Discovery of Five New Genetic Risk Factors for Uterine Cancer

Researchers from Hannover Medical School have identified five new genetic regions associated with an increased risk of developing uterine cancer, also known as endometrial cancer. This significant breakthrough was achieved through an extensive international study analyzing genomic data from biobanks across multiple countries. By comparing the DNA of over 17,000 women diagnosed with endometrial cancer to around 290,000 healthy women, scientists pinpointed specific genetic loci that contribute to tumor development in the uterine lining.

Endometrial cancer is a prevalent gynecological cancer worldwide, with approximately 400,000 new cases and 100,000 deaths annually. Known risk factors include obesity, diabetes, elevated estrogen levels, and advancing age. While hereditary factors account for about 5% of cases—linked to syndromes like Lynch and Cowden—many genetic causes remain unknown.

The team, led by Dr. Thilo Dörk-Bousset, utilized high-throughput genetic techniques to identify five key genomic areas that are strongly linked to endometrial cancer risk. These findings have been published in eBioMedicine and represent a crucial step toward understanding genetic predispositions.

One gene of particular interest is NAV3. Laboratory studies demonstrated that inactivation of NAV3 in uterine tissue leads to accelerated cell growth, while increased activity causes cell death. This suggests NAV3 functions as a tumor suppressor gene, generally reducing the likelihood of cancer formation. Notably, NAV3 levels are substantially lower in endometrial tumors, highlighting its potential role in cancer prevention.

This research increases the number of known genetic risk factors for endometrial cancer from 16 to 21. Identifying these genes enhances our ability to predict individual risk accurately. Moreover, understanding the functions of these genes opens new possibilities for preventive measures and targeted therapies. For example, the regulation of NAV3 is under active investigation as a potential therapeutic target.

Overall, these insights mark a significant advancement in the understanding of uterine cancer genetics, paving the way for improved prediction methods and innovative treatment strategies. The findings emphasize the importance of basic genetic research in developing tomorrow’s cancer therapies.