1469 lines
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<h1 class="page-title">Rare Finding in All of Us Data Affects DNA Testing for Certain Cancer Drugs</h1>
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<h2><strong>Key Points</strong></h2>
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<ul>
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<li>Changes, or <a href="https://medlineplus.gov/genetics/understanding/genomicresearch/pharmacogenomics">variants, in a person’s DNA</a> can affect how cancer medicines (chemotherapies) work for them.</li>
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<li><a href="https://medlineplus.gov/genetics/understanding/testing/genetictesting/">DNA testing</a> can be used to help determine how much chemotherapy to give to a person with cancer.</li>
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<li><em>All of Us</em> researchers have uncovered instances when a certain DNA test for chemotherapy use might not work as expected.</li>
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<h2>In short</h2>
|
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<p><strong>Thanks to data </strong><strong>from <em>All of Us </em>participants, DNA testing for using certain chemotherapies can be made more reliable.</strong></p>
|
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<p>There are currently more than 100 chemotherapies to treat cancer. For each patient, health care providers must decide which chemotherapy to use and how much. Too much could be dangerous, and too little might not work.</p>
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<p>Health care providers look at variants in the <em>DPYD</em> gene before they prescribe two common chemotherapies. <strong>Findings from a project that studied <em>All of Us </em>data led to an updated recommendation for <em>DPYD </em>gene testing for chemotherapy use. </strong>The results were published in the journal <a href="https://pubmed.ncbi.nlm.nih.gov/38129972/"><em>Clinical and Translational Science</em></a>.</p>
|
||
<h2><em>DPYD</em> and Cancer Treatment</h2>
|
||
<p>Many <em>DPYD </em>gene variants can affect how someone reacts to chemotherapies called 5-fluorouracil (5-FU) and capecitabine. This study looked at two particular <em>DPYD </em>gene variants.</p>
|
||
<p>One of the two variants is “active.” It affects how the body reacts to the chemotherapy. If someone has this active variant, they are more sensitive to the medicine. Receiving the typical dose could be dangerous. So a health care provider would give them a lower dose to safely treat their cancer.</p>
|
||
<p>Because the active variant is hard to test for, many labs look for an alternate variant in the same gene. This variant is easy to detect with common DNA tests. However, it does not affect how the body reacts to chemotherapy. The labs use the alternate variant to represent the presence of the active variant, because earlier research showed they always occurred together.</p>
|
||
<p><strong>However, this research study showed that the two variants do not always occur together. </strong>The researchers learned about a hospital patient who had the alternate variant but <em>not </em>the active variant. <strong>To find out how common it is for these variants to occur separately, the research team turned to <em>All of Us</em>.</strong></p>
|
||
<h2><em><em>All of Us</em></em> Data Reveals Rare Cases</h2>
|
||
<p>The researchers looked at DNA data from more than 245,000 <em>All of Us </em>participants. <strong>They found 14 more people who had the alternate <em>DPYD </em>gene variant but not the active variant.</strong></p>
|
||
<p>Having only one of the two <em>DPYD </em>gene variants is rare but very important for the people in which it occurs. If the testing they receive looks for only the alternate variant, they may get a lower dose of chemotherapy. But because they don’t have the active variant, they may be able to handle the regular dose, which could better treat the cancer.</p>
|
||
<p><strong>In response to this study, experts changed the </strong><a href="https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/"><strong>guideline</strong></a><strong> that providers follow for <em>DPYD </em>gene testing for chemotherapy use.</strong> The guideline now recommends that labs test directly for the active <em>DPYD </em>gene variant. And if they test for only the alternate variant, they need to tell the patients so.</p>
|
||
<p>This study shows the power of <em>All of Us </em>data for precision medicine research. <em>All of Us </em>has one of the largest genomic datasets of its kind for health research. <strong>Because so many participants have shared samples for DNA data, researchers can discover rare occurrences like these.</strong></p>
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<p>There is still more to learn about DNA changes that affect medical treatment — and <em>All of Us </em>can help.</p>
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Conduct research with All of Us
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Exploring Polygenic Risk Scores Using <em class="aou-text">All of Us</em>
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<img src="/sites/default/files/MicrosoftTeams-image%20%2859%29.png" width="900" height="900" alt="Birthplace linked to cancer risk in Hispanic communities. Liver cancer rates were nearly twice as high for participants born outside the U.S. Logo of the All of Us Research Program. Illustration of a globe showing the Western Hemisphere with location pins in both North and South America." loading="lazy" typeof="foaf:Image" class="img-fluid" />
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Study Links Birthplace and Cancer Risk Among Hispanic <em class="aou-text">All of Us</em> Participants
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