs for maximum aspirin use were 0.55 for CRC risk (95% CI, 0.41–0.76) and for any aspirin use were 0.58 for CRC risk (95% CI, 0.44–0.78).[<a class="bibr" href="#CDR0000062763_rl_1181_10" rid="CDR0000062763_rl_1181_10">10</a>]</p><p id="CDR0000062763__1190">The Women's Health Study, the largest randomized trial of aspirin to date (N = 39,876), found no reduction in CRC mortality rates with the use of every other day low-dose aspirin during the first 10 years of follow-up. The study did not report on longer-term risk for CRC mortality.[<a class="bibr" href="#CDR0000062763_rl_1181_4" rid="CDR0000062763_rl_1181_4">4</a>]</p><p id="CDR0000062763__1251">Aspirin has several important potential harms associated with its use that should be a part of any consideration of its use as a disease prevention strategy. Regular low-dose aspirin use increases the risks for major gastrointestinal bleeding and intracranial bleeding events, including hemorrhagic strokes. A systematic review of studies of aspirin use for primary cardiovascular disease prevention found that use of 100 mg or more of aspirin daily or every other day increased a person’s risk for a major gastrointestinal bleed by 58% (OR, 1.58; 95% CI, 1.29–1.95) or an intracranial hemorrhage by 30% (OR, 1.30; 95% CI, 1.00–1.68). These risks may be greater among older individuals, men, and those individuals with comorbid risk factors that promote a risk of bleeding.[<a class="bibr" href="#CDR0000062763_rl_1181_11" rid="CDR0000062763_rl_1181_11">11</a>]</p></div><div id="CDR0000062763__1191"><h3>Hormone Therapy (Estrogen Plus Progestin)</h3><p id="CDR0000062763__1192">Several observational studies have suggested a decreased risk of colon cancer
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among users of postmenopausal female hormone supplements.[<a class="bibr" href="#CDR0000062763_rl_1181_12" rid="CDR0000062763_rl_1181_12">12</a>-<a class="bibr" href="#CDR0000062763_rl_1181_15" rid="CDR0000062763_rl_1181_15">15</a>] For rectal
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cancer, most studies have observed no association or a slightly elevated risk.[<a class="bibr" href="#CDR0000062763_rl_1181_16" rid="CDR0000062763_rl_1181_16">16</a>-<a class="bibr" href="#CDR0000062763_rl_1181_18" rid="CDR0000062763_rl_1181_18">18</a>]</p><p id="CDR0000062763__1193">The Women’s Health Initiative (WHI) trial examined, as a secondary end point, the effect of combined estrogen-plus-progestin therapy and estrogen-only therapy on CRC incidence and mortality. Among women in the combined estrogen-plus-progestin group of the WHI, an extended follow-up (mean, 11.6 years) confirmed that fewer CRC were diagnosed in the combined hormone therapy group than in the placebo group (HR, 0.72; 95% CI, 0.56–0.94); the CRCs in women in the combined group were more likely to have lymph node involvement than the CRCs in women in the placebo group (50.5% vs. 28.6%; <i>P</i> < .001) and were classified at higher stages (regional and distant) (68.8% vs. 51.4%; <i>P</i> = .003). The number of CRC deaths in the combined group was higher than in the placebo group (37 vs. 27 deaths), but the difference was not statistically significant (HR, 1.29; 95% CI, 0.78–2.11).[<a class="bibr" href="#CDR0000062763_rl_1181_19" rid="CDR0000062763_rl_1181_19">19</a>]</p></div><div id="CDR0000062763__1194"><h3>Polyp Removal</h3><p id="CDR0000062763__1195">An analysis of data from the National Polyp Study (NPS), with external, historical controls, has commonly been cited to show a reduction of 76% to 90% in the subsequent incidence of CRC after colonoscopic polypectomy compared with three nonconcurrent, historical control groups.[<a class="bibr" href="#CDR0000062763_rl_1181_20" rid="CDR0000062763_rl_1181_20">20</a>] This study may be biased in several ways that inflate the apparent efficacy of polyp removal; the main problem is that potential enrollees in the NPS were excluded if they had CRC at their baseline examination. Because no such exclusions (or baseline colonoscopy examinations) were done in the three comparison groups, persons who had CRC at baseline would be counted as having incident CRC in subsequent follow-up. Although adjustments were attempted, it is not possible to know the magnitude of the impact of this problem on the result because it is not known how long CRC may be present without causing symptoms.</p><p id="CDR0000062763__1196">An additional long-term follow-up study (median follow-up, 15.8 years; maximum, 23 years) of the NPS cohort suggested an approximately 53% reduction in CRC mortality due to polypectomy (not just exclusion of persons with CRC at initial exam). However, the degree of reduction must be viewed with caution because this study did not have a direct comparison group, relying mainly on comparison to expected data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program. Further, details are not clear regarding factors that may have led to decreased mortality. Patients in the NPS were assigned to colonoscopy at years 1 and 3; colonoscopy was also offered to one of the two comparison groups at year 1; all participants were offered colonoscopy at year 6. However, following year 6, the exact surveillance that patients may have undergone and how that surveillance might have been associated with decreased CRC mortality were not well described.[<a class="bibr" href="#CDR0000062763_rl_1181_21" rid="CDR0000062763_rl_1181_21">21</a>]</p><p id="CDR0000062763__1197">It is expected that further follow-up in the United Kingdom Flexible Sigmoidoscopy Screening Trial will be able to provide more detail about the long-term effect of polypectomy, at least on the left side of the colon.[<a class="bibr" href="#CDR0000062763_rl_1181_21" rid="CDR0000062763_rl_1181_21">21</a>]</p><p id="CDR0000062763__1198">Other evidence about the benefit of sigmoidoscopy screening (at which time both polyps and early cancer would be removed) suggests that the impact of endoscopic screening, at least on the left side of the colon, is substantial and prolonged. In an RCT, 170,000 persons were randomly assigned to one-time sigmoidoscopy versus usual care. At sigmoidoscopy, polyps were removed, cancer was detected, and patients were referred for treatment. Based on sigmoidoscopy findings, persons were considered to have low risk if they had normal exams or only one or two small (<1 cm) tubular adenomas; such persons were not referred either for colonoscopy workup, or for colonoscopic surveillance. In a follow-up of 10 years, the left-sided CRC incidence in the low-risk group (about 95% of attendees were low risk) was 0.02% to 0.04% per year—a very low risk of CRC compared with average risk. The cause of reduced risk—whether due to detection and removal of large polyps or small ones, or selection of individuals at lower risk—is yet unclear.