Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian

Cancer. 2015 Jan 15;121(2):269-75. doi: 10.1002/cncr.29041. Epub 2014 Sep 15.

Abstract

Background: Previous studies have reported additional cancers associated with BRCA mutations; however, the type, magnitude of risk, and sex differences remain to be clarified. The purpose of this study was to evaluate the incidence of cancers other than breast and ovarian cancer in known mutation carriers.

Methods: An institutional review board-approved study identified 1072 patients who had genetic counseling at the authors' institution and tested positive for a deleterious BRCA mutation. The expected number of cancer cases was calculated from the number of individuals in the study sample multiplied by the cancer incidence rates for the general population. The expected and observed numbers of cases were calculated in 5-year intervals to accommodate different age-related incidence rates. Standardized incidence ratios (SIRs) for each cancer type were calculated.

Results: Among the 1072 mutation carriers, 1177 cancers of 30 different cancer types were identified. Individuals with a BRCA1 mutation did not have a significant increase in cancers other than breast and ovarian cancer; however, a trend in melanoma was observed. Individuals with a BRCA2 mutation had significantly higher numbers of observed cases versus expected cases for pancreatic cancer in both men and women (SIR, 21.7; 95% confidence interval [CI], 13.1-34.0; P < .001) and for prostate cancer in men (SIR, 4.9; 95% CI, 2.0-10.1; P = .002).

Conclusions: The results of this study uphold the current recommendations for hereditary breast and ovarian cancer screening of cancers other than breast and ovarian cancer by the National Comprehensive Cancer Network. Larger cohorts and collaborations are needed to further verify these findings.

Keywords: BRCA mutation; genetics; hereditary breast and ovarian cancer syndrome; pancreatic cancer; prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast Neoplasms / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Heterozygote*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Mutation*
  • Ovarian Neoplasms / genetics
  • Pancreatic Neoplasms / epidemiology*
  • Pancreatic Neoplasms / ethnology
  • Pancreatic Neoplasms / genetics*
  • Risk Assessment
  • Risk Factors
  • United States / epidemiology

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human