Genetically Predicted Modifiable Lifestyle Factors in Relation to
Ovarian Cancer Risk by Histologic Subtypes
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.