Skip to content
    Font Size

    Genetics of Prostate Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Introduction

    Table 1. Relative Risk (RR) Related to Family History of Prostate Cancera continued...

    Risk of Other Cancers in Multiple-Case Families

    Several reports have suggested an elevated risk of various other cancers among relatives within multiple-case prostate cancer families, but none of these associations have been established definitively.[55,56,57]

    In a population-based Finnish study of 202 multiple-case prostate cancer families, no excess risk of all cancers combined (other than prostate cancer) was detected in 5,523 family members. Female family members had a marginal excess of gastric cancer (standardized incidence ratio [SIR], 1.9; 95% CI, 1.0-3.2). No difference in familial cancer risk was observed when families affected by clinically aggressive prostate cancers were compared with those having nonaggressive prostate cancer. These data suggest that familial prostate cancer is a cancer site-specific disorder.[58]

    Inheritance of Prostate Cancer Risk

    Many types of epidemiologic studies (case-control, cohort, twin, family) strongly suggest that prostate cancer susceptibility genes exist in the population. An analysis of monozygotic and dizygotic twin pairs in Scandinavia concluded that 42% (95% CI, 29-50) of prostate cancer risk may be accounted for by heritable factors.[59] This is in agreement with a previous U.S. study that showed a concordance of 7.1% between dizygotic twin pairs and a 27% concordance between monozygotic twin pairs.[60] The first segregation analysis was performed in 1992 using families from 740 consecutive probands who had radical prostatectomies between 1982 and 1989. The study results suggested that familial clustering of disease among men with early-onset prostate cancer was best explained by the presence of a rare (frequency of 0.003) autosomal dominant, highly penetrant allele(s).[12] Hereditary prostate cancer susceptibility genes were predicted to account for almost half of early-onset disease (age 55 years or younger). In addition, early-onset disease has been further supported to have a strong genetic component from the study of common variants associated with disease onset before age 55 years.[61]

    Subsequent segregation analyses generally agreed with the conclusions but differed in the details regarding frequency, penetrance, and mode of inheritance.[62,63,64] A study of 4,288 men who underwent radical prostatectomy between 1966 and 1995 found that the best fitting genetic model of inheritance was the presence of a rare, autosomal dominant susceptibility gene (frequency of 0.06). In this study, the lifetime risk in carriers was estimated to be 89% by age 85 years and 3.9% for noncarriers.[60] This study also suggested the presence of genetic heterogeneity, as the model did not reliably predict prostate cancer risk in FDRs of probands who were diagnosed at age 70 years or older. More recent segregation analyses have concluded that there are multiple genes associated with prostate cancer [65,66,67,68] in a pattern similar to other adult-onset hereditary cancer syndromes, such as those involving the breast, ovary, colorectum, kidney, and melanoma. In addition, a segregation analysis of 1,546 families from Finland found evidence for Mendelian recessive inheritance. Results showed that individuals carrying the risk allele were diagnosed with prostate cancer at younger ages (<66 years) than noncarriers. This is the first segregation analysis to show a recessive mode of inheritance.[69]


