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Pancreatic cancer, susceptibility to, 4(PNCA4)

MedGen UID:
482072
•Concept ID:
C3280442
•
Finding
Synonym: Pancreatic cancer 4
 
Gene (location): BRCA1 (17q21.31)
 
Monarch Initiative: MONDO:0013685
OMIM®: 614320

Disease characteristics

Excerpted from the GeneReview: BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer
BRCA1- and BRCA2-associated hereditary breast and ovarian cancer (HBOC) is characterized by an increased risk for female and male breast cancer, ovarian cancer (including fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma primarily in individuals with a BRCA2 pathogenic variant. The risk of developing an associated cancer varies depending on whether HBOC is caused by a BRCA1 or BRCA2 pathogenic variant. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Nancie Petrucelli  |  Mary B Daly  |  Tuya Pal   view full author information

Professional guidelines

PubMed

Second Primary Cancer Risks After Breast Cancer in BRCA1 and BRCA2 Pathogenic Variant Carriers.
Allen I, Hassan H, Walburga Y, Huntley C, Loong L, Rahman T, Allen S, Garrett A, Torr B, Bacon A, Knott C, Jose S, Vernon S, Lüchtenborg M, Pethick J, Santaniello F, Goel S, Wang YW, Lavelle K, McRonald F, Eccles D, Morris E, Hardy S, Turnbull C, Tischkowitz M, Pharoah P, Antoniou AC
J Clin Oncol 2025 Feb 20;43(6):651-661. Epub 2024 Oct 29 doi: 10.1200/JCO.24.01146. PMID: 39475295Free PMC Article
Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion.
Stoffel EM, McKernin SE, Brand R, Canto M, Goggins M, Moravek C, Nagarajan A, Petersen GM, Simeone DM, Yurgelun M, Khorana AA
J Clin Oncol 2019 Jan 10;37(2):153-164. Epub 2018 Nov 20 doi: 10.1200/JCO.18.01489. PMID: 30457921
Familial pancreatic cancer: Concept, management and issues.
Matsubayashi H, Takaori K, Morizane C, Maguchi H, Mizuma M, Takahashi H, Wada K, Hosoi H, Yachida S, Suzuki M, Usui R, Furukawa T, Furuse J, Sato T, Ueno M, Kiyozumi Y, Hijioka S, Mizuno N, Terashima T, Mizumoto M, Kodama Y, Torishima M, Kawaguchi T, Ashida R, Kitano M, Hanada K, Furukawa M, Kawabe K, Majima Y, Shimosegawa T
World J Gastroenterol 2017 Feb 14;23(6):935-948. doi: 10.3748/wjg.v23.i6.935. PMID: 28246467Free PMC Article

Curated

UK NICE Clinical Guideline CG164, Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer, 2023

American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, BRCA1 and BRCA2 Pathogenic Variants (Hereditary Breast and Ovarian Cancer), 2019

