Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Germline BRCA mutation in male carriers—ripe for precision oncology?



Prostate cancer (PC) is one of the known heritable cancers with individual variations attributed to genetic factors. BRCA1 and BRCA2 are tumour suppressor genes with crucial roles in repairing DNA and thereby maintaining genomic integrity. Germline BRCA mutations predispose to multiple familial tumour types including PC.


We performed a Pubmed database search along with review of reference lists from prominent articles to capture papers exploring the association between BRCA mtuations and prostate cancer risk and prognosis. Articles were retrieved until May 2017 and filtered for relevance, and publication type.


We explored familial PC genetics; discussed the discovery and magnitude of the association between BRCA mutations and PC risk and outcome; examined implications of factoring BRCA mutations into PC screening; and discussed the rationale for chemoprevention in this high-risk population. We confirmed that BRCA1/2 mutations confer an up to 4.5-fold and 8.3-fold increased risk of PC, respectively. BRCA2 mutations are associated with an increased risk of high-grade disease, progression to metastatic castration-resistant disease, and 5-year cancer-specific survival rates of 50 to 60%.


Despite the growing body of research on DNA repair genes, deeper analysis is needed to understand the aetiological role of germline BRCA mutations in the natural history of PC. There is a need for awareness to screen for this marker of PC risk. There is similarly an opportunity for structured PC screening programs for BRCA mutation carriers. Finally, further research is required to identify potential chemopreventive strategies for this high-risk subgroup.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    Helgesen F, Holmberg L, Johansson JE, Bergstrom R, Adami HO. Trends in prostate cancer survival in Sweden, 1960 through 1988: evidence of increasing diagnosis of nonlethal tumors. J. Natl Cancer Inst.1996;88:1216–21.

    CAS  PubMed  Google Scholar 

  2. 2.

    Bratt O, Drevin L, Akre O, Garmo H, Stattin P. Family history and probability of prostate cancer, differentiated by risk category: a nationwide population-based study. J Natl Cancer Inst. 2016;108. pii: djw110.

    PubMed  Google Scholar 

  3. 3.

    Sundararajan S, Ahmed A, Goodman OB Jr. The relevance of BRCA genetics to prostate cancer pathogenesis and treatment. Clin Adv Hematol Oncol. 2011;9:748–55.

    PubMed  Google Scholar 

  4. 4.

    Mersch J, Jackson MA, Park M, Nebgen D, Peterson SK, Singletary C, et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer. 2015;121:269–75.

    CAS  PubMed  Google Scholar 

  5. 5.

    Castro E, Eeles R. The role of BRCA1 and BRCA2 in prostate cancer. Asian J Androl. 2012;14:409–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Castro E, Goh C, Leongamornlert D, Saunders E, Tymrakiewicz M, Dadaev T, et al. Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer. Eur Urol. 2015;68:186–93.

    CAS  PubMed  Google Scholar 

  7. 7.

    Carter BS, Beaty TH, Steinberg GD, Childs B, Walsh PC. Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci USA. 1992;89:3367–71.

    CAS  PubMed  Google Scholar 

  8. 8.

    Hemminki K. Familial risk and familial survival in prostate cancer. World J Urol. 2012;30:143–8.

    PubMed  Google Scholar 

  9. 9.

    Potter SR, Partin AW. Hereditary and familial prostate cancer: biologic aggressiveness and recurrence. Rev Urol. 2000;2:35–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Rokman A, Ikonen T, Seppala EH, Nupponen N, Autio V, Mononen N, et al. Germline alterations of the RNASEL gene, a candidate HPC1 gene at 1q25, in patients and families with prostate cancer. Am J Hum Genet. 2002;70:1299–304.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Tavtigian SV, Simard J, Teng DH, Abtin V, Baumgard M, Beck A, et al. A candidate prostate cancer susceptibility gene at chromosome 17p. Nat Genet. 2001;27:172–80.

    CAS  PubMed  Google Scholar 

  12. 12.

    Xu J, Zheng SL, Komiya A, Mychaleckyj JC, Isaacs SD, Hu JJ, et al. Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. Nat Genet. 2002;32:321–5.

    CAS  PubMed  Google Scholar 

  13. 13.

