A new study conservatively estimates that 1 in 5 women with ovarian cancer have inherited genetic mutations that increase the risk of the disease. Most women in the study would have been unaware of a genetic predisposition to ovarian cancer because they did not have strong family histories that suggested it.

The research, published in Nature Communications (2014; doi:10.1038/ncomms4156), is the first large-scale analysis of the combined contributions of inherited and acquired mutations in a major cancer type. The inherited mutations by themselves are unlikely to cause ovarian cancer but may conspire with other genetic changes acquired over a woman’s lifetime to tip the balance toward cancer, the researchers said.

Earlier studies that have looked at inherited susceptibility to ovarian cancer have focused on women with known family histories of the disease. For the current study, however, the researchers studied tumors from 429 women with ovarian cancer. Their cases were selected without regard to whether the women had family histories of breast cancer, ovarian cancer, or rare cancer syndromes, all of which can increase the odds of developing ovarian tumors. The women ranged in age from 26 to 89 years, and 90% were white.

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“Using advanced genomic analysis, we found that 20% of women with ovarian cancer had inherited mutations in a gene pathway known to be important in inherited breast and ovarian cancer. That number seems pretty high,” explained senior author Li Ding, PhD, assistant director at The Genome Institute at Washington University School of Medicine in St. Louis, Missouri. “This tells us that we need to find better ways to screen women for ovarian cancer, even if they don’t have family histories of the disease.”

Ovarian cancer strikes an estimated 22,000 women annually. Its symptoms are nonspecific and include bloating, pelvic pain, and frequently feeling the need to urinate. Most women are not diagnosed until the cancer has spread, leading to a poor 5-year survival rate of 43%.

The researchers performed a genetic analysis of each woman’s tumor and her own DNA, taken from a skin sample. By comparing the genetic sequences side-by-side, they identified the acquired mutations in individual tumor samples. In addition, by comparing the patients’ DNA samples with the DNA of 557 women who did not have ovarian cancer and served as controls, the researchers found inherited mutations.

In all, the scientists identified 222 inherited genetic variants that increase the risk of ovarian cancer. Some occurred in genes already known to be associated with a genetic predisposition to ovarian cancer, such as BRCA1 and BRCA2, whereas others occurred in genes that have never been linked to the disease.

The inherited mutations identified as part of the study involved major genetic changes where large chunks of the protein-coding sequences were truncated, or shortened, disrupting the function of key proteins such as those that normally keep cell division in check or repair mistakes in DNA.

“With more research, we expect to find additional mutations linked to hereditary ovarian cancer,” Ding said. “Thus, 20% is a conservative estimate.”