JAMA: In a study that involved more than 31,000 women who are carriers of disease-associated mutations in the BRCA1 or BRCA2 genes, researchers identified mutations that were associated with significantly different risks of breast and ovarian cancers, findings that may have implications for risk assessment and cancer prevention decision making among carriers of these mutations, according to a study in the April 7 issue of JAMA.
Women who have inherited mutations in BRCA1 or BRCA2 (BRCA1/2) have an increased risk of breast and ovarian cancers. Little has been known about how cancer risks differ by BRCA1/2 mutation type, according to background information in the article.
Timothy R. Rebbeck, Ph.D., of the Perelman School of Medicine at the
University of Pennsylvania, Philadelphia, and colleagues evaluated
whether BRCA1 and BRCA2 mutation type or location is
associated with variation in breast and ovarian cancer risk. The study
included 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 33 countries.
Among BRCA1 mutation carriers, 9,052 women (46 percent) were
diagnosed with breast cancer, 2,317 (12 percent) with ovarian cancer,
1,041 (5 percent) with breast and ovarian cancer, and 7,171 (37 percent)
without cancer. Among BRCA2 mutation carriers, 6,180 women (52
percent) were diagnosed with breast cancer, 682 (6 percent) with ovarian
cancer, 272 (2 percent) with breast and ovarian cancer, and 4,766 (40
percent) without cancer. Analysis of the data indicated that the risk of
breast and ovarian cancer varied by the type and location of BRCA1/2 mutations.
“This study is the first step in defining differences in risk associated with location and type of BRCA1 and BRCA2
mutations. Pending additional mechanistic insights into the observed
associations, knowledge of mutation-specific risks could provide
important information for clinical risk assessment among BRCA1/2
mutation carriers, but further systematic studies will be required to
determine the absolute cancer risks associated with different
mutations,” the authors write.
“It is yet to be determined what level of absolute risk change will influence decision making among carriers of BRCA1/2
mutations. Additional research will be required to better understand
what level of risk difference will change decision making and standards
of care, such as preventive surgery, for carriers of BRCA1 and BRCA2 mutations.”
(doi:10.1001/jama.2014.5985; Available pre-embargo to the media at http://media.jamanetwork.com)
Please see the article for additional information, including other
authors, author contributions and affiliations, financial disclosures,
funding and support, etc.