Reassessment of casual association between body mass index and site-specific solid cancers: A comprehensive Mendelian randomization study

Abstract

Abstract Purpose Previous Mendelian randomization (MR) studies on association between body mass index (BMI) and cancer only focused on several common cancers, and the genetic instruments varied, making the effect of BMI on other cancers unclear and direct comparison across all cancer types difficult. Our comprehensive MR aims to reinforce the established evidence of the association. Methods We conducted a unified MR analysis to reassess the association between BMI and 19 site-specific solid cancers. Genetic instruments for BMI were extracted from genome-wide association studies (GWAS) of 806,834 European individuals and 86,757 East Asian individuals, respectively. The associations of genetic instruments with 19 site-specific solid cancer (sub)types extracted from the FinnGen study, the Biobank Japan (BBJ) project, and international consortia were examined by using various MR methods. Results For lung, endometrial and breast cancers in the FinnGen study, estimation of the MR analysis aids the triangulation of the positive or inverse association between genetically predicted BMI and these (sub)types. In several large consortia in the European population, our results strengthen confidence in previously established positive findings for lung, ovarian, endometrial and breast cancer and null findings for prostate cancer. In the BBJ project, no causal association was found between BMI and cancers, although a possible increased risk for endometrial cancer may exist. Conclusion Our comprehensive MR estimates reinforce the causal role of BMI in some solid cancers in the European population but cannot rule out a possible causal role in some other cancer (sub)types and in other populations.