[<a class="bibr" href="#CDR0000062763_rl_1181_22" rid="CDR0000062763_rl_1181_22">22</a>] The natural history of large polyps is not well known, but some evidence suggests that such lesions become clinical CRC at a rate of approximately 1% per year.[<a class="bibr" href="#CDR0000062763_rl_1181_23" rid="CDR0000062763_rl_1181_23">23</a>] As a result of the strong data about the impact of endoscopy on the left colon, evidence from multiple studies has raised questions about the ability of endoscopy to reduce CRC mortality in the right colon.[<a class="bibr" href="#CDR0000062763_rl_1181_24" rid="CDR0000062763_rl_1181_24">24</a>-<a class="bibr" href="#CDR0000062763_rl_1181_26" rid="CDR0000062763_rl_1181_26">26</a>] Thus, it is unclear what the overall impact of endoscopy (e.g., colonoscopy screening) is, and whether there may be a large difference in impact on the left side of the colon compared with the right side.[<a class="bibr" href="#CDR0000062763_rl_1181_24" rid="CDR0000062763_rl_1181_24">24</a>]</p><p id="CDR0000062763__1199">Other studies suggest that the polyps with the greatest potential to progress to CRC are larger polyps (i.e., >1.0 cm), which include most of those with villous or high-grade histologic features. Retrospective cohort studies also show the harms associated with polypectomy, including bleeding.[<a class="bibr" href="#CDR0000062763_rl_1181_27" rid="CDR0000062763_rl_1181_27">27</a>,<a class="bibr" href="#CDR0000062763_rl_1181_28" rid="CDR0000062763_rl_1181_28">28</a>]</p></div><div id="CDR0000062763_rl_1181"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062763_rl_1181_1">Flossmann E, Rothwell PM; British Doctors Aspirin Trial and the UK-TIA Aspirin Trial: Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet 369 (9573): 1603-13, 2007. 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[<a href="https://pubmed.ncbi.nlm.nih.gov/7894320" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7894320</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1181_17">Gerhardsson de Verdier M, London S: Reproductive factors, exogenous female hormones, and colorectal cancer by subsite. Cancer Causes Control 3 (4): 355-60, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1617123" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1617123</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1181_18">Prihartono N, Palmer JR, Louik C, et al.: A case-control study of use of postmenopausal female hormone supplements in relation to the risk of large bowel cancer. Cancer Epidemiol Biomarkers Prev 9 (4): 443-7, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10794491" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10794491</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1181_19">Simon MS, Chlebowski RT, Wactawski-Wende J, et al.: Estrogen plus progestin and colorectal cancer incidence and mortality. J Clin Oncol 30 (32): 3983-90, 2012. [<a href="/pmc/articles/PMC3488271/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3488271</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23008295" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23008295</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1181_20">Winawer SJ, Zauber AG, Ho MN, et al.: Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 329 (27): 1977-81, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8247072" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8247072</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1181_21">Zauber AG, Winawer SJ, O'Brien MJ, et al.: Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med 366 (8): 687-96, 2012. [<a href="/pmc/articles/PMC3322371/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3322371</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22356322" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22356322</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1181_22">Atkin WS, Edwards R, Kralj-Hans I, et al.: Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet 375 (9726): 1624-33, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20430429" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20430429</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1181_23">Stryker SJ, Wolff BG, Culp CE, et al.: Natural history of untreated colonic polyps. Gastroenterology 93 (5): 1009-13, 1987. [<a href="https://pubmed.ncbi.nlm.nih.gov/3653628" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3653628</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1181_24">Brenner H, Chang-Claude J, Seiler CM, et al.: Protection from colorectal cancer after colonoscopy: a population-based, case-control study. Ann Intern Med 154 (1): 22-30, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/21200035" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21200035</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1181_25">Baxter NN, Goldwasser MA, Paszat LF, et al.: Association of colonoscopy and death from colorectal cancer. Ann Intern Med 150 (1): 1-8, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19075198" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19075198</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1181_26">Brenner H, Hoffmeister M, Arndt V, et al.: Protection from right- and left-sided colorectal neoplasms after colonoscopy: population-based study. J Natl Cancer Inst 102 (2): 89-95, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20042716" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20042716</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1181_27">Levin TR, Zhao W, Conell C, et al.: Complications of colonoscopy in an integrated health care delivery system. Ann Intern Med 145 (12): 880-6, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/17179057" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17179057</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1181_28">Warren JL, Klabunde CN, Mariotto AB, et al.: Adverse events after outpatient colonoscopy in the Medicare population. Ann Intern Med 150 (12): 849-57, W152, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19528563" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19528563</span></a>]</div></li></ol></div></div><div id="CDR0000062763__1200"><h2 id="_CDR0000062763__1200_">Factors With Inadequate Evidence of an Association With Colorectal Cancer</h2><div id="CDR0000062763__215"><h3>Nonsteroidal Anti-Inflammatory Drugs</h3><p id="CDR0000062763__1215">One large cohort study (301,240 people with 3,894 colorectal cancer [CRC] cases) found an association between daily or weekly nonaspirin (non-ASA) nonsteroidal anti-inflammatory drug (NSAID) use and reduced 10-year incidence of proximal and distal colon cancer, but not rectal cancer, with an HR of 0.67 (95% confidence interval [CI], 0.58–0.77) for daily use for colon cancer. Because exposure to non-ASA NSAIDs was assessed only once, assessment was by self-report, and there is no information on dose or duration of use, the certainty of this single study must be rated low. Further research is needed before this finding can be accepted.