Modifiable risk factors and risk of colorectal and endometrial cancer in Lynch syndrome: A systematic review and meta-analysis.

Abstract

e22544 Background: Lynch syndrome is the most common hereditary cause of colorectal and endometrial cancer. Non-genetic risk factors, including obesity, physical activity, alcohol intake, and smoking are well-established in sporadic cancers but are less studied in Lynch syndrome. A better understanding of these risk factors could directly contribute to cancer prevention. Methods: Searches were conducted on MEDLINE, Embase and Web of Science for retrospective or prospective cohort studies that investigated the association between modifiable risk factors and the risk of colorectal or endometrial cancer in people with Lynch syndrome. Screening, data extraction and quality assessment were completed by 2 reviewers independently. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for colorectal and endometrial cancer were pooled using a random effects model. The protocol was prospectively registered on PROSPERO (CRD 42022378462) and the meta-analysis conducted in accordance with PRISMA and MOOSE reporting guidelines. Results: A total of 770 citations were reviewed. Twelve cohort studies involving 12685 patients with Lynch syndrome investigated risk of colorectal cancer, while 3 studies including 1865 patients assessed risk factors for endometrial cancer. Eight colorectal cancer studies were eligible for meta-analysis. Obesity (HR 2.38, 95% CI 1.52-3.73) and alcohol intake (HR 1.43, 95% CI 1.05-1.94) increased colorectal cancer risk, physical activity was protective (HR 0.66, 95% CI 0.52-0.83), and smoking had no effect (HR 1.02 95% CI 0.83-1.27). Type 2 diabetes mellitus and low dietary intake of calcium and multivitamins might increase risk of colorectal cancer, although more studies are needed. There is a paucity of data pertaining to endometrial cancer. In a qualitative synthesis of 3 endometrial cancer cohort studies, female hormonal risk factors and type 2 diabetes mellitus may affect the risk of endometrial cancer, but obesity was not associated with an increased risk. Conclusions: Lifestyle recommendations related to weight, physical activity, and alcohol may also be relevant to cancer prevention for individuals with Lynch syndrome and may provide a meaningful adjunct to standard interventions for risk modification. There are very poor data examining modifiable risk factors in endometrial cancer. Further high-quality prospective cohort studies, in particular including endometrial cancer as an endpoint, are needed to inform evidence-based cancer prevention strategies in this high-risk population.