Insight into the causality between basal metabolic rate and endometrial and ovarian cancers: Analysis utilizing systematic Mendelian randomization and genetic association data from over 331,000 UK biobank participants

Background: Observational studies have demonstrated that basal metabolic rate (BMR) is associated with the risk of endometrial cancer (EC) and ovarian cancer (OC). However, it is unclear whether these associations reflect a causal relationship.

Objective: To reveal the causality between BMR and EC and OC, we performed the first comprehensive two-sample Mendelian randomization (MR) analyses.

Methods: Genetic variants were used as proxies of BMR. GWAS summary statistics of BMR, EC and OC were obtained from the UK Biobank Consortium, Endometrial Cancer Association Consortium and Ovarian Cancer Association Consortium respectively. The inverse variance weighted method was employed as the main approach for MR analysis. A series of sensitivity analyses were implemented to validate the robustness and reliability of the results.

Results: BMR was significantly related to an increased risk of EC (OR_SD = 1.49; 95% CI: 1.29-1.72; p-Value < .001) and OC (OR_SD = 1.21; 95% CI: 1.08-1.35; p-Value < .001). Furthermore, the stratified analysis indicated that BMR was positively associated with endometrioid endometrial cancer (EEC) (OR_SD = 1.45; 95% CI, 1.23-1.70; p-Value < .001), clear cell ovarian cancer(CCOC) (OR_SD = 1.89; 95% CI:1.35-2.64; p-Value < .001) and endometrioid ovarian cancer risk (EOC) (OR_SD = 1.45; 95% CI: 1.12-1.88; p-Value = .005). However, there were no significant associations of BMR with invasive mucinous ovarian cancer (IMOC), high-grade serous ovarian cancer (HGSOC) and low-grade serous ovarian cancer (LGSOC). The robustness of the above results was further verified in sensitivity analyses.

Conclusion: The MR study provided etiological evidence for the positive association of BMR with the risk of EC, EEC, OC, CCOC and EOC. But this study did not provide enough evidence suggesting the causal associations of BMR with IMOC, HGSOC and LGSOC.