    Brodie A, Azaria JR, Ofran Y. How far from the SNP may the causative genes be? Nucleic Acids Res. 2016;44:6046–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Nakagawa H, Akamatsu S, Takata R, Takahashi A, Kubo M, Nakamura Y. Prostate cancer genomics, biology, and risk assessment through genome-wide association studies. Cancer Sci. 2012;103:607–13.

    CAS  PubMed  Google Scholar 

  15. 15.

    Castro E, Goh C, Olmos D, Saunders E, Leongamornlert D, Tymrakiewicz M, et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J Clin Oncol: Off J Am Soc Clin Oncol. 2013;31:1748–57.

    CAS  Google Scholar 

  16. 16.

    Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994;266:66–71.

    CAS  PubMed  Google Scholar 

  17. 17.

    Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science. 1994;265:2088–90.

    CAS  PubMed  Google Scholar 

  18. 18.

    Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378:789–92.

    CAS  PubMed  Google Scholar 

  19. 19.

    Gudmundsdottir K, Ashworth A. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene. 2006;25:5864–74.

    CAS  PubMed  Google Scholar 

  20. 20.

    Edwards SM, Kote-Jarai Z, Meitz J, Hamoudi R, Hope Q, Osin P, et al. Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. Am J Hum Genet 2003;72:1–12.

    CAS  PubMed  Google Scholar 

  21. 21.

    Venkitaraman AR. Functions of BRCA1 and BRCA2 in the biological response to DNA damage. J Cell Sci. 2001;114:3591–8.

    CAS  PubMed  Google Scholar 

  22. 22.

    Cavanagh H, Rogers KM. The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers. Hereditary Cancer Clin Pract. 2015;13:16.

    Google Scholar 

  23. 23.

    Deng CX. BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution. Nucleic Acids Res. 2006;34:1416–1426.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015;373:1697–708.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Schlacher K, Christ N, Siaud N, Egashira A, Wu H, Jasin M. Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11. Cell. 2011;145:529–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer. 2011;12:68–78.

    PubMed  PubMed Central  Google Scholar 

  27. 27.

    Breast Cancer Linkage C. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst. 1999;91:1310–6.

    Google Scholar 

  28. 28.

    Moslehi R, Chu W, Karlan B, Fishman D, Risch H, Fields A, et al. BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. Am J Hum Genet. 2000;66:1259–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Fan I, et al. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J Natl Cancer Inst. 2006;98:1694–706.

    CAS  PubMed  Google Scholar 

  30. 30.

    Moran A, O’Hara C, Khan S, Shack L, Woodward E, Maher ER, et al. Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations. Fam Cancer. 2012;11:235–42.

    CAS  PubMed  Google Scholar 

  31. 31.

    Easton DF, Steele L, Fields P, Ormiston W, Averill D, Daly PA, et al. Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12-13. Am J Hum Genet. 1997;61:120–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Anderson DE, Badzioch MD. Breast cancer risks in relatives of male breast cancer patients. J Natl Cancer Inst. 1992;84:1114–7.

    CAS  PubMed  Google Scholar 

  33. 33.

    Liede A, Karlan BY, Narod SA. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol: Off J Am Soc Clin Oncol. 2004;22:735–42.

    CAS  Google Scholar 

  34. 34.

    Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994;343:692–5.

    CAS  PubMed  Google Scholar 

  35. 35.

    Sigurdsson S, Thorlacius S, Tomasson J, Tryggvadottir L, Benediktsdottir K, Eyfjord JE, et al. BRCA2 mutation in Icelandic prostate cancer patients. J Mol Med. 1997;75:758–61.

    CAS  PubMed  Google Scholar 

  36. 36.

    Mitra AV, Bancroft EK, Barbachano Y, Page EC, Foster CS, Jameson C, et al. Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study. BJU Int. 2011;107:28–39.

    PubMed  Google Scholar 

  37. 37.

    Bancroft EK, Page EC, Castro E, Lilja H, Vickers A, Sjoberg D, et al. Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: results from the initial screening round of the IMPACT study. Eur Urol 2014;66:489–99.

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Malone KE, Daling JR, Doody DR, Hsu L, Bernstein L, Coates RJ, et al. Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years. Cancer Res 2006;66:8297–308.