    1. American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed May 21, 2014.
    2. Ruijter E, van de Kaa C, Miller G, et al.: Molecular genetics and epidemiology of prostate carcinoma. Endocr Rev 20 (1): 22-45, 1999.
    3. Stanford JL, Stephenson RA, Coyle LM, et al., eds.: Prostate Cancer Trends 1973-1995. Bethesda, Md: National Cancer Institute, 1999. NIH Pub. No. 99-4543. Also available online. Last accessed June 18, 2014.
    4. Miller BA, Kolonel LN, Bernstein L, et al., eds.: Racial/Ethnic Patterns of Cancer in the United States 1988-1992. Bethesda, Md: National Cancer Institute, 1996. NIH Pub. No. 96-4104. Also available online. Last accessed June 18, 2014.
    5. Haas GP, Sakr WA: Epidemiology of prostate cancer. CA Cancer J Clin 47 (5): 273-87, 1997 Sep-Oct.
    6. Hemminki K, Rawal R, Bermejo JL: Prostate cancer screening, changing age-specific incidence trends and implications on familial risk. Int J Cancer 113 (2): 312-5, 2005.
    7. Witte JS: Prostate cancer genomics: towards a new understanding. Nat Rev Genet 10 (2): 77-82, 2009.
    8. Altekruse SF, Kosary CL, Krapcho M, et al.: SEER Cancer Statistics Review, 1975-2007. Bethesda, Md: National Cancer Institute, 2010. Also available online. Last accessed October 3, 2014.
    9. Bunker CH, Patrick AL, Konety BR, et al.: High prevalence of screening-detected prostate cancer among Afro-Caribbeans: the Tobago Prostate Cancer Survey. Cancer Epidemiol Biomarkers Prev 11 (8): 726-9, 2002.
    10. Optenberg SA, Thompson IM, Friedrichs P, et al.: Race, treatment, and long-term survival from prostate cancer in an equal-access medical care delivery system. JAMA 274 (20): 1599-605, 1995 Nov 22-29.
    11. Steinberg GD, Carter BS, Beaty TH, et al.: Family history and the risk of prostate cancer. Prostate 17 (4): 337-47, 1990.
    12. Carter BS, Beaty TH, Steinberg GD, et al.: Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci U S A 89 (8): 3367-71, 1992.
    13. Ghadirian P, Howe GR, Hislop TG, et al.: Family history of prostate cancer: a multi-center case-control study in Canada. Int J Cancer 70 (6): 679-81, 1997.
    14. Stanford JL, Ostrander EA: Familial prostate cancer. Epidemiol Rev 23 (1): 19-23, 2001.
    15. Matikaine MP, Pukkala E, Schleutker J, et al.: Relatives of prostate cancer patients have an increased risk of prostate and stomach cancers: a population-based, cancer registry study in Finland. Cancer Causes Control 12 (3): 223-30, 2001.
    16. Grönberg H, Damber L, Damber JE: Familial prostate cancer in Sweden. A nationwide register cohort study. Cancer 77 (1): 138-43, 1996.
    17. Cannon L, Bishop DT, Skolnick M, et al.: Genetic epidemiology of prostate cancer in the Utah Mormon genealogy. Cancer Surv 1 (1): 47-69, 1982.
    18. Bratt O, Garmo H, Adolfsson J, et al.: Effects of prostate-specific antigen testing on familial prostate cancer risk estimates. J Natl Cancer Inst 102 (17): 1336-43, 2010.
    19. Kalish LA, McDougal WS, McKinlay JB: Family history and the risk of prostate cancer. Urology 56 (5): 803-6, 2000.
    20. Cerhan JR, Parker AS, Putnam SD, et al.: Family history and prostate cancer risk in a population-based cohort of Iowa men. Cancer Epidemiol Biomarkers Prev 8 (1): 53-60, 1999.
    21. Kiciński M, Vangronsveld J, Nawrot TS: An epidemiological reappraisal of the familial aggregation of prostate cancer: a meta-analysis. PLoS One 6 (10): e27130, 2011.
    22. Brandt A, Bermejo JL, Sundquist J, et al.: Age-specific risk of incident prostate cancer and risk of death from prostate cancer defined by the number of affected family members. Eur Urol 58 (2): 275-80, 2010.
    23. Grönberg H, Wiklund F, Damber JE: Age specific risks of familial prostate carcinoma: a basis for screening recommendations in high risk populations. Cancer 86 (3): 477-83, 1999.
    24. Damber L, Grönberg H, Damber JE: Familial prostate cancer and possible associated malignancies: nation-wide register cohort study in Sweden. Int J Cancer 78 (3): 293-7, 1998.