Recent clinical studies

Etiology

Smoking, alcohol consumption, and 24 gastrointestinal diseases: Mendelian randomization analysis.
Yuan S, Chen J, Ruan X, Sun Y, Zhang K, Wang X, Li X, Gill D, Burgess S, Giovannucci E, Larsson SC
Elife 2023 Feb 2;12 doi: 10.7554/eLife.84051. PMID: 36727839Free PMC Article
Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants.
Li S, Silvestri V, Leslie G, Rebbeck TR, Neuhausen SL, Hopper JL, Nielsen HR, Lee A, Yang X, McGuffog L, Parsons MT, Andrulis IL, Arnold N, Belotti M, Borg Å, Buecher B, Buys SS, Caputo SM, Chung WK, Colas C, Colonna SV, Cook J, Daly MB, de la Hoya M, de Pauw A, Delhomelle H, Eason J, Engel C, Evans DG, Faust U, Fehm TN, Fostira F, Fountzilas G, Frone M, Garcia-Barberan V, Garre P, Gauthier-Villars M, Gehrig A, Glendon G, Goldgar DE, Golmard L, Greene MH, Hahnen E, Hamann U, Hanson H, Hassan T, Hentschel J, Horvath J, Izatt L, Janavicius R, Jiao Y, John EM, Karlan BY, Kim SW, Konstantopoulou I, Kwong A, Laugé A, Lee JW, Lesueur F, Mebirouk N, Meindl A, Mouret-Fourme E, Musgrave H, Ngeow Yuen Yie J, Niederacher D, Park SK, Pedersen IS, Ramser J, Ramus SJ, Rantala J, Rashid MU, Reichl F, Ritter J, Rump A, Santamariña M, Saule C, Schmidt G, Schmutzler RK, Senter L, Shariff S, Singer CF, Southey MC, Stoppa-Lyonnet D, Sutter C, Tan Y, Teo SH, Terry MB, Thomassen M, Tischkowitz M, Toland AE, Torres D, Vega A, Wagner SA, Wang-Gohrke S, Wappenschmidt B, Weber BHF, Yannoukakos D, Spurdle AB, Easton DF, Chenevix-Trench G, Ottini L, Antoniou AC
J Clin Oncol 2022 May 10;40(14):1529-1541. Epub 2022 Jan 25 doi: 10.1200/JCO.21.02112. PMID: 35077220Free PMC Article
Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer.
Hu C, Hart SN, Polley EC, Gnanaolivu R, Shimelis H, Lee KY, Lilyquist J, Na J, Moore R, Antwi SO, Bamlet WR, Chaffee KG, DiCarlo J, Wu Z, Samara R, Kasi PM, McWilliams RR, Petersen GM, Couch FJ
JAMA 2018 Jun 19;319(23):2401-2409. doi: 10.1001/jama.2018.6228. PMID: 29922827Free PMC Article
Pancreatic cancer.
Vincent A, Herman J, Schulick R, Hruban RH, Goggins M
Lancet 2011 Aug 13;378(9791):607-20. Epub 2011 May 26 doi: 10.1016/S0140-6736(10)62307-0. PMID: 21620466Free PMC Article
Familial pancreatic cancer.
Jørgensen MT, Mortensen MB, Gerdes AM, De Muckadell OB
Scand J Gastroenterol 2008;43(4):387-97. doi: 10.1080/00365520701775229. PMID: 18365902

Diagnosis

Expansion of Cancer Risk Profile for BRCA1 and BRCA2 Pathogenic Variants.
Momozawa Y, Sasai R, Usui Y, Shiraishi K, Iwasaki Y, Taniyama Y, Parsons MT, Mizukami K, Sekine Y, Hirata M, Kamatani Y, Endo M, Inai C, Takata S, Ito H, Kohno T, Matsuda K, Nakamura S, Sugano K, Yoshida T, Nakagawa H, Matsuo K, Murakami Y, Spurdle AB, Kubo M
JAMA Oncol 2022 Jun 1;8(6):871-878. doi: 10.1001/jamaoncol.2022.0476. PMID: 35420638Free PMC Article
Genetic characterization of pancreatic cancer patients and prediction of carrier status of germline pathogenic variants in cancer-predisposing genes.
Mizukami K, Iwasaki Y, Kawakami E, Hirata M, Kamatani Y, Matsuda K, Endo M, Sugano K, Yoshida T, Murakami Y, Nakagawa H, Spurdle AB, Momozawa Y
EBioMedicine 2020 Oct;60:103033. Epub 2020 Sep 24 doi: 10.1016/j.ebiom.2020.103033. PMID: 32980694Free PMC Article
Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer.
Hu C, Hart SN, Polley EC, Gnanaolivu R, Shimelis H, Lee KY, Lilyquist J, Na J, Moore R, Antwi SO, Bamlet WR, Chaffee KG, DiCarlo J, Wu Z, Samara R, Kasi PM, McWilliams RR, Petersen GM, Couch FJ
JAMA 2018 Jun 19;319(23):2401-2409. doi: 10.1001/jama.2018.6228. PMID: 29922827Free PMC Article
Pancreatic cancer.
Vincent A, Herman J, Schulick R, Hruban RH, Goggins M
Lancet 2011 Aug 13;378(9791):607-20. Epub 2011 May 26 doi: 10.1016/S0140-6736(10)62307-0. PMID: 21620466Free PMC Article
Familial pancreatic cancer.
Jørgensen MT, Mortensen MB, Gerdes AM, De Muckadell OB
Scand J Gastroenterol 2008;43(4):387-97. doi: 10.1080/00365520701775229. PMID: 18365902

