There is a broad variation in the risk of developing breast cancer among people who carry the BRCA1 and BRCA2 gene mutation, according to a new article.
BRCA2 carrier status," said lead author Colin Begg, PhD, Chair of the Department of Epidemiology and Biostatistics at Memorial Sloan-Kettering Cancer Center, "and the risks in carriers and their relatives must be influenced by other risk factors."
BRCA1 and BRCA2 are gene mutations that predispose carriers to breast cancer. The magnitude of the risk of breast cancer in BRCA1 and BRCA2 carriers is critical for guiding decisions concerning cancer prevention options. The risk of breast cancer in BRCA1 and BRCA2 mutation carriers has been examined in many studies, but relatively little attention has been paid to the degree to which the risk may vary among carriers, according to background information in the article.
Colin B. Begg, Ph.D., of Memorial Sloan-Kettering Cancer Center, New York, and colleagues conducted an investigation to determine the extent to which risks of BRCA1 and BRCA2 carriers vary with respect to observable and unobservable characteristics. Participants in the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study, who were previously diagnosed with unilateral breast cancer (affecting only one side) or contralateral breast cancer (affecting the opposite side of an initial breast cancer), were genotyped for mutations in BRCA1 and BRCA2. All participants had their initial breast cancer diagnosed during the period from January 1985 through December 2000, before the age of 55.
"Among the 1,394 participants with unilateral breast cancer, 73 (5.2 percent) were identified as carriers of deleterious mutations (42 with BRCA1 and 31 with BRCA2)," the authors report. "Among the 704 participants with contralateral breast cancer, 108 (15.3 percent) were identified as carriers of deleterious mutations (67 with BRCA1 and 41 with BRCA2)."
Among relatives of BRCA1 and BRCA2 carriers, risk was significantly associated with a younger age at diagnosis in the proband (the family member through whom a family's medical history comes to light). There was a trend toward higher risk for relatives of participants with contralateral breast cancer vs. unilateral breast cancer participants. "In addition, there were significant differences in risk between carrier families after adjusting for these observed characteristics," the authors write.
Population-based screening for BRCA1 and BRCA2 mutations is not recommended at this time. But the authors point out that in the future, as technology advances and genotyping costs are reduced, widespread genetic screening for important risk factors for breast cancer and other diseases may become routine and is likely to serve as the foundation for tailored risk reduction interventions.
"For this reason, accurate estimation of the risks conferred in the population and identification of important sources of variation in these risks constitute important scientific goals with significant implications for the clinical management of female carriers of BRCA1 and BRCA2 mutations," the authors conclude.
Journal reference: JAMA. 2008;299(2):194-201.
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