    25. Sellers TA, Potter JD, Rich SS, et al.: Familial clustering of breast and prostate cancers and risk of postmenopausal breast cancer. J Natl Cancer Inst 86 (24): 1860-5, 1994.
    26. Agalliu I, Karlins E, Kwon EM, et al.: Rare germline mutations in the BRCA2 gene are associated with early-onset prostate cancer. Br J Cancer 97 (6): 826-31, 2007.
    27. Edwards SM, Kote-Jarai Z, Meitz J, et al.: Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. Am J Hum Genet 72 (1): 1-12, 2003.
    28. Ford D, Easton DF, Bishop DT, et al.: Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 343 (8899): 692-5, 1994.
    29. Gayther SA, de Foy KA, Harrington P, et al.: The frequency of germ-line mutations in the breast cancer predisposition genes BRCA1 and BRCA2 in familial prostate cancer. The Cancer Research Campaign/British Prostate Group United Kingdom Familial Prostate Cancer Study Collaborators. Cancer Res 60 (16): 4513-8, 2000.
    30. Whittemore AS, Wu AH, Kolonel LN, et al.: Family history and prostate cancer risk in black, white, and Asian men in the United States and Canada. Am J Epidemiol 141 (8): 732-40, 1995.
    31. Carter BS, Bova GS, Beaty TH, et al.: Hereditary prostate cancer: epidemiologic and clinical features. J Urol 150 (3): 797-802, 1993.
    32. Spitz MR, Currier RD, Fueger JJ, et al.: Familial patterns of prostate cancer: a case-control analysis. J Urol 146 (5): 1305-7, 1991.
    33. Goldgar DE, Easton DF, Cannon-Albright LA, et al.: Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst 86 (21): 1600-8, 1994.
    34. Braun MM, Caporaso NE, Page WF, et al.: A cohort study of twins and cancer. Cancer Epidemiol Biomarkers Prev 4 (5): 469-73, 1995 Jul-Aug.
    35. Morganti G, Gianferrari L, Cresseri A, et al.: [Clinico-statistical and genetic research on neoplasms of the prostate]. Acta Genet Stat Med 6 (2): 304-5, 1956.
    36. Woolf CM: An investigation of the familial aspects of carcinoma of the prostate. Cancer 13 (4): 739-744, 1960.
    37. Wu CP, Gu FL: The prostate in eunuchs. Prog Clin Biol Res 370: 249-55, 1991.
    38. Ross RK, Pike MC, Coetzee GA, et al.: Androgen metabolism and prostate cancer: establishing a model of genetic susceptibility. Cancer Res 58 (20): 4497-504, 1998.
    39. Rajender S, Singh L, Thangaraj K: Phenotypic heterogeneity of mutations in androgen receptor gene. Asian J Androl 9 (2): 147-79, 2007.
    40. Gu M, Dong X, Zhang X, et al.: The CAG repeat polymorphism of androgen receptor gene and prostate cancer: a meta-analysis. Mol Biol Rep 39 (3): 2615-24, 2012.
    41. Kolonel LN: Fat, meat, and prostate cancer. Epidemiol Rev 23 (1): 72-81, 2001.
    42. Giovannucci E, Rimm EB, Liu Y, et al.: A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst 94 (5): 391-8, 2002.
    43. Chan JM, Giovannucci EL: Vegetables, fruits, associated micronutrients, and risk of prostate cancer. Epidemiol Rev 23 (1): 82-6, 2001.
    44. Chan JM, Giovannucci EL: Dairy products, calcium, and vitamin D and risk of prostate cancer. Epidemiol Rev 23 (1): 87-92, 2001.
    45. Barnes S: Role of phytochemicals in prevention and treatment of prostate cancer. Epidemiol Rev 23 (1): 102-5, 2001.
    46. Hickey K, Do KA, Green A: Smoking and prostate cancer. Epidemiol Rev 23 (1): 115-25, 2001.
    47. Bernal-Delgado E, Latour-Pérez J, Pradas-Arnal F, et al.: The association between vasectomy and prostate cancer: a systematic review of the literature. Fertil Steril 70 (2): 191-200, 1998.
    48. Stanford JL, Wicklund KG, McKnight B, et al.: Vasectomy and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 8 (10): 881-6, 1999.
    49. Gong Z, Agalliu I, Lin DW, et al.: Obesity is associated with increased risks of prostate cancer metastasis and death after initial cancer diagnosis in middle-aged men. Cancer 109 (6): 1192-202, 2007.
    50. Kristal AR, Gong Z: Obesity and prostate cancer mortality. Future Oncol 3 (5): 557-67, 2007.
    51. Lippman SM, Klein EA, Goodman PJ, 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 301 (1): 39-51, 2009.