    CAS  PubMed  Google Scholar 

  39. 39.

    Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol: Off J Am Soc Clin Oncol. 2007;25:1329–33.

    Google Scholar 

  40. 40.

    Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med. 1997;336:1401–8.

    CAS  PubMed  Google Scholar 

  41. 41.

    Hubert A, Peretz T, Manor O, Kaduri L, Wienberg N, Lerer I, et al. The Jewish Ashkenazi founder mutations in the BRCA1/BRCA2 genes are not found at an increased frequency in Ashkenazi patients with prostate cancer. Am J Hum Genet. 1999;65:921–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Lehrer S, Fodor F, Stock RG, Stone NN, Eng C, Song HK, et al. Absence of 185delAG mutation of the BRCA1 gene and 6174delT mutation of the BRCA2 gene in Ashkenazi Jewish men with prostate cancer. Br J Cancer. 1998;78:771–3.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Nastiuk KL, Mansukhani M, Terry MB, Kularatne P, Rubin MA, Melamed J, et al. Common mutations in BRCA1 and BRCA2 do not contribute to early prostate cancer in Jewish men. Prostate. 1999;40:172–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Hamel N, Kotar K, Foulkes WD. Founder mutations in BRCA1/2 are not frequent in Canadian Ashkenazi Jewish men with prostate cancer. BMC Med Genet. 2003;4:7.

    PubMed  PubMed Central  Google Scholar 

  45. 45.

    Vazina A, Baniel J, Yaacobi Y, Shtriker A, Engelstein D, Leibovitz I, et al. The rate of the founder Jewish mutations in BRCA1 and BRCA2 in prostate cancer patients in Israel. Br J Cancer. 2000;83:463–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Roa BB, Boyd AA, Volcik K, Richards CS. Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet. 1996;14:185–7.

    CAS  PubMed  Google Scholar 

  47. 47.

    Kirchhoff T, Kauff ND, Mitra N, Nafa K, Huang H, Palmer C, et al. BRCA mutations and risk of prostate cancer in Ashkenazi Jews. Clin Cancer Res: Off J Am Assoc Cancer Res. 2004;10:2918–21.

    CAS  Google Scholar 

  48. 48.

    Thompson D, Easton DF. Breast Cancer Linkage C. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002;94:1358–65.

    CAS  PubMed  Google Scholar 

  49. 49.

    Leongamornlert D, Mahmud N, Tymrakiewicz M, Saunders E, Dadaev T, Castro E, et al. Germline BRCA1 mutations increase prostate cancer risk. Br J Cancer. 2012;106:1697–01.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Kote-Jarai Z, Leongamornlert D, Saunders E, Tymrakiewicz M, Castro E, Mahmud N, et al. BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients. Br J Cancer. 2011;105:1230–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    van Asperen CJ, Brohet RM, Meijers-Heijboer EJ, Hoogerbrugge N, Verhoef S, Vasen HF, et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet 2005;42:711–9.

    PubMed  PubMed Central  Google Scholar 

  52. 52.

    Giusti RM, Rutter JL, Duray PH, Freedman LS, Konichezky M, Fisher-Fischbein J, et al. A twofold increase in BRCA mutation related prostate cancer among Ashkenazi Israelis is not associated with distinctive histopathology. J Med Genet. 2003;40:787–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Gallagher DJ, Gaudet MM, Pal P, Kirchhoff T, Balistreri L, Vora K, et al. Germline BRCA mutations denote a clinicopathologic subset of prostate cancer. Clin Cancer Res: Off J Am Assoc Cancer Res. 2010;16:2115–21.

    CAS  Google Scholar 

  54. 54.

    Agalliu I, Gern R, Leanza S, Burk RD. Associations of high-grade prostate cancer with BRCA1 and BRCA2 founder mutations. Clin Cancer Res: Off J Am Assoc Cancer Res. 2009;15:1112–20.

    CAS  Google Scholar 

  55. 55.

    Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016;375:443–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Tryggvadottir L, Vidarsdottir L, Thorgeirsson T, Jonasson JG, Olafsdottir EJ, Olafsdottir GH, et al. Prostate cancer progression and survival in BRCA2 mutation carriers. J Natl Cancer Inst 2007;99:929–35.