[<a class="bibr" href="#CDR0000062763_rl_1200_1" rid="CDR0000062763_rl_1200_1">1</a>]</p><p id="CDR0000062763__1209">Although evidence is currently inadequate to determine whether NSAIDs reduce CRC incidence, proponents suggest that any effect of these drugs results from their ability to inhibit the activity of cyclooxygenase (COX). COX is important in the transformation of arachidonic acid into prostanoids, prostaglandins, and thromboxane A2. NSAIDs include not only aspirin (ASA, which is considered separately here) and other, first-generation nonselective inhibitors of the two functional isoforms of COX, termed COX-1 and COX-2, but also newer second-generation drugs that inhibit primarily COX-2. Normally, COX-1 is expressed in most tissues and primarily plays a housekeeping role (e.g., gastrointestinal mucosal protection and platelet aggregation). COX-2 activity is crucial in stress responses and in mediating and propagating the pain and inflammation that are characteristic of arthritis.[<a class="bibr" href="#CDR0000062763_rl_1200_2" rid="CDR0000062763_rl_1200_2">2</a>]</p><p id="CDR0000062763__1216">Nonselective COX inhibitors include indomethacin (Indocin); sulindac (Clinoril); piroxicam (Feldene); diflunisal (Dolobid); ibuprofen (Advil, Motrin); ketoprofen (Orudis); naproxen (Naprosyn); and naproxen sodium (Aleve, Anaprox). Selective COX-2 inhibitors include celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra). Rofecoxib and valdecoxib are no longer marketed because of an associated increased risk of serious cardiovascular events. </p><p id="CDR0000062763__1213">Both celecoxib and rofecoxib have been associated with serious cardiovascular events including dose-related death from cardiovascular causes, myocardial infarction, stroke, or heart failure.[<a class="bibr" href="#CDR0000062763_rl_1200_3" rid="CDR0000062763_rl_1200_3">3</a>-<a class="bibr" href="#CDR0000062763_rl_1200_6" rid="CDR0000062763_rl_1200_6">6</a>] Four trials that demonstrated this increased risk are summarized in the <a href="/books/NBK65779/table/CDR0000062763__274/?report=objectonly" target="object" rid-ob="figobCDR0000062763274">Table 1</a>. In addition, a network meta-analysis of all large scale randomized controlled trials (RCTs) comparing any NSAID to any other NSAID or placebo found that there is little evidence to suggest that any of the investigated drugs are safe in terms of cardiovascular effects. Naproxen seemed least harmful.[<a class="bibr" href="#CDR0000062763_rl_1200_7" rid="CDR0000062763_rl_1200_7">7</a>]</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figCDR0000062763274"><a href="/books/NBK65779/table/CDR0000062763__274/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobCDR0000062763274"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="CDR0000062763__274"><a href="/books/NBK65779/table/CDR0000062763__274/?report=objectonly" target="object" rid-ob="figobCDR0000062763274">Table</a></h4><p class="float-caption no_bottom_margin">Table 1. Cardiovascular Risks Associated With Celecoxib and Rofecoxib Dose/Drugs. </p></div></div><p id="CDR0000062763__1214">Other major harms from all NSAIDs are gastrointestinal bleeding and renal impairment. The incidence of reported major gastrointestinal bleeding events appears to be dose-related.[<a class="bibr" href="#CDR0000062763_rl_1200_8" rid="CDR0000062763_rl_1200_8">8</a>]</p><p id="CDR0000062763__1217">Celecoxib reduces the incidence of adenomas; however, celecoxib does not have a clinical role in reducing the risk of sporadic CRC. Its long-term efficacy in preventing CRC has not been shown because of increased risk of cardiovascular events, and because there are other effective ways, such as screening to reduce CRC mortality.[<a class="bibr" href="#CDR0000062763_rl_1200_9" rid="CDR0000062763_rl_1200_9">9</a>] A population-based retrospective cohort study of nonaspirin NSAID use among individuals aged 65 years and older was associated with lower risk of CRC, particularly with longer durations of use.[<a class="bibr" href="#CDR0000062763_rl_1200_10" rid="CDR0000062763_rl_1200_10">10</a>]</p><p id="CDR0000062763__1218">Several rigorous studies have
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demonstrated the effectiveness of sulindac in reducing the size and number of
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adenomas in familial polyposis.[<a class="bibr" href="#CDR0000062763_rl_1200_11" rid="CDR0000062763_rl_1200_11">11</a>,<a class="bibr" href="#CDR0000062763_rl_1200_12" rid="CDR0000062763_rl_1200_12">12</a>] In a randomized, double-blind, placebo-controlled study of 77 patients with familial adenomatous polyposis, patients receiving 400 mg of celecoxib twice a day had a 28.0% reduction in the mean number of colorectal adenomas (<i>P</i> = .003 for the comparison with placebo) and a 30.7% reduction in the polyp burden (sum of polyp diameters; <i>P</i> = .001) as compared with reductions of 4.5% and 4.9%, respectively, in the placebo group. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9% (<i>P</i> = .33 for the comparison with placebo) and 14.6% (<i>P</i> = .09), respectively. The incidence of adverse events was similar among the groups.[<a class="bibr" href="#CDR0000062763_rl_1200_13" rid="CDR0000062763_rl_1200_13">13</a>]</p><p id="CDR0000062763__1219">The NSAID piroxicam, at a dose of 20 mg/day, reduced mean rectal prostaglandin
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concentration by 50% in individuals with a history of adenomas.[<a class="bibr" href="#CDR0000062763_rl_1200_14" rid="CDR0000062763_rl_1200_14">14</a>] Several