    52. Klein EA, Thompson IM Jr, Tangen CM, et al.: Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 306 (14): 1549-56, 2011.
    53. McMaster ML, Feuer EJ, Tucker MA: New malignancies following cancer of the male genital tract. In: Curtis RE, Freedman DM, Ron E, et al., eds.: New Malignancies Among Cancer Survivors: SEER Cancer Registries, 1973-2000. Bethesda, Md: National Cancer Institute, 2006. NIH Pub. No. 05-5302, pp 257-84.
    54. Zhang H, Bermejo JL, Sundquist J, et al.: Prostate cancer as a first and second cancer: effect of family history. Br J Cancer 101 (6): 935-9, 2009.
    55. Isaacs SD, Kiemeney LA, Baffoe-Bonnie A, et al.: Risk of cancer in relatives of prostate cancer probands. J Natl Cancer Inst 87 (13): 991-6, 1995.
    56. Albright LA, Schwab A, Camp NJ, et al.: Population-based risk assessment for other cancers in relatives of hereditary prostate cancer (HPC) cases. Prostate 64 (4): 347-55, 2005.
    57. Grönberg H, Bergh A, Damber JE, et al.: Cancer risk in families with hereditary prostate carcinoma. Cancer 89 (6): 1315-21, 2000.
    58. Pakkanen S, Pukkala E, Kainulainen H, et al.: Incidence of cancer in finnish families with clinically aggressive and nonaggressive prostate cancer. Cancer Epidemiol Biomarkers Prev 18 (11): 3049-56, 2009.
    59. Lichtenstein P, Holm NV, Verkasalo PK, et al.: Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343 (2): 78-85, 2000.
    60. Page WF, Braun MM, Partin AW, et al.: Heredity and prostate cancer: a study of World War II veteran twins. Prostate 33 (4): 240-5, 1997.
    61. Lange EM, Salinas CA, Zuhlke KA, et al.: Early onset prostate cancer has a significant genetic component. Prostate 72 (2): 147-56, 2012.
    62. Schaid DJ, McDonnell SK, Blute ML, et al.: Evidence for autosomal dominant inheritance of prostate cancer. Am J Hum Genet 62 (6): 1425-38, 1998.
    63. Grönberg H, Damber L, Damber JE, et al.: Segregation analysis of prostate cancer in Sweden: support for dominant inheritance. Am J Epidemiol 146 (7): 552-7, 1997.
    64. Verhage BA, Baffoe-Bonnie AB, Baglietto L, et al.: Autosomal dominant inheritance of prostate cancer: a confirmatory study. Urology 57 (1): 97-101, 2001.
    65. Gong G, Oakley-Girvan I, Wu AH, et al.: Segregation analysis of prostate cancer in 1,719 white, African-American and Asian-American families in the United States and Canada. Cancer Causes Control 13 (5): 471-82, 2002.
    66. Cui J, Staples MP, Hopper JL, et al.: Segregation analyses of 1,476 population-based Australian families affected by prostate cancer. Am J Hum Genet 68 (5): 1207-18, 2001.
    67. Conlon EM, Goode EL, Gibbs M, et al.: Oligogenic segregation analysis of hereditary prostate cancer pedigrees: evidence for multiple loci affecting age at onset. Int J Cancer 105 (5): 630-5, 2003.
    68. Valeri A, Briollais L, Azzouzi R, et al.: Segregation analysis of prostate cancer in France: evidence for autosomal dominant inheritance and residual brother-brother dependence. Ann Hum Genet 67 (Pt 2): 125-37, 2003.
    69. Pakkanen S, Baffoe-Bonnie AB, Matikainen MP, et al.: Segregation analysis of 1,546 prostate cancer families in Finland shows recessive inheritance. Hum Genet 121 (2): 257-67, 2007.

    This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http:// cancer .gov or call 1-800-4-CANCER.

    WebMD Public Information from the National Cancer Institute

    Last Updated: May 28, 2015
    This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
    1 | 2 | 3 | 4 | 5 | 6 | 7 | 8
    1 | 2 | 3 | 4 | 5 | 6 | 7 | 8
    Next Article:

    Today on WebMD

    man with doctor
    Symptoms, risks, treatments
    man coughing
    Men shouldn’t ignore
    prostate cancer cells
    What does this diagnosis mean?
    doctor and male patient
    Is it worth it?
    cancer fighting foods
    15 Cancer Symptoms Men Ignore
    Prostate Enlarged
    Picture Of The Prostate
    Prostate Cancer Quiz
    screening tests for men
    Prostate Cancer Symptoms
    Vitamin D