Uncommon genetic variations may contribute to ovarian cancer risk

"We are trying to identify new 'spelling mistakes,' or variants in the genetic code, that may influence a woman's risk for ovarian cancer," said co- investigator Jenny Permuth Wey, PhD, an applied research scientist in the Department of Cancer Epidemiology at Moffitt Cancer Center. "We are particularly interested in genetic variants that are not common in the population (those carried by less than 1 and 20 women) because uncommon variants are not well studied and evidence suggests they may significantly contribute to cancer risk."

This is the largest study of its kind to use new technology to comprehensively investigate the inherited basis of ovarian cancer. To capture uncommon genetic variants, the study used an exome genotyping array to genotype 7,060 epithelial ovarian cancer (EOC) cases and 6,712 cancer-free women from the Ovarian Cancer Association Consortium. Preliminary data from this large-scale study revealed novel variants that may influence susceptibility to EOC.

"Ovarian cancer is the leading cause of death from gynecologic malignancy, and it is typically diagnosed at an advanced stage with little chance for cure," said Jennifer A. Doherty, PhD, a member of the Dartmouth-Hitchcock Norris Cotton Cancer Center and a co-author of the study. "This collaborative effort including 19 studies from the international Ovarian Cancer Association Consortium provides clues that will lead to a better understanding of how and why ovarian cancer develops, and may also inform targeted treatment, prevention and screening strategies."

The researchers acknowledge the Ovarian Cancer Association Consortium and the Genetic Associations and Mechanisms in Oncology (GAME-ON): a National Cancer Institute Post-Genome Wide Association Study Initiative (U19-CA148112).