    CAS  PubMed  Google Scholar 

  57. 57.

    Narod SA, Neuhausen S, Vichodez G, Armel S, Lynch HT, Ghadirian P, et al. Rapid progression of prostate cancer in men with a BRCA2 mutation. Br J Cancer 2008;99:371–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Na R, Zheng SL, Han M, Yu H, Jiang D, Shah S, et al. Germline mutations in ATM and BRCA1/2 distinguish risk for lethal and indolent prostate cancer and are associated with early age at death. Eur Urol. 2017;71:740–7.

    CAS  PubMed  Google Scholar 

  59. 59.

    Akbari MR, Wallis CJ, Toi A, Trachtenberg J, Sun P, Narod SA, et al. The impact of a BRCA2 mutation on mortality from screen-detected prostate cancer. Br J Cancer 2014;111:1238–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Walker R, Louis A, Berlin A, Horsburgh S, Bristow RG, Trachtenberg J. Prostate cancer screening characteristics in men with BRCA1/2 mutations attending a high-risk prevention clinic. Can Urol Assoc J. 2014;8:E783–8.

    PubMed  PubMed Central  Google Scholar 

  61. 61.

    Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;161:1215–28.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS, et al. Integrative genomic profiling of human prostate cancer. Cancer Cell. 2010;18:11–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Cancer Genome Atlas Research N. The molecular taxonomy of primary prostate cancer. Cell. 2015;163:1011–25.

    Google Scholar 

  64. 64.

    Taylor RA, Fraser M, Livingstone J, Espiritu SM, Thorne H, Huang V, et al. Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories. Nat Commun. 2017;8:13671.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Cui M, Gao XS, Gu X, Guo W, Li X, Ma M et al. BRCA2 mutations should be screened early and routinely as markers of poor prognosis: evidence from 8,988 patients with prostate cancer. Oncotarget. 2017;8:40222–232.

  66. 66.

    Agalliu I, Karlins E, Kwon EM, Iwasaki LM, Diamond A, Ostrander EA, et al. Rare germline mutations in the BRCA2 gene are associated with early-onset prostate cancer. Br J Cancer. 2007;97:826–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Andriole GL, Crawford ED, Grubb RL 3rd, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360:1310–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    McGregor M, Hanley JA, Boivin JF, McLean RG. Screening for prostate cancer: estimating the magnitude of overdetection. Can Med Assoc J. 1998;159:1368–72.

    CAS  Google Scholar 

  69. 69.

    Force USPST. Draft Recommendation Statement: Prostate Cancer: Screening. U.S. Preventive Services Task Force. 2017.

  70. 70.

    Carroll PR, Parsons JK, Andriole G, Bahnson RR, Castle EP, Catalona WJ, et al. NCCN guidelines insights: prostate cancer early detection, Version 2.2016. J Natl Compr Cancer Netw. 2016;14:509–519.

    Google Scholar 

  71. 71.

    Manchanda R, Legood R, Burnell M, McGuire A, Raikou M, Loggenberg K, et al. Cost-effectiveness of population screening for BRCA mutations in Ashkenazi jewish women compared with family history-based testing. J Natl Cancer Inst. 2015;107:380.

    PubMed  Google Scholar 

  72. 72.

    Grann VR, Whang W, Jacobson JS, Heitjan DF, Antman KH, Neugut AI. Benefits and costs of screening Ashkenazi Jewish women for BRCA1 and BRCA2. J Clin Oncol: Off J Am Soc Clin Oncol. 1999;17:494–500.

    CAS  Google Scholar 

  73. 73.

    Moyer VA, Force USPST. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160:271–81.

    PubMed  Google Scholar 

  74. 74.

    Prorok PC, Andriole GL, Bresalier RS, Buys SS, Chia D, Crawford ED, et al. Design of the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Control Clin Trials. 2000;21:S273–S309.

    Google Scholar 

  75. 75.

    Walsh PC. The search for the missing heritability of prostate cancer. Eur Urol. 2017;72:657–659.

    PubMed  Google Scholar 

  76. 76.

