Global Study Turns Up 12 More Genetic Variants That Increase Ovarian Cancer Risk

Global Study Turns Up 12 More Genetic Variants That Increase Ovarian Cancer Risk

A search for differences in the DNA of almost 100,000 people, including 17,000 with epithelial ovarian cancer, has identified 12 genetic variants that increase the risk of developing the disease.

Researchers also confirmed that 18 variants they had previously identified were indeed associated with ovarian cancer.

The study, “Twelve new susceptibility loci for different histotypes of epithelial ovarian cancer,” was published in the journal Nature Genetics.

“Ovarian cancer is clearly a very complex disease,” Dr. Catherine Phelan of the Moffitt Cancer Center in Tampa, Florida, said in a press release. “Even the 30 risk variants that we now know increase the risk of developing the disease account for just a small fraction of the inherited component. We believe that there will likely be many more genetic variants involved, each with extremely small effects. Most of these are likely to be common, but some will be rare.”

The OncoArray Consortium, led by scientists in the United States, the United Kingdom, and Australia, compared the DNA of more than 25,000 epithelial ovarian cancer patients with the DNA of nearly 41,000 healthy controls. The study also covered 31,000 women with the BRCA1 and BRCA2 mutations, which are associated with both breast cancer and ovarian cancer.

An analysis of almost 4,000 epithelial ovarian cancer patients led to the researchers finding 12 previously unknown DNA variants associated with the risk of developing epithelial ovarian cancer. It also confirmed that the 18 previously known variants were connected with the disease.

Risk is a measure of how likely a person with a particular characteristic, such as a genetic variant, will develop a disease, compared with people without it.

The latest findings indicate there are at least 30 known genetic variants associated with epithelial ovarian cancer. Together, they account for 6.5 percent of the inherited component of the risk of developing the cancer.

“We know that a woman’s genetic make-up accounts for about one third of her risk of developing ovarian cancer. This is the inherited component of disease risk,” said Professor Paul Pharoah of the University of Cambridge, one of the lead authors of the study. “We’re less certain of environmental factors that increase our risk, but we do know that several factors reduce the risk of ovarian cancer, including taking the oral contraceptive pill, having your tubes tied and having children.”

“In some ways, the hard work starts now,” said Dr. Simon Gayther of the Cedars-Sinai Medical Center in Los Angeles. “We really have little idea of the functional effect these variants have at the molecular or cellular level, and so there are few clues as to how they might affect risk. If we can understand how they work, we will be in a better position to treat — and possibly prevent — ovarian cancer.”

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