Common variation in the BRCA1 gene and prostate cancer risk.

Published

Journal Article

Rare inactivating mutations in the BRCA1 gene seem to play a limited role in prostate cancer. To our knowledge, however, no study has comprehensively assessed the role of other BRCA1 sequence variations (e.g., missense mutations) in prostate cancer. In a study of 817 men with and without prostate cancer from 323 familial and early-onset prostate cancer families, we used family-based association tests and conditional logistic regression to investigate the association between prostate cancer and single nucleotide polymorphisms (SNPs) tagging common haplotype variation in a 200-kb region surrounding (and including) the BRCA1 gene. We also used the Genotype-Identity-by-Descent Sharing Test to determine whether our most strongly associated SNP could account for prostate cancer linkage to chromosome 17q21 in a sample of 154 families from our previous genome-wide linkage study. The strongest evidence for prostate cancer association was for a glutamine-to-arginine substitution at codon 356 (Gln(356)Arg) in exon 11 of the BRCA1 gene. The minor (Arg) allele was preferentially transmitted to affected men (P = 0.005 for a dominant model), with an estimated odds ratio of 2.25 (95% confidence interval, 1.21-4.20). Notably, BRCA1 Gln(356)Arg is not in strong linkage disequilibrium with other BRCA1 coding SNPs or any known HapMap SNP on chromosome 17. In addition, Genotype-Identity-by-Descent Sharing Test results suggest that Gln(356)Arg accounts (in part) for our prior evidence of prostate cancer linkage to chromosome 17q21 (P = 0.022). Thus, we have identified a common, nonsynonymous substitution in the BRCA1 gene that is associated with and linked to prostate cancer.

Full Text

Duke Authors

Cited Authors

  • Douglas, JA; Levin, AM; Zuhlke, KA; Ray, AM; Johnson, GR; Lange, EM; Wood, DP; Cooney, KA

Published Date

  • July 2007

Published In

Volume / Issue

  • 16 / 7

Start / End Page

  • 1510 - 1516

PubMed ID

  • 17585057

Pubmed Central ID

  • 17585057

International Standard Serial Number (ISSN)

  • 1055-9965

Digital Object Identifier (DOI)

  • 10.1158/1055-9965.EPI-07-0137

Language

  • eng

Conference Location

  • United States