2 studies find new genetic links to ovarian cancer risk

An international consortium of scientists has discovered new genetic variants in five regions of the genome that affect the risk of ovarian cancer in the general population, according to two separate studies published today (Sunday), online in Nature Genetics.

The consortium, including scientists from the U.S., Europe, Canada and Australia, based the new work on their earlier research comparing 10,283 women with ovarian cancer to 13,185 women without the disease. That effort had found a stretch of DNA on chromosome 9 containing single DNA letter variations (SNPs) associated with ovarian cancer risk.

The researchers have now found additional stretches of DNA on chromosomes 2, 3, 8, 17 and 19 after grouping patients according to the type of ovarian cancer they had developed. Four out of five of the new DNA variations were more common in women who had developed the most common and aggressive form of disease, known as serous ovarian cancer.

Andrew Berchuck, MD, professor of gynecologic oncology at Duke University Medical Center and head of the steering committee of the international Ovarian Cancer Association Consortium (OCAC), says the associations of these genetic variants with ovarian cancer were discovered using genome-wide association studies (GWAS).

"Since the critical validation of these findings was performed by a large consortium of investigators from around the world, we see this research as a triumph of science without borders for the benefit of women everywhere."

Ovarian cancer is the fifth most common cancer among women in developed countries, and often detected in later stages when the chances of cure are small. As a result, the disease claims more lives in the U.S. than all other gynecological cancers combined. Every year, about 13,000 women in the U.S. and 130,000 worldwide die from the disease.

"These latest findings raise the possibility that in the future, women in the general population who are at the greatest risk of developing ovarian cancer because they carry these newly discovered DNA variants can be identified and given closer surveillance to look for early signs of ovarian cancer when it is most treatable," says Berchuck. "It also suggests that preventive approaches could be targeted towards these women."

Ellen Goode*, PhD, a genetic epidemiologist at the Mayo Clinic College of Medicine and the lead author of one of the studies, says "additional research will be required to learn more about the specific genes and DNA changes in these DNA stretches that could be causing ovarian cancer," but she says the newly implicated regions of the genome also contain some familiar suspects.

"Common genetic 'typos' at 8q24 have already been shown to render some people vulnerable to prostate, colorectal, breast and bladder cancers, so it's not too surprising that there may be something there related to ovarian cancer," Goode said. "What is surprising is that we found that three of the most common SNPs for ovarian cancer lie quite a distance away from this bunch of troublemakers – in an apparent gene desert – which suggests they may be causing functional problems by a very different mechanism."