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studies assessing the effect of ASA or other nonsteroidals
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on polyp recurrence following polypectomy are in progress.[<a class="bibr" href="#CDR0000062763_rl_1200_15" rid="CDR0000062763_rl_1200_15">15</a>] In several of these studies,
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mucosal prostaglandin concentration is being measured.</p><p id="CDR0000062763__218">The potential for use of NSAIDs as a primary prevention measure is being
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studied. There are, however, several unresolved issues that preclude
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making general recommendations for their use. These include a paucity of
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knowledge about the proper dose and duration for these agents, and concern
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about whether the potential preventive benefits such as a reduction in the frequency or intensity of screening or surveillance could counterbalance long-term
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risks such as gastrointestinal ulceration and hemorrhagic stroke for the average-risk
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individual.[<a class="bibr" href="#CDR0000062763_rl_1200_16" rid="CDR0000062763_rl_1200_16">16</a>]</p></div><div id="CDR0000062763__1201"><h3>Calcium supplements</h3><p id="CDR0000062763__1202"> A randomized
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placebo-controlled trial tested the effect of calcium supplementation (3 g
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calcium carbonate daily [1,200 mg elemental calcium]) on the risk of recurrent
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adenoma.[<a class="bibr" href="#CDR0000062763_rl_1200_17" rid="CDR0000062763_rl_1200_17">17</a>] The primary end point was the proportion of patients (72% of whom
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were male) in whom at least one adenoma was detected following a first and/or
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second follow-up endoscopy. A modest decrease in risk was found for both
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developing at least one recurrent adenoma (adjusted risk ratio [ARR], 0.81; 95% CI,
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0.67–0.99) and in the average number of adenomas (ARR, 0.76;
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95% CI, 0.60–0.96). The investigators found the effect of calcium was similar
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across age, sex, and baseline dietary intake categories of calcium, fat, or
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fiber. The study was limited to individuals with a recent history of
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colorectal adenomas and could not determine the effect of calcium on risk of
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the first adenoma, nor was it large enough or of sufficient duration to examine
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the risk of invasive CRC. After calcium supplementation is stopped, the lower risk may persist up to 5 years.[<a class="bibr" href="#CDR0000062763_rl_1200_18" rid="CDR0000062763_rl_1200_18">18</a>] The results of other ongoing adenoma
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recurrence studies are awaited with interest. It is important to
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note that the dose of calcium salt administered may be important; the usual
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daily doses in trials have ranged from 1,250 to 2,000 mg of calcium.</p><p id="CDR0000062763__1203">In a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women, the administration of 500 mg of elemental calcium and 200 IU of vitamin D3 twice daily for an average of 7.0 years was not associated with a reduction in invasive CRC (HR, 1.08; 95% CI, 0.86–1.34; <i>P</i> = .051).[<a class="bibr" href="#CDR0000062763_rl_1200_19" rid="CDR0000062763_rl_1200_19">19</a>] The relatively short duration of follow-up, considering the latency period of CRC of 10 to 15 years, and suboptimal doses of calcium and vitamin D, may account for the negative effects of this trial, although other factors may also be responsible.[<a class="bibr" href="#CDR0000062763_rl_1200_20" rid="CDR0000062763_rl_1200_20">20</a>]</p></div><div id="CDR0000062763__1223"><h3>Dietary Factors</h3><div id="CDR0000062763__1224"><h4>Dietary fat and meat intake</h4><p id="CDR0000062763__1225">Colon cancer rates are high in populations with high total fat intakes and
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are lower in those consuming less fat.[<a class="bibr" href="#CDR0000062763_rl_1200_21" rid="CDR0000062763_rl_1200_21">21</a>] On average, fat comprises 40% to
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45% of total caloric intake in high-incidence Western countries; in low-risk
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populations, fat accounts for only 10% of dietary calories.[<a class="bibr" href="#CDR0000062763_rl_1200_22" rid="CDR0000062763_rl_1200_22">22</a>] Several case-control studies have explored the
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association of colon cancer risk with meat or fat consumption, as well as
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protein and energy intake.[<a class="bibr" href="#CDR0000062763_rl_1200_23" rid="CDR0000062763_rl_1200_23">23</a>,<a class="bibr" href="#CDR0000062763_rl_1200_24" rid="CDR0000062763_rl_1200_24">24</a>] Although positive associations with meat
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consumption or with fat intake have been found, the results have been inconsistent.[<a class="bibr" href="#CDR0000062763_rl_1200_25" rid="CDR0000062763_rl_1200_25">25</a>] A number of prospective
