Skip to main content

Advertisement

Log in

Review: Inherited predisposition to prostate cancer

  • Published:
European Journal of Epidemiology Aims and scope Submit manuscript

Abstract

A genetic component in prostate cancer has been recognized for decades. Through numerous epidemiological and molecular biological studies much evidence has accumulated in favor of a significant but heterogeneous hereditary component in prostate cancer (PCa) susceptibility. At first, segregation analyses supported the view that a number of high-risk loci contributed to the observed Mendelian inheritance of PCa. Consequent mapping efforts yielded several susceptibility loci across the genome. At three of these loci genes have been cloned and mutations identified. Their role in hereditary and sporadic disease, however, is still under debate and probably very modest. The current evidence supports the hypothesis that excess familial risk of PCa is due to the inheritance of multiple moderate-risk genetic variants. Although research on hereditary prostate cancer has improved our knowledge of the genetic etiology of the disease, a lot of questions still remain unanswered. Here, we aim to review the genetic epidemiological research and the mapping efforts in the field of hereditary PCa and the consequent problems that are encountered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Stanford JL, Ostrander EA. Familial prostate cancer. Epidemiol Rev 2001; 23: 19–23.

    PubMed  Google Scholar 

  2. Morganti G, Gianferrari L, Cresseri A, Arrigoni G, Lovati G. Recherches clinico-statistiques et génétiques sur les néoplasies de la prostate. Acta Genet Stat Med 1956; 6: 304–305.

    PubMed  Google Scholar 

  3. 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 1995; 141: 732–740.

    PubMed  Google Scholar 

  4. Goldgar DE, Easton DF, Cannon-Albright LA, Skolnick MH. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst 1994; 86: 1600–1608.

    PubMed  Google Scholar 

  5. Isaacs SD, Kiemeney LA, Baffoe-Bonnie A, Beaty TH, Walsh PC. Risk of cancer in relatives of prostate cancer probands. J Natl Cancer Inst 1995; 87: 991–996.

    PubMed  Google Scholar 

  6. Gronberg H, Bergh A, Damber JE, Emanuelsson M. Cancer risk in families with hereditary prostate carcinoma. Cancer 2000; 89: 1315–1321.

    PubMed  Google Scholar 

  7. Matikainen 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 2001; 12: 223–230.

    PubMed  Google Scholar 

  8. Damber L, Gronberg H, Damber JE. Familial prostate cancer and possible associated malignancies: Nationwide register cohort study in Sweden. Int J Cancer 1998; 78: 293–297.

    PubMed  Google Scholar 

  9. Valeri A, Fournier G, Morin V, et al. Early onset and familial predisposition to prostate cancer significantly enhance the probability for breast cancer in first degree relatives. Int J Cancer 2000; 86: 883–887.

    PubMed  Google Scholar 

  10. Keetch DW, Rice JP, Suarez BK, Catalona WJ. Familial aspects of prostate cancer: A case control study. J Urol 1995; 154: 2100–2102.

    PubMed  Google Scholar 

  11. Bratt O, Kristoffersson U, Lundgren R, Olsson H. The risk of malignant tumours in first-degree relatives of men with early onset prostate cancer: A population-based cohort study. Eur J Cancer 1997; 33: 2237–2240.

    PubMed  Google Scholar 

  12. Carter BS, Beaty TH, Steinberg GD, Childs B, Walsh PC. Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci USA 1992; 89: 3367–3371.

    PubMed  Google Scholar 

  13. Gronberg H, Damber L, Damber JE, Iselius L. Segregation analysis of prostate cancer in Sweden: Support for dominant inheritance. Am J Epidemiol 1997; 146: 552–557.

    PubMed  Google Scholar 

  14. Schaid DJ, McDonnell SK, Blute ML, Thibodeau SN. Evidence for autosomal dominant inheritance of prostate cancer. Am J Hum Genet 1998; 62: 1425–1438.

    PubMed  Google Scholar 

  15. Verhage BA, Baffoe-Bonnie AB, Baglietto L, et al. Autosomal dominant inheritance of prostate cancer: A confirmatory study. Urology 2001; 57: 97–101.

    PubMed  Google Scholar 

  16. Cui J, Staples MP, Hopper JL, English DR, McCredie MR, Giles GG. Segregation analyses of 1476 population-based Australian families affected by prostate cancer. Am J Hum Genet 2001; 68: 1207–1218.

