Study Finds More Genes Implicated in Breast and Ovarian Cancer Risk

For decades, the only genes tested for breast cancer risk were BRCA1 and BRCA2. Advances in genetic testing for hereditary cancer risk now enable clinicians to use multiple-gene panels to identify mutations. These panels have identified mutations in other cancer-associated genes in 5% to 15% of BRCA1/2-negative patients with suspected hereditary breast and ovarian cancer (HBOC) syndrome—more than doubling the mutation detection rate.

Researchers analyzed data from a commercial laboratory database of 95,561 women tested clinically for hereditary cancer risk with a 25-gene, next-generation sequencing panel. They accounted for family history and examined the association between pathogenic mutations and breast or ovarian cancer. A matched case-control analysis was conducted, defining cases as patients with breast or ovarian cancer and controls as women without cancer.

One or more pathogenic mutations were detected in 6775 (7%) of 95,561 women. Eight genes (ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, PTEN, and TP53) were associated with breast cancer, with odds ratios ranging from two-fold to six-fold.

Eleven genes (ATM, BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, NBN, STK11, RAD51C, and RAD51D) were associated with ovarian cancer, with odds ratios ranging from two-fold to 40-fold. The researchers concluded that among the 95,561 women studied, 7% carried a pathogenic mutation in one or more cancer-associated genes. Associated breast and ovarian cancer risks ranged from two- to 40-fold after controlling for family history. They note that these results may better inform cancer risk counseling. The study findings are available here.