Study Finds New Genetic Variants in Ovarian Cancer

A new international study has identified 12 new genetic variants associated with an increased risk of developing epithelial ovarian cancer (EOC).

Investigators report in Nature Genetics that they have identified nine new susceptibility loci for different epithelial ovarian cancer histotypes. Among these 9 loci, they have identified six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2, and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1), and one for endometrioid EOC (5q12.3). OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC, was also identified.

Investigators at the Moffitt Cancer Center analyzed 25,509 EOC cases and 40,941 controls from pooled data from multiple genome-wide genotyping projects. They conducted a meta-analysis of 31,448 BRCA1 and BRCA2 mutation carriers (including 3,887 mutation carriers with EOC) to better understand the association between mutation carriers with EOC and BRCA2 mutation carriers. Using this approach, they found three additional susceptibility loci at 2q13, 8q24.1, and 12q24.31.

The new study is from the OncoArray Consortium, a collaborative effort that includes more than 400 scientists from the United States, United Kingdom, and Australia. Prior to this study, researchers had identified 27 common genetic variants, which account for roughly 4% of inherited risk for the disease.

The current investigation identifies 12 new genetic variants associated with ovarian cancer risk and it confirms 18 previously published variants. In total, there are 30 known generic variants associated with ovarian cancer risk, accounting for 6.5% of the inherited risk.

“We now need to take a closer look at the effect these variants have at the molecular and cellular levels.  If we can understand how they work, we can improve treatment options and work towards the prevention of ovarian cancer,” said Catherine Phelan, MD, PhD, MMS, who is an associate member of the Cancer Epidemiology Program at Moffitt Cancer Center, Tampa, Florida.

Phelan said this study highlights that fact that ovarian cancer is a very complex disease. She also notes that the 30 known risk variants account for just a small fraction of the inherited component and there will likely be many more genetic variants involved.

When a patient is diagnosed and treated in the early stages of ovarian, the 5-year survival rate is over 90%. However, only about 20% of all cases are caught early. It is hoped that it may be possible to pick up cases earlier through a better understanding of the genetic underpinnings of EOC.

Moffitt Cancer Center Director Thomas Sellers, PhD, MPH, said these latest findings are further proof that progress in the prevention and cure of cancer requires collaboration. This may be especially true for ovarian cancer. Sellers noted the current investigation involved pooling more than 60 independent studies from around the world.