Discovery of Five New Genomic Risk Factors for Uterine Cancer

Recent research has unveiled five novel genomic risk factors associated with endometrial cancer, a prevalent form of gynecological cancer affecting approximately 400,000 women globally each year. This breakthrough study, spearheaded by the Department of Obstetrics and Gynecology at Hannover Medical School (MHH), analyzed genetic data from various national biobanks to identify specific genetic changes that may contribute to the development of tumors in the uterine lining.

Endometrial cancer, characterized by cancerous growth in the uterus lining, accounts for about 100,000 deaths annually. While factors such as obesity, diabetes, and elevated estrogen levels are known contributors to the disease, a genetic predisposition plays a role in roughly 5% of cases. This genetic susceptibility is often linked to hereditary syndromes, including Lynch syndrome and Cowden syndrome. However, many genetic causes remain unidentified.

The collaborative research initiative involved the examination of genetic data from over 17,000 endometrial cancer patients and 290,000 healthy control subjects. The findings, which have been published in the journal eBioMedicine, highlight five new genomic loci likely associated with increased risk for endometrial cancer.

One significant focus of the investigation was a gene known as Navigator-3 (NAV3). Experiments revealed that deactivation of NAV3 led to accelerated growth of uterine cells, while excessive activity resulted in cell death. These observations suggest that NAV3 functions as a tumor suppressor gene, typically limiting cell proliferation in the endometrium and thereby inhibiting cancer development. Notably, levels of NAV3 were found to be significantly reduced in endometrial carcinoma cases.

With this latest discovery, the total number of recognized genomic risk factors for endometrial cancer has risen from 16 to 21. Researchers assert that this expanded knowledge enhances the ability to predict hereditary risk factors associated with uterine cancer more accurately. Understanding the genetic underpinnings of this disease not only facilitates more precise risk assessments for women but also identifies potential targets for preventive strategies and innovative therapeutic approaches.

The insights gained from this study underscore the importance of ongoing research into the genetic basis of cancer. As noted by the director of the MHH Women's Clinic, foundational research is crucial for the development of future cancer therapies. The identification of NAV3 as a promising candidate for further investigation marks a significant step towards understanding the molecular mechanisms of endometrial cancer.