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Cancer risks in Jewish male BRCA1 and BRCA2 mutation carriers

  • Epidemiology
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Abstract

Cancer risks and tumor types in male BRCA1 and BRCA2 mutation carriers are still unsettled. Cancer risks in men who were found to harbor a BRCA1 (n = 150) or a BRCA2 (n = 88) mutation or both (n = 2) were assessed by cross referencing with data on cancer occurrence in the Israeli National Cancer Registry. Incidence rates in mutation carriers were compared with men who were counseled, genotyped, and found not to harbor the familial mutation (true negative n = 122), and with standardized incidence rates (SIRs). Of 210 cancer-free individuals at initial counseling, 11 cancers were diagnosed after a mean follow-up of 5.06 ± 4.1 years (1064 person/years) compared with 1/122 in a BRCA true-negative man. The SIR for all BRCA1/2 mutation carriers compared with the rates in the general population were elevated for pancreatic cancer [2.97 (95 % CI 1.83–4.29)] and breast cancer [16.44 (95 % CI 9.65–26.24)]. For prostate cancer these rates were 0.59 (95 % CI 0.4–0.84). Jewish BRCA1/2 mutation carriers are at an increased risk for breast and pancreatic, but not prostate cancer. These cancer risks and the consequent recommendations, if validated, should be transmitted to carriers at test result disclosure.

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References

  1. Shuen AY, Foulkes WD (2011) Inherited mutations in breast cancer genes–risk and response. J Mammary Gland Biol Neoplasia 16(1):3–15. doi:10.1007/s10911-011-9213-5

    Article  PubMed  Google Scholar 

  2. Breast Cancer Linkage Consortium (1999) Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 91(15):1310–1316

    Article  Google Scholar 

  3. Edwards SM, Kote-Jarai Z, Meitz J, Hamoudi R, Hope Q, Osin P, Jackson R, Southgate C, Singh R, Falconer A, Dearnaley DP, Ardern-Jones A, Murkin A, Dowe A, Kelly J, Williams S, Oram R, Stevens M, Teare DM, Ponder BA, Gayther SA, Easton DF, Eeles RA, Cancer Research UK/Bristish Prostate Group UK Familial Prostate Cancer Study Collaborators; British Association of Urological Surgeons Section of Oncology (2003) Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. Am J Hum Genet 72(1):1–12

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Kirchhoff T, Kauff ND, Mitra N, Nafa K, Huang H, Palmer C, Gulati T, Wadsworth E, Donat S, Robson ME, Ellis NA, Offit K (2004) BRCA mutations and risk of prostate cancer in Ashkenazi Jews. Clin Cancer Res 10(9):2918–2921

    Article  CAS  PubMed  Google Scholar 

  5. Agalliu I, Kwon EM, Zadory D, McIntosh L, Thompson J, Stanford JL, Ostrander EA (2007) Germline mutations in the BRCA2 gene and susceptibility to hereditary prostate cancer. Clin Cancer Res 13(3):839–843

    Article  CAS  PubMed  Google Scholar 

  6. Fachal L, Gómez-Caamaño A, Celeiro-Muñoz C, Peleteiro P, Blanco A, Carballo A, Forteza J, Carracedo A, Vega A (2011) BRCA1 mutations do not increase prostate cancer risk: results from a meta-analysis including new data. Prostate 71(16):1768–1779. doi:10.1002/pros.21394

    Article  CAS  PubMed  Google Scholar 

  7. Tai YC, Domchek S, Parmigiani G, Chen S (2007) Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 99(23):1811–1814

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Evans DG, Susnerwala I, Dawson J, Woodward E, Maher ER, Lalloo F (2010) Risk of breast cancer in male BRCA2 carriers. J Med Genet 47(10):710–711. doi:10.1136/jmg.2009.075176

    Article  CAS  PubMed  Google Scholar 

  9. Thompson D, Easton DF, Breast Cancer Linkage Consortium (2002) Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst 94(18):1358–1365

    Article  CAS  PubMed  Google Scholar 

  10. Liede A, Karlan BY, Narod SA (2004) Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol 22(4):735–742

    Article  CAS  PubMed  Google Scholar 

  11. Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Fan I, Tang J, Li S, Zhang S, Shaw PA, Narod SA (2006) Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J Natl Cancer Inst 98(23):1694–1706

    Article  CAS  PubMed  Google Scholar 

  12. Abeliovich D, Kaduri L, Lerer I, Weinberg N, Amir G, Sagi M, Zlotogora J, Heching N, Peretz T (1997) The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60 % of ovarian cancer and 30 % of early-onset breast cancer patients among Ashkenazi women. Am J Hum Genet 60(3):505–514