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cohort studies have been conducted in the United States and abroad; a systematic review of 13, including the Iowa Women’s Health Study and the Nurses’ Health Study, concluded that there appeared to be a positive association between meat consumption and CRC incidence. However, the authors noted that because only a few studies tried to investigate the independent effect of meat intake on cancer risk, the observed relationship might be attributed entirely to confounding.[<a class="bibr" href="#CDR0000062763_rl_1200_26" rid="CDR0000062763_rl_1200_26">26</a>] Similarly, a 2019 systematic review of observational studies, evaluating the association between processed or unprocessed red meat consumption and CRC incidence and mortality, concluded that a reduction of three servings per week resulted in very small to no decreases in those outcomes, although the certainty around these findings was judged low to very low.[<a class="bibr" href="#CDR0000062763_rl_1200_27" rid="CDR0000062763_rl_1200_27">27</a>] </p><p id="CDR0000062763__1226">A randomized controlled dietary modification study was undertaken among 48,835 postmenopausal women aged 50 to 79 years who were also enrolled in the WHI. The intervention promoted a goal of reducing total fat intake by 20%, while increasing daily intake of vegetables, fruits, and grains. The intervention group accomplished a reduction of fat intake of approximately 10% more than did the comparison group during the 8.1 years of follow-up. There was no evidence of reduction in invasive CRCs between the intervention and comparison groups with an HR of 1.08 (95% CI, 0.90–1.29).[<a class="bibr" href="#CDR0000062763_rl_1200_28" rid="CDR0000062763_rl_1200_28">28</a>] Likewise, there was no benefit of the low-fat diet on all-cancer mortality, overall mortality, or cardiovascular disease.[<a class="bibr" href="#CDR0000062763_rl_1200_29" rid="CDR0000062763_rl_1200_29">29</a>] This last observation was echoed in a 2019 systematic review of randomized controlled trials of the effect of variable red meat consumption on cancer outcomes. This review relied heavily on the WHI to reach the conclusion that there appears to be little to no effect of red meat intake on CRC incidence, although the certainty around this finding is low because of limitations in available studies.[<a class="bibr" href="#CDR0000062763_rl_1200_30" rid="CDR0000062763_rl_1200_30">30</a>]</p><p id="CDR0000062763__1227">Explanations for the conflicting results regarding whether dietary fat or
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meat intake affects the risk of CRC [<a class="bibr" href="#CDR0000062763_rl_1200_31" rid="CDR0000062763_rl_1200_31">31</a>] include the following:</p><ul id="CDR0000062763__1228"><li class="half_rhythm"><div>Validity of
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dietary questionnaires used.</div></li><li class="half_rhythm"><div>Differences in the average age of the
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population studied.</div></li><li class="half_rhythm"><div>Variations in methods of meat preparation (in some
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instances, mutagenic and carcinogenic heterocyclic amines could have been
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|
released at high temperatures).[<a class="bibr" href="#CDR0000062763_rl_1200_32" rid="CDR0000062763_rl_1200_32">32</a>]</div></li><li class="half_rhythm"><div>Variability in the consumption
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of other foods such as vegetables.[<a class="bibr" href="#CDR0000062763_rl_1200_33" rid="CDR0000062763_rl_1200_33">33</a>] </div></li><li class="half_rhythm"><div>Possible unadjusted bias from differential screening uptake between meat intake groups.</div></li></ul><p id="CDR0000062763__1229">Six case-control studies and two cohort studies have explored potential
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dietary risk factors for colorectal adenomas.[<a class="bibr" href="#CDR0000062763_rl_1200_34" rid="CDR0000062763_rl_1200_34">34</a>,<a class="bibr" href="#CDR0000062763_rl_1200_35" rid="CDR0000062763_rl_1200_35">35</a>] Three of the eight studies found that higher fat consumption was associated with increased
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risk. High fat intake has been found to increase the risk of adenoma
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recurrence following polypectomy.[<a class="bibr" href="#CDR0000062763_rl_1200_36" rid="CDR0000062763_rl_1200_36">36</a>] In a multicenter RCT, a diet low in fat (20% of total calories) and high in fiber,
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fruits, and vegetables did not reduce the risk of recurrence of colorectal
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adenomas.[<a class="bibr" href="#CDR0000062763_rl_1200_37" rid="CDR0000062763_rl_1200_37">37</a>]</p><p id="CDR0000062763__1230">Thus, the evidence is inadequate to determine whether reducing dietary fat and meat would reduce CRC incidence.</p></div></div><div id="CDR0000062763_rl_1200"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062763_rl_1200_1">Ruder EH, Laiyemo AO, Graubard BI, et al.: Non-steroidal anti-inflammatory drugs and colorectal cancer risk in a large, prospective cohort. Am J Gastroenterol 106 (7): 1340-50, 2011. [<a href="/pmc/articles/PMC3183504/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3183504</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21407185" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21407185</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_2">Hinz B, Brune K: Cyclooxygenase-2--10 years later. J Pharmacol Exp Ther 300 (2): 367-75, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11805193" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11805193</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_3">Kerr DJ, Dunn JA, Langman MJ, et al.: Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. N Engl J Med 357 (4): 360-9, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17652651" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17652651</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_4">Graham DJ, Campen D, Hui R, et al.: Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet 365 (9458): 475-81, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/15705456" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15705456</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_5">Bresalier RS, Sandler RS, Quan H, et al.: Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352 (11): 1092-102, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/15713943" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15713943</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_6">Solomon SD, McMurray JJ, Pfeffer MA, et al.: Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 352 (11): 1071-80, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/15713944" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15713944</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_7">Trelle S, Reichenbach S, Wandel S, et al.: Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ 342: c7086, 2011. 