    PubMed  Google Scholar 

  17. Gong G, Oakley-Girvan I, Wu AH, et al. Segregation analysis of prostate cancer in 1719 white, African-American, and Asian-American families in the United States and Canada. Cancer Causes Control 2002; 13: 471–482.

    PubMed  Google Scholar 

  18. Ostrander EA, Stanford JL. Genetics of prostate cancer: Too many loci, too few genes. Am J Hum Genet 2000; 67: 1367–1375.

    PubMed  Google Scholar 

  19. Smith JR, Freije D, Carpten JD, et al. Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search. Science 1996; 274: 1371–1374.

    PubMed  Google Scholar 

  20. Gronberg H, Xu J, Smith JR, et al. Early age at diagnosis in families providing evidence of linkage to the hereditary prostate cancer locus (HPC1) on chromosome 1. Cancer Res 1997; 57: 4707–4709.

    PubMed  Google Scholar 

  21. Xu J. Combined analysis of hereditary prostate cancer linkage to 1q24-25: Results from 772 hereditary prostate cancer families from the International Consortium for Prostate Cancer Genetics. Am J Hum Genet 2000; 66: 945–957.

    PubMed  Google Scholar 

  22. Cooney KA, McCarthy JD, Lange E, et al. Prostate cancer susceptibility locus on chromosome 1q: A confirmatory study. J Natl Cancer Inst 1997; 89: 955–959.

    PubMed  Google Scholar 

  23. Hsieh CL, Oakley-Girvan I, Gallagher RP, et al. Re: Prostate cancer susceptibility locus on chromosome 1q: A confirmatory study. J Natl Cancer Inst 1997; 89: 1893–1894.

    PubMed  Google Scholar 

  24. McIndoe RA, Stanford JL, Gibbs M, et al. Linkage analysis of 49 high-risk families does not support a common familial prostate cancer-susceptibility gene at 1q24-25. Am J Hum Genet 1997; 61: 347–353.

    PubMed  Google Scholar 

  25. Eeles RA, Durocher F, Edwards S, et al. Linkage analysis of chromosome 1q markers in 136 prostate cancer families. The Cancer Research Campaign/British Prostate Group UK Familial Prostate Cancer Study Collaborators. Am J Hum Genet 1998; 62: 653–658.

    PubMed  Google Scholar 

  26. Carpten J, Nupponen N, Isaacs S, et al. Germline mutations in the ribonuclease L gene in families showing linkage with HPC1. Nat Genet 2002; 30: 181–184.

    PubMed  Google Scholar 

  27. Berthon P, Valeri A, Cohen-Akenine A, et al. Predisposing gene for early-onset prostate cancer, localized on chromosome 1q42.2-43. Am J Hum Genet 1998; 62: 1416–1424.

    PubMed  Google Scholar 

  28. Xu J, Meyers D, Freije D, et al. Evidence for a prostate cancer susceptibility locus on the X chromosome. Nat Genet 1998; 20: 175–179.

    PubMed  Google Scholar 

  29. Gibbs M, Stanford JL, McIndoe RA, et al. Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36. Am J Hum Genet 1999; 64: 776–787.

    PubMed  Google Scholar 

  30. Berry R, Schroeder JJ, French AJ, et al. Evidence for a prostate cancer-susceptibility locus on chromosome 20. Am J Hum 2000; 67: 82–91.

    Google Scholar 

  31. Xu J, Zheng SL, Hawkins GA, et al. Linkage and association studies of prostate cancer susceptibility: Evidence for linkage at 8p22-23. Am J Hum Genet 2001; 69: 341–350.

    PubMed  Google Scholar 

  32. Cancel-Tassin G, Latil A, Valeri A, et al. PCAP is the major known prostate cancer predisposing locus in families from south and west Europe. Eur J Hum Genet 2001; 9: 135–142.

    PubMed  Google Scholar 

  33. Gibbs M, Chakrabarti L, Stanford JL, et al. Analysis of chromosome 1q42.2-43 in 152 families with high risk of prostate cancer. Am J Hum Genet 1999; 64: 1087–1095.