Therapy

Plasma metabolites as mediators in immune cell-pancreatic cancer risk: insights from Mendelian randomization.
Zhang K, Zhu J, Wang P, Chen Y, Wang Z, Ge X, Wu J, Chen L, Lu Y, Xu P, Yao J
Front Immunol 2024;15:1402113. Epub 2024 Jun 12 doi: 10.3389/fimmu.2024.1402113. PMID: 38933268Free PMC Article
NRDE2 deficiency impairs homologous recombination repair and sensitizes hepatocellular carcinoma to PARP inhibitors.
Wang Y, Liu X, Zuo X, Wang C, Zhang Z, Zhang H, Zeng T, Chen S, Liu M, Chen H, Song Q, Li Q, Yang C, Le Y, Xing J, Zhang H, An J, Jia W, Kang L, Zhang H, Xie H, Ye J, Wu T, He F, Zhang X, Li Y, Zhou G
Cell Genom 2024 May 8;4(5):100550. Epub 2024 May 1 doi: 10.1016/j.xgen.2024.100550. PMID: 38697125Free PMC Article
Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization.
King SD, Veliginti S, Brouwers MCGJ, Ren Z, Zheng W, Setiawan VW, Wilkens LR, Shu XO, Arslan AA, Beane Freeman LE, Bracci PM, Canzian F, Du M, Gallinger SJ, Giles GG, Goodman PJ, Haiman CA, Kogevinas M, Kooperberg C, LeMarchand L, Neale RE, Visvanathan K, White E, Albanes D, Andreotti G, Babic A, Berndt SI, Brais LK, Brennan P, Buring JE, Rabe KG, Bamlet WR, Chanock SJ, Fuchs CS, Gaziano JM, Giovannucci EL, Hackert T, Hassan MM, Katzke V, Kurtz RC, Lee IM, Malats N, Murphy N, Oberg AL, Orlow I, Porta M, Real FX, Rothman N, Sesso HD, Silverman DT, Thompson IM, Wactawski-Wende J, Wang X, Wentzensen N, Yu H, Zeleniuch-Jacquotte A, Yu K, Wolpin BM, Duell EJ, Li D, Hung RJ, Perdomo S, McCullough ML, Freedman ND, Patel AV, Peters U, Riboli E, Sund M, Tjønneland A, Zhong J, Van Den Eeden SK, Kraft P, Risch HA, Amundadottir LT, Klein AP, Stolzenberg-Solomon RZ, Antwi SO
Cancer Epidemiol Biomarkers Prev 2023 Sep 1;32(9):1265-1269. doi: 10.1158/1055-9965.EPI-23-0453. PMID: 37351909Free PMC Article
Smoking, alcohol consumption, and 24 gastrointestinal diseases: Mendelian randomization analysis.
Yuan S, Chen J, Ruan X, Sun Y, Zhang K, Wang X, Li X, Gill D, Burgess S, Giovannucci E, Larsson SC
Elife 2023 Feb 2;12 doi: 10.7554/eLife.84051. PMID: 36727839Free PMC Article
The Role of Obesity, Type 2 Diabetes, and Metabolic Factors in Pancreatic Cancer: A Mendelian Randomization Study.
Carreras-Torres R, Johansson M, Gaborieau V, Haycock PC, Wade KH, Relton CL, Martin RM, Davey Smith G, Brennan P
J Natl Cancer Inst 2017 Sep 1;109(9) doi: 10.1093/jnci/djx012. PMID: 28954281Free PMC Article