    Kim DH, Crawford B, Ziegler J, Beattie MS. Prevalence and characteristics of pancreatic cancer in families with BRCA1 and BRCA2 mutations. Fam Cancer. 2009;8:153–8.

    CAS  PubMed  Google Scholar 

  77. 77.

    Liede A, Metcalfe K, Hanna D, Hoodfar E, Snyder C, Durham C, et al. Evaluation of the needs of male carriers of mutations in BRCA1 or BRCA2 who have undergone genetic counseling. Am J Hum Genet 2000;67:1494–04.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Mitri ZI, Jackson M, Garby C, Song J, Giordano SH, Hortobagyi GN, et al. BRCAPRO 6.0 model validation in male patients presenting for BRCA testing. Oncologist. 2015;20:593–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Berry DA, Iversen ES Jr., Gudbjartsson DF, Hiller EH, Garber JE, Peshkin BN, et al. BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes. J Clin Oncol: Off J Am Soc Clin Oncol. 2002;20:2701–12.

    CAS  Google Scholar 

  80. 80.

    Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009;301:39–51.

    CAS  PubMed  Google Scholar 

  81. 81.

    Ma J, Stampfer MJ, Gann PH, Hough HL, Giovannucci E, Kelsey KT, et al. Vitamin D receptor polymorphisms, circulating vitamin D metabolites, and risk of prostate cancer in United States physicians. Cancer Epidemiol Biomarkers Prev: Publ Am Assoc Cancer Res Am Soc Prev Oncol. 1998;7:385–90.

    CAS  Google Scholar 

  82. 82.

    Raghow S, Hooshdaran MZ, Katiyar S, Steiner MS. Toremifene prevents prostate cancer in the transgenic adenocarcinoma of mouse prostate model. Cancer Res. 2002;62:1370–6.

    CAS  PubMed  Google Scholar 

  83. 83.

    Mahmud SM, Franco EL, Turner D, Platt RW, Beck P, Skarsgard D, et al. Use of non-steroidal anti-inflammatory drugs and prostate cancer risk: a population-based nested case-control study. PLoS ONE. 2011;6:e16412.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362:1192–02.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Unger JM, Till C, Thompson IM, Jr., Tangen CM, Goodman PJ, Wright JD et al. Long-term consequences of finasteride vs placebo in the prostate cancer prevention trial. J Natl Cancer Inst. 2016;108. pii: djw168.

    PubMed  PubMed Central  Google Scholar 

  86. 86.

    Foundation P-FS. Post-Finasteride Syndrome Foundation 2017.

  87. 87.

    Hamilton RJ, Kahwati LC, Kinsinger LS. Knowledge and use of finasteride for the prevention of prostate cancer. Cancer Epidemiol Biomarkers Prev: Publ Am Assoc Cancer Res Am Soc Prev Oncol. 2010;19:2164–71.

    CAS  Google Scholar 

  88. 88.

    Zeliadt SB, Ramsey SD. Cost-effectiveness of prostate cancer chemoprevention among high-risk men. Exp Rev Pharmacoecon Outcomes Res. 2010;10:505–8.

    Google Scholar 

  89. 89.

    Reed SD, Scales CD Jr., Stewart SB, Sun J, Moul JW, Schulman KA, et al. Effects of family history and genetic polymorphism on the cost-effectiveness of chemoprevention with finasteride for prostate cancer. J Urol. 2011;185:841–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Kattan MW, Earnshaw SR, McDade CL, Black LK, Andriole GL. Cost effectiveness of chemoprevention for prostate cancer with dutasteride in a high-risk population based on results from the REDUCE clinical trial. Appl Health Econ Health Policy. 2011;9:305–15.

    PubMed  Google Scholar 

  91. 91.

    Hamilton RJ, Goldberg KC, Platz EA, Freedland SJ. The influence of statin medications on prostate-specific antigen levels. J Natl Cancer Inst. 2008;100:1511–8.

    CAS  PubMed  Google Scholar 

  92. 92.

    Hamilton RJ, Banez LL, Aronson WJ, Terris MK, Platz EA, Kane CJ, et al. Statin medication use and the risk of biochemical recurrence after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. Cancer. 2010;116:3389–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93.

