Improving the prediction of endometrial cancer risk using genetics
Worldwide Cancer Research
QIMR Berghofer Medical Research Institute
Endometrial cancer (cancer of the uterine lining) is the most commonly diagnosed gynaecological cancer in developed countries, including Australia. Its incidence is rapidly increasing due to the ageing population and rising rates of obesity, the strongest known risk factor for endometrial cancer. This is a global problem, with a recent study reporting increased incidence rates of endometrial cancer in 26 of 43 countries studied. Unlike many cancer types, endometrial cancer-specific mortality has increased approximately 2% each year since 2008, in part due to its increased incidence.   Whilst the link between obesity and endometrial cancer risk is well-recognised, the mechanism for how this occurs is unknown. Understanding which characteristics of obesity are responsible for this relationship would provide vital information not only for informing endometrial cancer risk but also understanding the biology of this disease. How to use the information from obesity and other risk factors effectively to identify women at very high risk of endometrial cancer is not available. Harnessing these data would provide avenues for personalised risk prediction and targeted prevention interventions, including bariatric surgery.   Our research team leads the world’s largest genetic study of endometrial cancer through co-ordination of the Endometrial Cancer Association Consortium and identifying several genetic variants associated with endometrial cancer risk by genome-wide association study. We will use these genetic data to explore the relationship between endometrial cancer and specific obesity-related traits. We will construct endometrial cancer genetic risk scores, integrating genetic data from endometrial cancer risk factors to improve predictive capacity. Finally, we will assess the effect of intervention strategies on reducing endometrial cancer risk, providing essential data for clinical implementation of genetic risk scores for endometrial cancer prevention.
2.1 Biological and endogenous factors