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7 (11 Suppl): 33-40, 1993.</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_16">Imperiale TF: Aspirin and the prevention of colorectal cancer. N Engl J Med 348 (10): 879-80, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12621130" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12621130</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_17">Baron JA, Beach M, Mandel JS, et al.: Calcium supplements for the prevention of colorectal adenomas. Calcium Polyp Prevention Study Group. N Engl J Med 340 (2): 101-7, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/9887161" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9887161</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_18">Grau MV, Baron JA, Sandler RS, et al.: Prolonged effect of calcium supplementation on risk of colorectal adenomas in a randomized trial. J Natl Cancer Inst 99 (2): 129-36, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17227996" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17227996</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_19">Wactawski-Wende J, Kotchen JM, Anderson GL, et al.: Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 354 (7): 684-96, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16481636" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16481636</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_20">Forman MR, Levin B: Calcium plus vitamin D3 supplementation and colorectal cancer in women. N Engl J Med 354 (7): 752-4, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16481644" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16481644</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_21">Rose DP, Boyar AP, Wynder EL: International comparisons of mortality rates for cancer of the breast, ovary, prostate, and colon, and per capita food consumption. Cancer 58 (11): 2363-71, 1986. [<a href="https://pubmed.ncbi.nlm.nih.gov/3768832" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3768832</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_22">Reddy BS: Dietary fat and its relationship to large bowel cancer. Cancer Res 41 (9 Pt 2): 3700-5, 1981. 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Cold Spring Harbor Laboratory, 1981, Branbury Report 7, 409-429.</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_27">Bjelke E: Epidemiology of colorectal cancer, with emphasis on diet. Int Congr Ser 484: 158-174, 1980.</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_28">Beresford SA, Johnson KC, Ritenbaugh C, et al.: Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 295 (6): 643-54, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16467233" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16467233</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_29">Howard BV, Van Horn L, Hsia J, et al.: Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 295 (6): 655-66, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16467234" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16467234</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_30">Zeraatkar D, Johnston BC, Bartoszko J, et al.: Effect of Lower Versus Higher Red Meat Intake on Cardiometabolic and Cancer Outcomes: A Systematic Review of Randomized Trials. Ann Intern Med 171 (10): 721-731, 2019. [<a href="https://pubmed.ncbi.nlm.nih.gov/31569236" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31569236</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_31">Goldbohm RA, van den Brandt PA, van 't Veer P, et al.: A prospective cohort study on the relation between meat consumption and the risk of colon cancer. Cancer Res 54 (3): 718-23, 1994. 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[<a href="https://pubmed.ncbi.nlm.nih.gov/2731998" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2731998</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_34">Neugut AI, Jacobson JS, DeVivo I: Epidemiology of colorectal adenomatous polyps. Cancer Epidemiol Biomarkers Prev 2 (2): 159-76, 1993 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/8467251" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8467251</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_35">Kampman E, Giovannucci E, van 't Veer P, et al.: Calcium, vitamin D, dairy foods, and the occurrence of colorectal adenomas among men and women in two prospective studies. Am J Epidemiol 139 (1): 16-29, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8296771" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8296771</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_36">Neugut AI, Garbowski GC, Lee WC, et al.: Dietary risk factors for the incidence and recurrence of colorectal adenomatous polyps. A case-control study. Ann Intern Med 118 (2): 91-5, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8416323" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8416323</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1200_37">Schatzkin A, Lanza E, Corle D, et al.: Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. N Engl J Med 342 (16): 1149-55, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10770979" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10770979</span></a>]</div></li></ol></div></div><div id="CDR0000062763__1275"><h2 id="_CDR0000062763__1275_">Factors and Interventions With Adequate Evidence of no Association With Colorectal Cancer</h2><div id="CDR0000062763__1205"><h3>Estrogen-Only Therapy </h3><p id="CDR0000062763__1206">The estrogen-only intervention component of the Women’s Health Initiative was conducted among women who had a hysterectomy, with colorectal cancer (CRC) incidence included as a secondary trial end point. CRC incidence was not decreased among women who had taken estrogens; after a median of 7.1 years of follow-up, 58 invasive cancers occurred in the estrogen arm compared with 53 invasive cancers in the placebo arm (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.77–1.63). Tumor stage and grade were similar in the two groups; deaths after CRC were 34% in the hormone group compared with 30% in the placebo group (HR, 1.34; 95% CI, 0.58–3.19).