    PubMed  Google Scholar 

  34. Schleutker J, Matikainen M, Smith J, et al. A genetic epidemiological study of hereditary prostate cancer (HPC) in Finland: Frequent HPCX linkage in families with late-onset disease. Clin Cancer Res 2000; 6: 4810–4815.

    PubMed  Google Scholar 

  35. Bock CH, Cunningham JM, McDonnell SK, et al. Analysis of the prostate cancer-susceptibility locus HPC20 in 172 families affected by prostate cancer. Am J Hum Genet 2001; 68: 795–801.

    PubMed  Google Scholar 

  36. Cancel-Tassin G, Latil A, Valeri A, et al. No evidence of linkage to HPC20 on chromosome 20q13 in hereditary prostate cancer. Int J Cancer 2001; 93: 455–456.

    PubMed  Google Scholar 

  37. Xu J, Zheng SL, Komiya A, et al. Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. Nat Genet 2002; 32: 321–325.

    PubMed  Google Scholar 

  38. Rokman A, Ikonen T, Seppala EH, 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: 1299–1304.

    PubMed  Google Scholar 

  39. Tavtigian SV, Simard J, Teng HF, et al. A strong candidate prostate cancer susceptibility gene at chromosome 17p. Nat Genet 2001; 27: 172–180.

    PubMed  Google Scholar 

  40. Rebbeck TR, Walker AH, Zeigler-Johnson C, et al. Association of HPC2/ELAC2 genotypes and prostate cancer. Am J Hum Genet 2000; 67: 1014–1019.

    PubMed  Google Scholar 

  41. Suarez BK, Gerhard DS, Lin J, et al. Polymorphisms in the prostate cancer susceptibility gene HPC2/ELAC2 in multiplex families and healthy controls. Cancer Res 2001; 61: 4982–4984.

    PubMed  Google Scholar 

  42. Xu J, Zheng SL, Carpten JD, et al. Linkage and Association of HPC2/ELAC2. Am J Hum Genet 2000; 68: 901–911.

    Google Scholar 

  43. Wang L, McDonnell SK, Elkins DA, et al. Role of HPC2/ELAC2 in hereditary prostate cancer. Cancer Res 2001; 61: 6494–6499.

    PubMed  Google Scholar 

  44. Vesprini D, Nam RK, Trachtenberg J, et al. HPC2 Variants and Screen-Detected Prostate Cancer. Am J Hum Genet 2000; 68: 912–917.

    Google Scholar 

  45. Rokman A, Ikonen T, Mononen N, et al. ELAC2/HPC2 involvement in hereditary and sporadic prostate cancer. Cancer Res 2001; 61: 6038–6041.

    PubMed  Google Scholar 

  46. Camp NJ, Tavtigian SV. Meta-analysis of associations of the Ser217Leu and Ala541Thr variants in ELAC2 (HPC2) and prostate cancer. Am J Hum Genet 2002; 71: 1475–1478.

    PubMed  Google Scholar 

  47. Severi G, Giles GG, Southey MC, et al. ELAC2/HPC2 polymorphisms, prostate-specific antigen levels, and prostate cancer. J Natl Cancer Inst 2003; 95: 818–824.

    PubMed  Google Scholar 

  48. Silverman RH. Implications for RNase L in prostate cancer biology. Biochemistry 2003; 42: 1805–1812.

    PubMed  Google Scholar 

  49. Rennert H, Bercovich D, Hubert A, et al. A novel founder mutation in the RNASEL gene, 471delAAAG, is associated with prostate cancer in Ashkenazi Jews. Am J Hum Genet 2002; 71: 981–984.

    PubMed  Google Scholar 

  50. Casey G, Neville PJ, Plummer SJ, et al. RNASEL Arg462Gln variant is implicated in up to 13% of prostate cancer cases. Nat Genet 2002; 32: 581–583.

    PubMed  Google Scholar 

  51. Wang L, McDonnell SK, Elkins DA, et al. Analysis of the RNASEL gene in familial and sporadic prostate cancer. Am J Hum Genet 2002; 71(1): 116–123 (Erratum in: Am J Hum Genet 2002; 71: 449).

    PubMed  Google Scholar 

  52. Platt N, Gordon S. Is the class A macrophage scavenger receptor (SR-A) multifunctional? - The mouse's tale. J Clin Invest 2001; 108: 649–654.