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Laitman Y, Simeonov M, Herskovitz L, Kushnir A, Shimon-Paluch S, Kaufman B, Zidan J, Friedman E (2012) Recurrent germline mutations in BRCA1 and BRCA2 genes in high risk families in Israel. Breast Cancer Res Treat 133(3):1153–1157. doi:10.1007/s10549-012-2006-8

    Article  CAS  PubMed  Google Scholar 

  14. Fishler Y, Barchana M, Keinan-Boker L, Ifrah A. Blau, S. Cancer in Israel. Trends of incidence and mortality, 1982–2002, and update of selected data, 2004. Israel Center for Disease Control, 2008; Publication #310 [Hebrew]

  15. Moran A, O’Hara C, Khan S, Shack L, Woodward E, Maher ER, Lalloo F, Evans DG (2012) Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations. Fam Cancer 11(2):235–242. doi:10.1007/s10689-011-9506-2

    Article  CAS  PubMed  Google Scholar 

  16. Gallagher DJ, Gaudet MM, Pal P, Kirchhoff T, Balistreri L, Vora K, Bhatia J, Stadler Z, Fine SW, Reuter V, Zelefsky M, Morris MJ, Scher HI, Klein RJ, Norton L, Eastham JA, Scardino PT, Robson ME, Offit K (2010) Germline BRCA mutations denote a clinicopathologic subset of prostate cancer. Clin Cancer Res 16(7):2115–2121. doi:10.1158/1078-0432.CCR-09-2871

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Mahon SM (2014) Cancer risks for men with BRCA1/2 mutations. Oncol Nurs Forum 41(1):99–101. doi:10.1188/14.ONF.99-101

    Article  PubMed  Google Scholar 

  18. Mersch J, Jackson MA, Park M, Nebgen D, Peterson SK, Singletary C, Arun BK, Litton JK (2015) Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer 121(2):269–275. doi:10.1002/cncr.29041

    Article  CAS  PubMed  Google Scholar 

  19. Sud A, Wham D, Catalano M, Guda NM (2014) Promising outcomes of screening for pancreatic cancer by genetic testing and endoscopic ultrasound. Pancreas 43(3):458–461. doi:10.1097/MPA.0000000000000052

    Article  CAS  PubMed  Google Scholar 

  20. Lami G, Biagini MR, Galli A (2014) Endoscopic ultrasonography for surveillance of individuals at high risk for pancreatic cancer. World J Gastrointest Endosc 6(7):272–285. doi:10.4253/wjge.v6.i7.272

    Article  PubMed Central  PubMed  Google Scholar 

  21. Canto MI, Harinck F, Hruban RH, Offerhaus GJ, Poley JW, Kamel I, Nio Y, Schulick RS, Bassi C, Kluijt I, Levy MJ, Chak A, Fockens P, Goggins M, Bruno M, International Cancer of Pancreas Screening (CAPS) Consortium (2014) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut 62(3):339–347. doi:10.1136/gutjnl-2012-303108

    Article  Google Scholar 

  22. Lubinski J, Phelan CM, Ghadirian P, Lynch HT, Garber J, Weber B, Tung N, Horsman D, Isaacs C, Monteiro AN, Sun P, Narod SA (2004) Cancer variation associated with the position of the mutation in the BRCA2 gene. Fam Cancer 3(1):1–10

    Article  CAS  PubMed  Google Scholar 

  23. Cybulski C, Górski B, Gronwald J, Huzarski T, Byrski T, Debniak T, Jakubowska A, Wokołorczyk D, Gliniewicz B, Sikorski A, Stawicka M, Godlewski D, Kwias Z, Antczak A, Krajka K, Lauer W, Sosnowski M, Sikorska-Radek P, Bar K, Klijer R, Romuald Z, Małkiewicz B, Borkowski A, Borkowski T, Szwiec M, Posmyk M, Narod SA, Lubiński J (2008) BRCA1 mutations and prostate cancer in Poland. Eur J Cancer Prev 17(1):62–66

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was in part funded by a Grant from the Israeli cancer association through the Israeli consortium for inherited cancer. We wish to acknowledge the assistance of the Meirav Comprehensive breast cancer center team at the Sheba Medical Center for assistance in this study.

Conflict of interest

All authors declare that they have no conflicts of interest.

Ethical Statement

The study was performed after approval by the local IRB (SMC 1492-14) and each participant gave an informed consent.

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Correspondence to Eitan Friedman.

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Laitman, Y., Keinan Boker, L., Liphsitz, I. et al. Cancer risks in Jewish male BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat 150, 631–635 (2015). https://doi.org/10.1007/s10549-015-3340-4

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  • DOI: https://doi.org/10.1007/s10549-015-3340-4

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