[<a class="bibr" href="#CDR0000062763_rl_1275_1" rid="CDR0000062763_rl_1275_1">1</a>]</p></div><div id="CDR0000062763__1207"><h3>Statins</h3><p id="CDR0000062763__1208">Overall, evidence indicates that statin use neither increases nor decreases the incidence or mortality of CRC. Although some case-control studies have shown a reduction in risk, neither a large cohort study [<a class="bibr" href="#CDR0000062763_rl_1275_2" rid="CDR0000062763_rl_1275_2">2</a>] nor a meta-analysis of four randomized controlled trials [<a class="bibr" href="#CDR0000062763_rl_1275_3" rid="CDR0000062763_rl_1275_3">3</a>] found any effect of statin use.</p></div><div id="CDR0000062763_rl_1275"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062763_rl_1275_1">Ritenbaugh C, Stanford JL, Wu L, et al.: Conjugated equine estrogens and colorectal cancer incidence and survival: the Women's Health Initiative randomized clinical trial. Cancer Epidemiol Biomarkers Prev 17 (10): 2609-18, 2008. [<a href="/pmc/articles/PMC2937217/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2937217</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18829444" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18829444</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1275_2">Jacobs EJ, Rodriguez C, Brady KA, et al.: Cholesterol-lowering drugs and colorectal cancer incidence in a large United States cohort. J Natl Cancer Inst 98 (1): 69-72, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16391373" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16391373</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062763_rl_1275_3">Dale KM, Coleman CI, Henyan NN, et al.: Statins and cancer risk: a meta-analysis. JAMA 295 (1): 74-80, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16391219" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16391219</span></a>]</div></li></ol></div></div><div id="CDR0000062763__86"><h2 id="_CDR0000062763__86_">Latest Updates to This Summary (10/30/2024)</h2><p id="CDR0000062763__88">The PDQ cancer information summaries are reviewed regularly and updated as
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new information becomes available. This section describes the latest
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changes made to this summary as of the date above.</p><p id="CDR0000062763__1288">
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<b>
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<a href="#CDR0000062763__1008">Incidence and Mortality</a>
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</b>
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</p><p id="CDR0000062763__1290">Revised <a href="#CDR0000062763__1162">text</a> to state that the overall 5-year survival rate is 65% for colorectal cancer (CRC), and about 4% of Americans are expected to develop CRC within their lifetimes.</p><p id="CDR0000062763__disclaimerHP_3">This summary is written and maintained by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/screening-prevention" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Screening and Prevention Editorial Board</a>, which is
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editorially independent of NCI. The summary reflects an independent review of
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the literature and does not represent a policy statement of NCI or NIH. More
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information about summary policies and the role of the PDQ Editorial Boards in
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maintaining the PDQ summaries can be found on the <a href="#CDR0000062763__AboutThis_1">About This PDQ Summary</a> and <a href="https://www.cancer.gov/publications/pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ® Cancer Information for Health Professionals</a> pages.
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</p></div><div id="CDR0000062763__AboutThis_1"><h2 id="_CDR0000062763__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000062763__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000062763__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about colorectal cancer prevention. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.</p></div><div id="CDR0000062763__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000062763__AboutThis_5">This summary is reviewed regularly and updated as necessary by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/screening-prevention" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Screening and Prevention Editorial Board</a>, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p><p id="CDR0000062763__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000062763__AboutThis_6"><li class="half_rhythm"><div>be discussed at a meeting,</div></li><li class="half_rhythm"><div>be cited with text, or</div></li><li class="half_rhythm"><div>replace or update an existing article that is already cited.</div></li></ul><p id="CDR0000062763__AboutThis_7">Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.</p><p id="CDR0000062763__AboutThis_9">Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.</p></div><div id="CDR0000062763__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000062763__AboutThis_11">Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Screening and Prevention Editorial Board uses a <a href="/books/n/pdqcis/CDR0000304747/?report=reader">formal evidence ranking system</a> in developing its level-of-evidence designations.</p></div><div id="CDR0000062763__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000062763__AboutThis_13">PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”</p><p id="CDR0000062763__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000062763__AboutThis_15">PDQ® Screening and Prevention Editorial Board. PDQ Colorectal Cancer Prevention. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: <a href="https://www.cancer.gov/types/colorectal/hp/colorectal-prevention-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www.cancer.gov/types/colorectal/hp/colorectal-prevention-pdq</a>. Accessed <MM/DD/YYYY>. [PMID: 26389222]</p><p id="CDR0000062763__AboutThis_16">Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in <a href="https://visualsonline.cancer.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Visuals Online</a>, a collection of over 2,000 scientific images.