Prognosis

Smoking, alcohol consumption, and 24 gastrointestinal diseases: Mendelian randomization analysis.
Yuan S, Chen J, Ruan X, Sun Y, Zhang K, Wang X, Li X, Gill D, Burgess S, Giovannucci E, Larsson SC
Elife 2023 Feb 2;12 doi: 10.7554/eLife.84051. PMID: 36727839Free PMC Article
Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer.
Alam A, Levanduski E, Denz P, Villavicencio HS, Bhatta M, Alhorebi L, Zhang Y, Gomez EC, Morreale B, Senchanthisai S, Li J, Turowski SG, Sexton S, Sait SJ, Singh PK, Wang J, Maitra A, Kalinski P, DePinho RA, Wang H, Liao W, Abrams SI, Segal BH, Dey P
Cancer Cell 2022 Feb 14;40(2):153-167.e11. Epub 2022 Feb 3 doi: 10.1016/j.ccell.2022.01.003. PMID: 35120601Free PMC Article
Genetic characterization of pancreatic cancer patients and prediction of carrier status of germline pathogenic variants in cancer-predisposing genes.
Mizukami K, Iwasaki Y, Kawakami E, Hirata M, Kamatani Y, Matsuda K, Endo M, Sugano K, Yoshida T, Murakami Y, Nakagawa H, Spurdle AB, Momozawa Y
EBioMedicine 2020 Oct;60:103033. Epub 2020 Sep 24 doi: 10.1016/j.ebiom.2020.103033. PMID: 32980694Free PMC Article
Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families.
Yang X, Leslie G, Doroszuk A, Schneider S, Allen J, Decker B, Dunning AM, Redman J, Scarth J, Plaskocinska I, Luccarini C, Shah M, Pooley K, Dorling L, Lee A, Adank MA, Adlard J, Aittomäki K, Andrulis IL, Ang P, Barwell J, Bernstein JL, Bobolis K, Borg Å, Blomqvist C, Claes KBM, Concannon P, Cuggia A, Culver JO, Damiola F, de Pauw A, Diez O, Dolinsky JS, Domchek SM, Engel C, Evans DG, Fostira F, Garber J, Golmard L, Goode EL, Gruber SB, Hahnen E, Hake C, Heikkinen T, Hurley JE, Janavicius R, Kleibl Z, Kleiblova P, Konstantopoulou I, Kvist A, Laduca H, Lee ASG, Lesueur F, Maher ER, Mannermaa A, Manoukian S, McFarland R, McKinnon W, Meindl A, Metcalfe K, Mohd Taib NA, Moilanen J, Nathanson KL, Neuhausen S, Ng PS, Nguyen-Dumont T, Nielsen SM, Obermair F, Offit K, Olopade OI, Ottini L, Penkert J, Pylkäs K, Radice P, Ramus SJ, Rudaitis V, Side L, Silva-Smith R, Silvestri V, Skytte AB, Slavin T, Soukupova J, Tondini C, Trainer AH, Unzeitig G, Usha L, van Overeem Hansen T, Whitworth J, Wood M, Yip CH, Yoon SY, Yussuf A, Zogopoulos G, Goldgar D, Hopper JL, Chenevix-Trench G, Pharoah P, George SHL, Balmaña J, Houdayer C, James P, El-Haffaf Z, Ehrencrona H, Janatova M, Peterlongo P, Nevanlinna H, Schmutzler R, Teo SH, Robson M, Pal T, Couch F, Weitzel JN, Elliott A, Southey M, Winqvist R, Easton DF, Foulkes WD, Antoniou AC, Tischkowitz M
J Clin Oncol 2020 Mar 1;38(7):674-685. Epub 2019 Dec 16 doi: 10.1200/JCO.19.01907. PMID: 31841383Free PMC Article
Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer.
Hu C, Hart SN, Polley EC, Gnanaolivu R, Shimelis H, Lee KY, Lilyquist J, Na J, Moore R, Antwi SO, Bamlet WR, Chaffee KG, DiCarlo J, Wu Z, Samara R, Kasi PM, McWilliams RR, Petersen GM, Couch FJ
JAMA 2018 Jun 19;319(23):2401-2409. doi: 10.1001/jama.2018.6228. PMID: 29922827Free PMC Article