    PubMed  Google Scholar 

  53. Xu J, Zheng SL, Komiya A, et al. Common sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk. Am J Hum Genet 2003; 72: 208–212.

    PubMed  Google Scholar 

  54. Miller DC, Zheng SL, Dunn RL, et al. Germ-line mutations of the macrophage scavenger receptor 1 gene: Association with prostate cancer risk in African-American men. Cancer Res 2003; 63: 3486–3489.

    PubMed  Google Scholar 

  55. Ingles SA, Ross RK, Yu MC, et al. Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor. J Natl Cancer Inst 1997; 89: 166–170.

    PubMed  Google Scholar 

  56. Giovannucci E, Stampfer MJ, Krithivas K, et al. The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc Natl Acad Sci USA 1997; 94: 3320–3323.

    PubMed  Google Scholar 

  57. Stanford JL, Just JJ, Gibbs M, et al. Polymorphic repeats in the androgen receptor gene: Molecular markers of prostate cancer risk. Cancer Res 1997; 57: 1194–1198.

    PubMed  Google Scholar 

  58. Hsing AW, Gao YT, Wu G, et al. Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: A population-based case-control study in China. Cancer Res 2000; 60: 5111–5116.

    PubMed  Google Scholar 

  59. Reichardt JK, Makridakis N, Henderson BE, Yu MC, Pike MC, Ross RK. Genetic variability of the human SRD5A2 gene: Implications for prostate cancer risk. Cancer Res 1995; 55: 3973–3975.

    PubMed  Google Scholar 

  60. Kantoff PW, Febbo PG, Giovannucci E, et al. A polymorphism of the 5alpha-reductase gene and its association with prostate cancer: A case-control analysis. Cancer Epidemiol Biomarkers Prev 1997; 6: 189–192.

    PubMed  Google Scholar 

  61. Lunn RM, Bell DA, Mohler JL, Taylor JA. Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2). Carcinogenesis 1999; 20: 1727–1731.

    PubMed  Google Scholar 

  62. Febbo PG, Kantoff PW, Platz EA, et al. The V89L polymorphism in the 5alpha-reductase type 2 gene and risk of prostate cancer. Cancer Res 1999; 59: 5878–5881.

    PubMed  Google Scholar 

  63. Makridakis NM, Ross RK, Pike MC, et al. Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA. Lancet 1999; 354: 975–978.

    PubMed  Google Scholar 

  64. Verhage BA, Van Houwelingen K, Ruijter TE, Kiemeney LA, Schalken JA. Single-nucleotide polymorphism in the E-cadherin gene promoter modifies the risk of prostate cancer. Int J Cancer 2002; 100: 683–685.

    PubMed  Google Scholar 

  65. Coughlin SS, Hall IJ. A review of genetic polymorphisms and prostate cancer risk. Ann Epidemiol 2002; 12: 182–196.

    PubMed  Google Scholar 

  66. Bratt O, Damber JE, Emanuelsson M, et al. Risk perception, screening practice and interest in genetic testing among unaffected men in families with hereditary prostate cancer. Eur J Cancer 2000; 36: 235–241.

    PubMed  Google Scholar 

  67. Miesfeldt S, Jones SM, Cohn W, et al. Men's attitudes regarding genetic testing for hereditary prostate cancer risk. Urology 2000; 55(1): 46–50.

    PubMed  Google Scholar 

  68. Neal DE, Donovan JL. Prostate cancer: To screen or not to screen. Lancet Oncol 2000; 1: 17–24.

    PubMed  Google Scholar 

  69. Matikainen MP, Schleutker J, Morsky P, Kallioniemi OP, Tammela TL. Detection of subclinical cancers by prostate-specific antigen screening in asymptomatic men from high-risk prostate cancer families. Clin Cancer Res 1999; 5: 1275–1279.

    PubMed  Google Scholar 

  70. Carter BS, Bova GS, Beaty TH, et al. Hereditary prostate cancer: Epidemiologic and clinical features. J Urol 1993; 150: 780–797.

    Google Scholar 

  71. Bastacky SI, Wojno KJ, Walsh PC, Carmichael MJ, Epstein JI. Pathological features of hereditary prostate cancer. J Urol 1995; 153: 987–992.