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</p></div><div id="CDR0000062763__AboutThis_17"><h3>Disclaimer</h3><p id="CDR0000062763__AboutThis_19">The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the <a href="https://www.cancer.gov/about-cancer/managing-care" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Managing Cancer Care</a> page.</p></div><div id="CDR0000062763__AboutThis_20"><h3>Contact Us</h3><p id="CDR0000062763__AboutThis_21">More information about contacting us or receiving help with the Cancer.gov website can be found on our <a href="https://www.cancer.gov/contact" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Contact Us for Help</a> page. Questions can also be submitted to Cancer.gov through the website’s <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>.</p></div></div></div></div><div class="fm-sec"><h2 id="_NBK65779_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">PDQ Screening and Prevention Editorial Board</span>.</p><h3>Publication History</h3><p class="small">Published online: October 30, 2024.</p><h3>Version History</h3><ul class="simple-list" style="padding:0"><li><span class="bk_col_itm">NBK65779.22</span> October 30, 2024 (Displayed Version)</li><li><span class="bk_col_itm"><a href="/books/NBK65779.21/?report=reader">NBK65779.21</a></span> March 28, 2024</li><li><span class="bk_col_itm"><a href="/books/NBK65779.20/?report=reader">NBK65779.20</a></span> August 18, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK65779.19/?report=reader">NBK65779.19</a></span> May 24, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK65779.18/?report=reader">NBK65779.18</a></span> April 26, 2023</li><li><span class="bk_col_itm"><a href="/books/NBK65779.17/?report=reader">NBK65779.17</a></span> April 21, 2022</li><li><span class="bk_col_itm"><a href="/books/NBK65779.16/?report=reader">NBK65779.16</a></span> June 29, 2021</li><li><span class="bk_col_itm"><a href="/books/NBK65779.15/?report=reader">NBK65779.15</a></span> March 29, 2021</li><li><span class="bk_col_itm"><a href="/books/NBK65779.14/?report=reader">NBK65779.14</a></span> February 28, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK65779.13/?report=reader">NBK65779.13</a></span> February 13, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK65779.12/?report=reader">NBK65779.12</a></span> December 13, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65779.11/?report=reader">NBK65779.11</a></span> April 16, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65779.10/?report=reader">NBK65779.10</a></span> March 14, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65779.9/?report=reader">NBK65779.9</a></span> March 1, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK65779.8/?report=reader">NBK65779.8</a></span> May 12, 2017</li><li><span class="bk_col_itm"><a href="/books/NBK65779.7/?report=reader">NBK65779.7</a></span> February 3, 2017</li><li><span class="bk_col_itm"><a href="/books/NBK65779.6/?report=reader">NBK65779.6</a></span> December 27, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK65779.5/?report=reader">NBK65779.5</a></span> December 8, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK65779.4/?report=reader">NBK65779.4</a></span> October 21, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK65779.3/?report=reader">NBK65779.3</a></span> February 11, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK65779.2/?report=reader">NBK65779.2</a></span> October 27, 2015</li><li><span class="bk_col_itm"><a href="/books/NBK65779.1/?report=reader">NBK65779.1</a></span> February 13, 2015</li></ul><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="http://www.cancer.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Cancer Institute (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>PDQ Screening and Prevention Editorial Board. Colorectal Cancer Prevention (PDQ®): Health Professional Version. 2024 Oct 30. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobCDR0000062763274"><div id="CDR0000062763__274" class="table"><h3><span class="title">Table 1. Cardiovascular Risks Associated With Celecoxib and Rofecoxib Dose/Drugs</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65779/table/CDR0000062763__274/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062763__274_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="vertical-align:top;">Authors</th><th colspan="1" rowspan="1" style="vertical-align:top;">Dose/Trial Drug</th><th colspan="1" rowspan="1" style="vertical-align:top;">Risk</th><th colspan="1" rowspan="1" style="vertical-align:top;">Study Type</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">[<a class="bibr" href="#CDR0000062763_rl_1200_4" rid="CDR0000062763_rl_1200_4">4</a>] </td><td colspan="1" rowspan="1" style="vertical-align:top;">Rofecoxib <25 mg/qd; rofecoxib >25 mg/qd
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">OR, 1.47 (0.99–2.17) vs. 3.58 (1.27–10.17)
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Nested case-control study all users</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">[<a class="bibr" href="#CDR0000062763_rl_1200_6" rid="CDR0000062763_rl_1200_6">6</a>] </td><td colspan="1" rowspan="1" style="vertical-align:top;">Celecoxib
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200 mg/qd vs. 400 mg bid</td><td colspan="1" rowspan="1" style="vertical-align:top;">3.4%; HR, 3.4 (95% CI, 1.4–7.8)</td><td colspan="1" rowspan="1" style="vertical-align:top;">Sporadic adenoma prevention trial (N = 2,035)</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">
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[<a class="bibr" href="#CDR0000062763_rl_1200_5" rid="CDR0000062763_rl_1200_5">5</a>]
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</td><td colspan="1" rowspan="1" style="vertical-align:top;">Rofecoxib 25 mg/qd</td><td colspan="1" rowspan="1" style="vertical-align:top;">RR, 1.92 (95% CI, 1.19–3.11; <i>P</i> = .008)</td><td colspan="1" rowspan="1" style="vertical-align:top;">Chemoprevention
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of sporadic adenoma</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">[<a class="bibr" href="#CDR0000062763_rl_1200_3" rid="CDR0000062763_rl_1200_3">3</a>] </td><td colspan="1" rowspan="1" style="vertical-align:top;">Rofecoxib 25 mg/qd</td><td colspan="1" rowspan="1" style="vertical-align:top;">RR (estimated), 2.66 (95% CI, 1.03–6.86; <i>P</i> = .04)</td><td colspan="1" rowspan="1" style="vertical-align:top;">Chemoprevention of sporadic adenoma; median study Rx 7.4 months</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">bid = twice a day; qd = every day; CI = confidence interval; HR = hazard ratio; OR = odds ratio; RR = relative risk; Rx = prescription.</p></div></dd></dl></dl></div></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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