A new study conservatively estimates that one in five women with ovarian cancer has inherited genetic mutations that increase the risk of the disease, according to research at Washington University School of Medicine in St. Louis.
Most women in the study would have been unaware of a genetic predisposition to ovarian cancer because they didn’t have strong family histories that suggested it.
The research, published Jan. 22 in Nature Communications, 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 429 women with ovarian cancer that appeared to develop sporadically, meaning the women did not have known family histories of the disease.
“Using advanced genomic analysis, we found that 20 percent 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 the School of Medicine and a research member of Siteman Cancer Center. “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.â€
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 aren’t diagnosed until the cancer has spread, leading to a poor five-year survival rate of 43 percent.
Women with ovarian cancer in the study did not have known family histories of breast or 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, and 90 percent were Caucasian.
The researchers, including Washington University first authors Krishna Kanchi, Kimberly Johnson, PhD, and Charles Lu, PhD, 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, while others occurred in genes that have never been linked to the disease.