Variance in BRCA1, BRCA2 mutations appear to be behind differing risks of breast and ovarian cancers

by Bruce Slyvester: Among a large group of women who carry disease-associated mutations in BRCA1 or BRCA2 genes, genetic mutations appear to be associated with significantly different risks of developing breast and ovarian cancers, researchers reported in the April 7 issue of JAMA/Journal of the American Medical Association.

“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 BRCA1/2mutation carriers, but further systematic studies will be required to determine the absolute cancer risks associated with different mutations,” the authors wrote.

As background, they noted that women with inherited mutations in BRCA1 or BRCA2 (BRCA1/2) are at an elevated risk of breast and ovarian cancers, but, to date, research has not established firmly how cancer risks differ by BRCA1/2 mutation type.

Timothy R. Rebbeck, Ph.D., Professor of Epidemiology, Department of Biostatistics and Epidemiology  at 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 any differences in the risk of development of breast and ovarian cancer.

The international study included 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations.

They reported that among BRCA1 mutation carriers, 9,052 subjects (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 subjects (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.

The investigators identified regions and mutations in BRCA1 and BRCA2 that correlated to a higher risk of ovarian cancer, and other regions and mutations that correlated to a higher risk of breast cancer.

Prior research has indicated that, up to age 70, a BRCA1 mutation correlates to a 59 percent risk of breast cancer and a 34 percent risk for ovarian cancer. But the new findings suggest that women carrying a specific subset of BRCA mutations most commonly present in the Ashkenazi Jewish population, for example, have a 69 percent risk of breast cancer and a 26 percent risk of ovarian cancer.

The authors concluded, “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 andBRCA2 mutations.”