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Genetics of Prostate Cancer (PDQ®)

  • Posted: 11/20/2003
  • Updated: 07/18/2014

Table 3. Case-Control Studies in Genes With Some Association With Prostate Cancer Risk

Gene Location Study Population Controls Prostate Cancer Associations Comments  
AJ = Ashkenazi Jewish; CI = confidence interval; HR = hazard ratio; OMIM = Online Mendelian Inheritance in Man; OR = odds ratio; PSA = prostate-specific antigen; SNP = single nucleotide polymorphism.
AMACR (OMIM)5p13.3Zheng et al. (2002) [165]159 U.S. men with familial prostate cancer and 245 men with sporadic prostate cancer211 men without prostate cancer who are participants in a prostate cancer screening programNot assessedGenotype frequencies that compared familial prostate cancer cases to unaffected controls found four missense variants associated with familial prostate cancer (M9V, G1157D, S291L, and K277E).
Daugherty et al. (2007) [166]1,318 U.S. men aged <55 y with prostate cancer (1,211 non-Hispanic whites and 107 non-Hispanic blacks) unselected for family history1,842 U.S. men without prostate cancer who participated in a prostate cancer screening program (1,433 non-Hispanic whites and 409 non-Hispanic blacks)No association was detected between any of the SNPs (M9V, IVS+169G>T, D175G, S201L, Q239H, IVS4+3803C>G, and K277E) and prostate cancer.Risk of prostate cancer was reduced in men who regularly used ibuprofen who also had specific alleles in four SNPs (M9V, D175G, S201L, and K77E) or a specific six-SNP haplotype (TGTGCG).
Levin et al. (2007) [167]449 U.S. white men with familial prostate cancer from 332 familial and early-onset prostate cancer families394 unaffected brothers of the men with prostate cancerSNP rs3195676 (M9V):
OR, 0.58 (95% CI, 0.38–0.90; P = .01 for a recessive model)
NBS1 (OMIM)8q21Hebbring et al. (2006) [168]1,819 U.S. and European men with familial prostate cancer from 909 families and 1,218 U.S. and European men with sporadic prostate cancer697 controls consisting of a mix of U.S. and European population-based controls and unaffected men from prostate cancer families657del5 was not detected in the control population; therefore, testing for an association was not possible.657del5 had a carrier frequency of 0.22% (2 of 909) for familial prostate cancer and 0.25% (3 of 1,218) for sporadic prostate cancer.
Cybulski et al. (2013) [169]3,750 Polish men with prostate cancer3,956 Polish men with no history of cancer675del5: OR, 2.5 (95% CI, 1.5–4.0; P = .0003)NBS1 mutations were associated with a higher mortality (HR, 1.85) and lower 5-year survival (HR, 2.08).
Prostate cancer diagnosed <60 y: OR, 3.1 (95% CI, 1.5–6.4; P = .003)
Familial prostate cancer: OR, 4.3 (95% CI, 2.0–9.0; P = .0001)
KLF6 (OMIM)10p15Narla et al. (2005) [170]1,253 U.S. men with sporadic prostate cancer and 882 men with familial prostate cancer from 294 unrelated families1,276 men with no cancer historyIVS1-27G>A:
Familial cases: OR, 1.61 (95% CI, 1.20–2.16; P = .01)
Sporadic cases: OR, 1.41 (95% CI, 1.08–2.00; P = .01)
Bar-Shira et al. (2006) [171]402 Israeli men with prostate cancer (251 AJ, 151 non-AJ)300 Israeli women aged 20–45 y (200 AJ, 100 non-AJ)IVS1-27G>A:
AJ only: OR, 0.60 (95% CI, 0.35–1.03; P = .047)
Combined cohort: OR, 0.64 (95% CI, 0.42–0.98; P = .047)
EMSY (OMIM)11q13.5Nurminen et al. (2011) [172]Initial Screen: 184 Finnish men with familial prostate cancer923 male blood donors from the Finnish Red Cross with no cancer historyIVS6-43A>G:IVS6-43A>G also associated with increased risk of aggressive prostate cancer (PSA ≥20 or Gleason score ≥7) in cases unselected for family history (OR, 6.5; 95% CI, 1.5–28.4; P = .002).
Validation: 2,113 unselected prostate cancer casesFamilial cases: OR, 7.5 (95% CI, 1.3–45.5; P = .02)
CHEK2 (OMIM)22q12.1Dong et al. (2003) [173]84 prostate cancer tumors; 92 prostate cancer tumors diagnosed in men younger than 59 y; 400 U.S. men with prostate cancer and no prostate cancer family history; 298 men with prostate cancer from 149 families (two men per family)510 U.S. men without prostate cancer with a negative prostate cancer screening exam18 CHEK2 mutations were identified in 4.8% (28 of 578) of prostate cancer patients, 0 of 423 unaffected men, and 9 of 149 prostate cancer families.157T was detected in equal numbers of cases and controls and was therefore reported to likely represent a polymorphism.
Cybulski et al. (2013) [169]3,750 Polish men with prostate cancer3,956 Polish men with no history of cancerAny CHEK2 mutation: OR, 1.9 (95% CI, 1.6–2.2; P < .0001)
Prostate cancer diagnosed <60 y: OR, 2.3 (95% CI, 1.8–3.1; P < .0001)
Familial prostate cancer: OR, 2.7 (95% CI, 2.0–3.7; P < .0001)


  1. Zheng SL, Chang BL, Faith DA, et al.: Sequence variants of alpha-methylacyl-CoA racemase are associated with prostate cancer risk. Cancer Res 62 (22): 6485-8, 2002.  [PUBMED Abstract]

  2. Daugherty SE, Shugart YY, Platz EA, et al.: Polymorphic variants in alpha-methylacyl-CoA racemase and prostate cancer. Prostate 67 (14): 1487-97, 2007.  [PUBMED Abstract]

  3. Levin AM, Zuhlke KA, Ray AM, et al.: Sequence variation in alpha-methylacyl-CoA racemase and risk of early-onset and familial prostate cancer. Prostate 67 (14): 1507-13, 2007.  [PUBMED Abstract]

  4. Hebbring SJ, Fredriksson H, White KA, et al.: Role of the Nijmegen breakage syndrome 1 gene in familial and sporadic prostate cancer. Cancer Epidemiol Biomarkers Prev 15 (5): 935-8, 2006.  [PUBMED Abstract]

  5. Cybulski C, Wokołorczyk D, Kluźniak W, et al.: An inherited NBN mutation is associated with poor prognosis prostate cancer. Br J Cancer 108 (2): 461-8, 2013.  [PUBMED Abstract]

  6. Narla G, Difeo A, Reeves HL, et al.: A germline DNA polymorphism enhances alternative splicing of the KLF6 tumor suppressor gene and is associated with increased prostate cancer risk. Cancer Res 65 (4): 1213-22, 2005.  [PUBMED Abstract]

  7. Bar-Shira A, Matarasso N, Rosner S, et al.: Mutation screening and association study of the candidate prostate cancer susceptibility genes MSR1, PTEN, and KLF6. Prostate 66 (10): 1052-60, 2006.  [PUBMED Abstract]

  8. Nurminen R, Wahlfors T, Tammela TL, et al.: Identification of an aggressive prostate cancer predisposing variant at 11q13. Int J Cancer 129 (3): 599-606, 2011.  [PUBMED Abstract]

  9. Dong X, Wang L, Taniguchi K, et al.: Mutations in CHEK2 associated with prostate cancer risk. Am J Hum Genet 72 (2): 270-80, 2003.  [PUBMED Abstract]