Yang Xu

and 7 more

Objective: Lifestyle factors including education, coffee intake, tea consumption, dietary fat intake, obesity, physical activities, smoking and alcohol drinking, sleep duration, and insomnia, have been linked to Ovarian Cancer (OC) in observational studies. We assessed whether the concerning factors are causally associated with the risk of OC by histological subtypes. Design: Mendelian Randomization (MR) study. Setting: Independent genetic instruments associated with thirteen lifestyle behaviors were selected from ten genome-wide association studies. Summary-level data for OC subtypes were obtained from the Ovarian Cancer Association Consortium. Population: Exposures population were including 375,833 to 1,232,091 European individuals, outcomes population were including up to 25,509 cases and 40,941 controls. Methods: Two-sample and multivariable MR study, and multiple complementary sensitivity analyses were conducted. Main Outcome Measures: Histological subtypes of OC. Results: We provided unconfounded genetic evidence of inverse associations of genetically predicted years of education and fat intake with specific OC subtypes, which are independent of BMI. Whereas consumption of coffee or tea was positively associated with endometroid OC, which may be partly mediated by BMI. Although physical activity and sleep characteristics have been reported to be the risk factors for OC, no causal associations were observed in our study. Conclusions: Our study clarified the protective and independent role of high level education and relative fat intake in particularly OC subtypes. We also showed detrimental effects of higher coffee or tea consumption on OC histotypes. Our results may provide insight into the corresponding interventions as lifestyle factors can easily be modified.