Genetic Variation in the BRCA2 Gene and Prostate Cancer Risk in the Health Professionals Follow-Up Study (HPFS) and Physicians' Health Study (PHS)

Abstract

There is an urgent need to identify biomarkers that may be linked to aggressive and early-onset forms of prostate cancer. Previous studies have identified a link between mutations in the BRCA2 tumor suppressor gene and prostate cancer. The primary goal of this study was to assess the role of genetic variation in the BRCA2 gene on the risk of prostate cancer, both overall risk and risk of more advanced or aggressive disease. This study utilized genotype data from nested case-control studies as part of the Health Professionals Follow-up Study (HPFS) and the Physicians’ Health Study (PHS), and identified 136 single nucleotide polymorphisms (SNPs) in the BRCA2 gene. We calculated per-allele odds ratios (ORs) and 95% confidence intervals (95% CIs) using unconditional logistic regression, adjusted for the matching factors for each of the SNPs.

This study failed to identify SNPs within the BRCA2 gene that were statistically significantly associated with risk of prostate cancer. We observed no strong association across all cohorts between genetic variation in BRCA2 and risk of prostate cancer. One SNP, rs10492396, was found to be associated with an increased risk of prostate cancer, only in the HPFS. None of the SNPs were associated with risk of fatal prostate cancer. Further studies are needed to understand the potential role of variation in the tumor suppressor gene BRCA2 and prostate cancer risk.