Causal relationship between Metformin treatment and ovarian cancer on-set risk based on two-sample Mendelian randomization
Objective To investigate Mendelian randomization(MR)analysis of causal relationship between Metformin treatment and ovarian can-cer onset risk.Methods This study was based on two-sample MR analysis,Metformin was used as exposure factor,ovarian cancer as outcome vari-able.Datas for Metformin were derived from the genome wide association study(GWAS)on the IEU OpenGWAS project website and published drug target studies,and GWAS datas for ovarian cancer were derived from the Ovarian Cancer Association Consortium.Five methods were performed for MR analysis,including random-effects inverse variance-weighted(IVW)method,weighted mode method,MR-Egger regression method,weighted median method,and simple mode method;Cochrane Q test was used for heterogeneity test,MR-Egger intercept method and MR-PRESSO method for horizontal pleiotropy test;the leave-one method determined whether a single instrumental variable had an effect on the result.Results For the first exposure factor,45 single nucleotide polymorphisms were obtained as instrumental variables;for the second exposure,32 instrumental vari-ables were obtained.There was no causal relationship between Metformin therapy and ovarian cancer onset risk;for the first exposure factor,there was no heterogeneity and horizontal pleiotropy in the instrumental variables;for the second exposure factor,there was heterogeneity in instrumental variables,but random-effects IVW method was used in this study,which did not affect the final results;and the leave-one method indicated no ab-normal instrumental variables.There wad no causal relationship between Metformin therapy and the different types of ovarian cancer onset risk.For both exposure factors,there were partial heterogeneity in instrumental variables,but random-effects IVW method was used in this study,which did not affect the final results;the leave-one method indicated no abnormal instrumental variables.Conclusion There is no significant causal relation-ship between Metformin treatment and ovarian cancer onset risk.
MetforminMendelian randomizationGenome wide association studyCausal inferenceOvarian cancer
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