    PubMed  Google Scholar 

  72. Bova GS, Partin AW, Isaacs SD, et al. Biological aggressiveness of hereditary prostate cancer: Long-term evaluation following radical prostatectomy. J Urol 1998; 160: 660–663.

    PubMed  Google Scholar 

  73. Keetch DW, Humphrey PA, Smith DS, Stahl D, Catalona WJ. Clinical and pathological features of hereditary prostate cancer. J Urol 1996; 155: 1841–1843.

    PubMed  Google Scholar 

  74. Grönberg H, Damber L, Tavelin B, Damber JE. No differences in survival between sporadic, familial and hereditary prostate cancer. Brit J Urol 1998; 82: 564–567.

    PubMed  Google Scholar 

  75. Grönberg H, Isaacs SD, Isaacs MS, et al. Characteristics of prostate cancer in families potentially linked to the hereditary prostate cancer 1 (HPC1) locus. JAMA 1997; 278: 1251–1255.

    PubMed  Google Scholar 

  76. Laniado ME. Prostate cancer potentially linked to the HPC1 gene. JAMA 1997; 278: 1251–1255.

    PubMed  Google Scholar 

  77. Walther MM. Prostate cancer potentially linked to the HPC1 gene. JAMA 1997; 278: 1251–1255.

    PubMed  Google Scholar 

  78. Valeri A, Azzouzi R, Drelon E, et al. Early-onset hereditary prostate cancer is not associated with specific clinical and biological features. Prostate 2000; 45: 66–71.

    PubMed  Google Scholar 

  79. Bratt O, Damber JE, Emanuelsson M, Grönberg H. Hereditary prostate cancer: Clinical characteristics and survival. J Urol 2002; 167: 2423–2426.

    PubMed  Google Scholar 

  80. Witte JS, Goddard KA, Conti DV, et al. Genomewide scan for prostate cancer-aggressiveness loci. Am J Hum Genet 2000; 67: 92–99.

    PubMed  Google Scholar 

  81. Walsh PC, Partin AW. Family history facilitates the early diagnosis of prostate carcinoma. Cancer 1997; 80: 1871–1874.

    PubMed  Google Scholar 

  82. 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 2000 Aug 15; 60(16): 4513–4518.

    PubMed  Google Scholar 

  83. Edwards SM, Kote-Jarai Z, Meitz J, et al. Cancer Research UK/Bristish Prostate Group UK Familial Prostate Cancer Study Collaborators; British Association of Urological Surgeons Section of Oncology. Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. Am J Hum Genet 2003; 72: 1–12.

    PubMed  Google Scholar 

  84. Bonn D. Prostate-cancer screening targets men with BRCA mutations. Lancet Oncol 2002; 3: 714.

    PubMed  Google Scholar 

  85. Sinclair CS, Berry R, Schaid D, Thibodeau SN, Couch FJ. BRCA1 and BRCA2 have a limited role in familial prostate cancer. Cancer Res 2000; 60: 1371–1375.

    PubMed  Google Scholar 

  86. Nelson PS, Stanford JL, Ostrander EA. Prostate cancer research in the post-genome era. Epidemiol Rev 2001; 23: 187–190.

    PubMed  Google Scholar 

  87. DeRisi J, Penland L, Brown PO, et al. Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet 1996; 14: 457–460.

    PubMed  Google Scholar 

  88. Kononen J, Bubendorf L, Kallioniemi A, et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 1998; 4: 844–847.

    PubMed  Google Scholar 

  89. Ingles SA, Coetzee GA, Ross RK, et al. Association of prostate cancer with vitamin D receptor haplotypes in African-Americans. Cancer Res 1998; 58: 1620–1623.

    PubMed  Google Scholar 

  90. Blazer DG III, Umbach DM, Bostick RM, Taylor JA. Vitamin D receptor polymorphisms and prostate cancer. Mol Carcinog 2000; 27: 18–23.

    PubMed  Google Scholar 

  91. Taylor JA, Hirvonen A, Watson M, Pittman G, Mohler JL, Bell DA. Association of prostate cancer with vitamin D receptor gene polymorphism. Cancer Res 1996; 56: 4108–4110.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Verhage, B.A., Kiemeney, L.A. Review: Inherited predisposition to prostate cancer. Eur J Epidemiol 18, 1027–1036 (2003). https://doi.org/10.1023/A:1026101914592

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026101914592

Navigation