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    Genetics of Prostate Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Genes With Potential Clinical Relevance in Prostate Cancer Risk

    Table 9. Case-Control Studies in Varied Populations ofBRCA1andBRCA2and Prostate Cancer Risk continued...

    These data suggest that prostate cancer risk in BRCA1/2 mutation carriers varies with the location of the mutation (i.e., there is a correlation between genotype and phenotype).[17,18,20] These observations might explain some of the inconsistencies encountered in prior studies of these associations, since varied populations may have differences in the proportion of persons with specific pathogenic BRCA1/2 mutations.

    Several case series have also explored the role of BRCA1 and BRCA2 mutations and prostate cancer risk.

    Table 10. Case Series ofBRCA1andBRCA2and Prostate Cancer Risk

    Study Population Mutation Frequency (BRCA1) Mutation Frequency (BRCA2) Prostate Cancer Risk (BRCA1) Prostate Cancer Risk (BRCA2) Comments
    CI = confidence interval; MLPA = multiplex ligation-dependent probe amplification; RR = relative risk.
    a Estimate calculated using relative risk data in UK general population.
    Agalliu et al. (2007)[21] 290 men (white, n = 257; African American, n = 33) diagnosed with prostate cancer <55 y and unselected for family history Not assessed 2 (0.69%) Not assessed RR, 7.8 (95% CI, 1.8-9.4) No mutations were found in African American men.
    The two men with a mutation reported no family history of breast cancer or ovarian cancer.
    Agalliu et al. (2007)[22] 266 individuals from 194 hereditary prostate cancer families, including 253 men affected with prostate cancer; median age at prostate cancer diagnosis: 58 y Not assessed 0 (0%) Not assessed Not assessed 31 nonsynonymous variations were identified; no truncating or deleterious mutations were detected.
    Tryggvadóttir et al. (2007)[23] 527 men diagnosed with prostate cancer between 1955 and 2004 Not assessed 30/527 (5.7%) carried the Icelandic founder mutation 999del5 Not assessed Not assessed TheBRCA2999del5 mutation was associated with a lower mean age at prostate cancer diagnosis (69 vs. 74 y;P = .002)
    Kote-Jarai et al. (2011)[24] 1,832 men diagnosed with prostate cancer between ages 36 and 88 y who participated in the UK Genetic Prostate Cancer Study Not assessed Overall: 19/1,832 (1.03%) Not assessed RR, 8.6a(95% CI, 5.1-12.6) MLPA was not used; therefore, the mutation frequency may be an underestimate, given the inability to detect large genomic rearrangements.
    Prostate cancer diagnosed ≤55 y: 8/632 (1.27%)
    Leongamornlert et al. (2012)[25] 913 men with prostate cancer who participated in the UK Genetic Prostate Cancer Study; included 821 cases diagnosed between ages 36 and 65 y, regardless of family history, and 92 cases diagnosed >65 y with a family history of prostate cancer All cases: 4/886 (0.45%) Not assessed RR, 3.75a(95% CI, 1.02-9.6) Not assessed Quality-control assessment after sequencing excluded 27 cases, resulting in 886 included in the final analysis.
    Cases ≤65 y: 3/802 (0.37%)
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