International Consortium Identifies Multiple Genes Associated With Ovarian Cancer Risk
Cedars-Sinai Investigators, International Team Confirm 27 Ovarian Cancer Risk Regions
A collaborative group of Cedars-Sinai investigators, alongside an international team of researchers known as the Ovarian Cancer Association Consortium, has identified five previously unidentified regions of the genome—the body’s hub of genetic makeup—and confirmed 22 other known regions associated with the risk of developing ovarian cancer.
The findings were recently published in the American Journal of Human Genetics.
In total, investigators used data from more than 26,000 women with ovarian cancer and 100,000 women without the disease. Investigators then confirmed 27 risk regions—meaning areas within an individual’s genetic makeup—that could make women more susceptible to developing ovarian cancer.
“The big takeaway is that multiple genetic variants are associated with the risk of ovarian cancer, but the risks of each variant are small,” said Paul Pharoah, MD, PhD, professor and research scientist in the Department of Computational Biomedicine at Cedar-Sinai, and corresponding author of the study.
How to decipher this risk, however, comes down to genetics.
“We used a variety of bioinformatic approaches to identify multiple genes that are likely to be important in the biology of ovarian cancer risk,” Pharoah said.
The findings provide a framework for improving disease prediction and prevention, according to Pharoah and Michelle Jones, PhD, a study author and assistant professor and co-director of the Applied Genomics, Computation and Translation Core in the Department of Biomedical Sciences.
“In this study we have continued to learn more about how differences in our DNA sequence change the way our genes are expressed in a way that may lead to the development of cancer,” Jones said. “It took a large team of diverse scientists working together to make this project a success, with each bringing unique expertise to the challenge.”
As a next step, the Ovarian Cancer Association Consortium is analyzing how best to combine the risk information from multiple-risk genetic variants.
“We are particularly interested in optimizing polygenic risk models in women from diverse ancestries, which have the potential utility to identify women at high risk of ovarian cancer who may benefit from preventive interventions,” Pharoah said.
Other Cedars-Sinai investigators involved in the study include Simon G. Coetzee, Dennis Hazelett, Pei-Chen Peng and Marc T. Goodman.
The analyses presented in this manuscript have been funded in part by NIH/NCI grants: R01CA207456, R01CA204954, R01CA211707, R01CA211575, R01CA207456, R21CA220078, R00CA256519 and U19C8804/A7058. A proportion of funding was provided as part of an Institutional commitment to The Center for Bioinformatics and Functional Genomics at Cedars-Sinai Medical Center.
Read more from the Cedars-Sinai Newsroom: Cancer Epidemiologist Sees Collaboration As Key to Research Success