Clinical prediction guides

Smoking, alcohol consumption, and 24 gastrointestinal diseases: Mendelian randomization analysis.
Yuan S, Chen J, Ruan X, Sun Y, Zhang K, Wang X, Li X, Gill D, Burgess S, Giovannucci E, Larsson SC
Elife 2023 Feb 2;12 doi: 10.7554/eLife.84051. PMID: 36727839Free PMC Article
Expansion of Cancer Risk Profile for BRCA1 and BRCA2 Pathogenic Variants.
Momozawa Y, Sasai R, Usui Y, Shiraishi K, Iwasaki Y, Taniyama Y, Parsons MT, Mizukami K, Sekine Y, Hirata M, Kamatani Y, Endo M, Inai C, Takata S, Ito H, Kohno T, Matsuda K, Nakamura S, Sugano K, Yoshida T, Nakagawa H, Matsuo K, Murakami Y, Spurdle AB, Kubo M
JAMA Oncol 2022 Jun 1;8(6):871-878. doi: 10.1001/jamaoncol.2022.0476. PMID: 35420638Free PMC Article
Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer.
Alam A, Levanduski E, Denz P, Villavicencio HS, Bhatta M, Alhorebi L, Zhang Y, Gomez EC, Morreale B, Senchanthisai S, Li J, Turowski SG, Sexton S, Sait SJ, Singh PK, Wang J, Maitra A, Kalinski P, DePinho RA, Wang H, Liao W, Abrams SI, Segal BH, Dey P
Cancer Cell 2022 Feb 14;40(2):153-167.e11. Epub 2022 Feb 3 doi: 10.1016/j.ccell.2022.01.003. PMID: 35120601Free PMC Article
Genetic characterization of pancreatic cancer patients and prediction of carrier status of germline pathogenic variants in cancer-predisposing genes.
Mizukami K, Iwasaki Y, Kawakami E, Hirata M, Kamatani Y, Matsuda K, Endo M, Sugano K, Yoshida T, Murakami Y, Nakagawa H, Spurdle AB, Momozawa Y
EBioMedicine 2020 Oct;60:103033. Epub 2020 Sep 24 doi: 10.1016/j.ebiom.2020.103033. PMID: 32980694Free PMC Article
Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer.
Hu C, Hart SN, Polley EC, Gnanaolivu R, Shimelis H, Lee KY, Lilyquist J, Na J, Moore R, Antwi SO, Bamlet WR, Chaffee KG, DiCarlo J, Wu Z, Samara R, Kasi PM, McWilliams RR, Petersen GM, Couch FJ
JAMA 2018 Jun 19;319(23):2401-2409. doi: 10.1001/jama.2018.6228. PMID: 29922827Free PMC Article

Recent systematic reviews

Germline pathogenic variants in the MRE11, RAD50, and NBN (MRN) genes in cancer predisposition: A systematic review and meta-analysis.
Stastna B, Dolezalova T, Matejkova K, Nemcova B, Zemankova P, Janatova M, Kleiblova P, Soukupova J, Kleibl Z
Int J Cancer 2024 Nov 1;155(9):1604-1615. Epub 2024 Jun 26 doi: 10.1002/ijc.35066. PMID: 38924040
A systematic review and network meta-analysis of single nucleotide polymorphisms associated with pancreatic cancer risk.
Ye ZM, Li LJ, Luo MB, Qing HY, Zheng JH, Zhang C, Lu YX, Tang YM
Aging (Albany NY) 2020 Nov 20;12(24):25256-25274. doi: 10.18632/aging.104128. PMID: 33226370Free PMC Article
Association between GSTT1 Homozygous Deletion and Risk of Pancreatic Cancer: A Meta Analysis.
Cui JP, Lin MY, Liu ZH, Liu BL
Chin Med Sci J 2019 Sep 30;34(3):205-210. doi: 10.24920/003490. PMID: 31648673
Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion.
Stoffel EM, McKernin SE, Brand R, Canto M, Goggins M, Moravek C, Nagarajan A, Petersen GM, Simeone DM, Yurgelun M, Khorana AA
J Clin Oncol 2019 Jan 10;37(2):153-164. Epub 2018 Nov 20 doi: 10.1200/JCO.18.01489. PMID: 30457921
Screening for pancreatic cancer in familial high-risk individuals: A systematic review.
Lu C, Xu CF, Wan XY, Zhu HT, Yu CH, Li YM
World J Gastroenterol 2015 Jul 28;21(28):8678-86. doi: 10.3748/wjg.v21.i28.8678. PMID: 26229410Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NICE, 2023
      UK NICE Clinical Guideline CG164, Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer, 2023
    • ACMG ACT, 2019
      American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, BRCA1 and BRCA2 Pathogenic Variants (Hereditary Breast and Ovarian Cancer), 2019

    Reviews

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