    Hager MH, Solomon KR, Freeman MR. The role of cholesterol in prostate cancer. Curr Opin Clin Nutr Metab Care. 2006;9:379–85.

    CAS  PubMed  Google Scholar 

  94. 94.

    Zhuang L, Kim J, Adam RM, Solomon KR, Freeman MR. Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. J Clin Invest. 2005;115:959–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 95.

    Friedman GD, Flick ED, Udaltsova N, Chan J, Quesenberry CP Jr., Habel LA. Screening statins for possible carcinogenic risk: up to 9 years of follow-up of 361,859 recipients. Pharmacoepidemiol Drug Saf. 2008;17:27–36.

    PubMed  Google Scholar 

  96. 96.

    Morote J, Celma A, Planas J, Placer J, de Torres I, Olivan M, et al. Role of serum cholesterol and statin use in the risk of prostate cancer detection and tumor aggressiveness. Int J Mol Sci. 2014;15:13615–23.

    PubMed  PubMed Central  Google Scholar 

  97. 97.

    Joshua AM, Zannella VE, Downes MR, Bowes B, Hersey K, Koritzinsky M, et al. A pilot ‘window of opportunity’ neoadjuvant study of metformin in localised prostate cancer. Prostate Cancer Prostatic Dis. 2014;17:252–8.

    CAS  PubMed  Google Scholar 

  98. 98.

    Tseng CH. Metformin significantly reduces incident prostate cancer risk in Taiwanese men with type 2 diabetes mellitus. Eur J Cancer. 2014;50:2831–7.

    CAS  PubMed  Google Scholar 

  99. 99.

    Deng D, Yang Y, Tang X, Skrip L, Qiu J, Wang Y, et al. Association between metformin therapy and incidence, recurrence and mortality of prostate cancer: evidence from a meta-analysis. Diabetes Metab Res Rev. 2015;31:595–602.

    CAS  PubMed  Google Scholar 

  100. 100.

    Lehman DM, Lorenzo C, Hernandez J, Wang CP. Statin use as a moderator of metformin effect on risk for prostate cancer among type 2 diabetic patients. Diab Care. 2012;35:1002–7.

    CAS  Google Scholar 

  101. 101.

    Cossack M, Ghaffary C, Watson P, Snyder C, Lynch H. Aspirin use is associated with lower prostate cancer risk in male carriers of BRCA mutations. J Genet Couns. 2014;23:187–91.

    PubMed  Google Scholar 

  102. 102.

    Shebl FM, Sakoda LC, Black A, Koshiol J, Andriole GL, Grubb R, et al. Aspirin but not ibuprofen use is associated with reduced risk of prostate cancer: a PLCO study. Br J Cancer. 2012;107:207–214.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. 103.

    Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem. 2000;69:145–82.

    CAS  PubMed  Google Scholar 

  104. 104.

    McGlynn P, Lloyd RG. Recombinational repair and restart of damaged replication forks. Nat Rev Mol Cell Biol. 2002;3:859–70.

    CAS  PubMed  Google Scholar 

  105. 105.

    To C, Kim EH, Royce DB, Williams CR, Collins RM, Risingsong R, et al. The PARP inhibitors, veliparib and olaparib, are effective chemopreventive agents for delaying mammary tumor development in BRCA1-deficient mice. Cancer Prev. Res. 2014;7:698–707.

    CAS  Google Scholar 

  106. 106.

    Sandhu SK, Omlin A, Hylands L, Miranda S, Barber LJ, Riisnaes R, et al. Poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of advanced germline BRCA2 mutant prostate cancer. Ann Oncol: Off J Eur Soc Med Oncol. 2013;24:1416–8.

    CAS  Google Scholar 

  107. 107.

    Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–34.

    CAS  PubMed  Google Scholar 

Download references


RL is supported by the Foundation for Science and Technology, Government of Portugal, SFRH/BD/102232/2014 Individual Doctoral Grant.

Author information



Corresponding author

Correspondence to Robert James Hamilton.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Leão, R.R.N., Price, A.J. & James Hamilton, R. Germline BRCA mutation in male carriers—ripe for precision oncology?. Prostate Cancer Prostatic Dis 21, 48–56 (2018).

Download citation

Further reading


Quick links