Scientists Double Number of Known Genetic Risk Factors for Endometrial Cancer

The strength of genome-wide association studies (GWAS) lies in their ability to identify new disease biomarkers through large-scale genomic comparisons of afflicted individuals and unaffected controls. Now, using this powerful technique, an international collaboration of researchers has identified five new gene regions that increase a woman's risk of developing endometrial cancer, one of the most common cancers to affect women, taking the number of known gene regions associated with the disease to nine.

Endometrial cancer affects the uterus lining, typically presenting as an adenocarcinoma. Endometrial cancer is the sixth most common cancer in women worldwide. It is the most common cancer of the female reproductive tract in developed countries, with over 320,000 new cases diagnosed in 2012.

Investigators at the University of Cambridge, Oxford University, and QIMR Berghofer Medical Research Institute in Brisbane studied the DNA of over 7000 women with endometrial cancer and 37,000 women without cancer to identify genetic variants that affected a woman's risk of developing the disease.

The findings from this study were published recently in Nature Genetics in an article entitled "Five Endometrial Cancer Risk Loci Identified Through Genome-Wide Association Analysis."

"Our findings help us to paint a clearer picture of the genetic causes of endometrial cancer in women, particularly where there is no strong family history of cancer," explained co-author Deborah Thompson, Ph.D., senior research associate in the Department of Public Health and Primary Care at the University of Cambridge. "Before this study, we only knew four genome regions in which a common genetic variant increases a woman's risk of endometrial cancer."

"In this study, we have identified another five regions, bringing the total to nine," Dr. Thompson continued. "This finding doubles the number of known risk regions, making an important contribution to our knowledge of the genetic drivers of endometrial cancer."

The researchers also looked at how the identified gene regions might increase cancer risk and how these findings could have implications for the future treatment of endometrial cancer patients.

"Interestingly, several of the gene regions we identified in the study were already known to contribute to the risk of other common cancers such as ovarian and prostate," Dr. Thompson remarked. "Although each variant only increases risk by around 10–15%, their real value will be in looking at the total number of such variants inherited by a woman, together with her other risk factors, to identify those women at higher risk of endometrial cancer so that they can be regularly checked and be alert to the early signs and symptoms of the disease."

The researchers are now focusing on how they can turn their data into useful information when deciding clinical treatment courses for patients.

"As we develop a more comprehensive view of the genetic risk factors for endometrial cancer, we can start to work out which genes could potentially be targeted with new treatments down the track," noted senior study author Amanda Spurdle, Ph.D., associate professor and group leader at QIMR Berghofer Medical Research Institute. "In particular, we can start looking into whether there are already approved drugs that can use to target those genes."