Body shape, fat distribution and sarcopenia and risk of liver cancer in European population: a Mendelian randomization study

Background Body shape, fat and muscle are likely associated with risk of liver cancer. Evidence for the impact of these factor is limited and controversial. Because conventional observational studies cannot sidestep the effect of confounding and reverse causality, it remains unclear whether there is a causal relationship of body shape, composition and its distribution with risk of liver cancer. Methods In this study, a two-sample Mendelian randomization (MR) approach was applied to evaluate the potential causal association of 17 risk factors of body shape, fat distribution and sarcopenia with risk of liver cancer in European population. Summary genetic association estimates for 17 exposures and liver cancer were obtained from MRCIEU GWAS database. Results MR analysis indicated that genetically predicted body mass index (BMI) and waist-to-hip ratio (WHR) were associated with liver cancer risk [OR: 1.0005, P  = 0.037; OR: 1.0014, P  = 0.004, respectively]. Whole body fat mass, trunk fat mass, arm fat mass and leg fat mass were associated with liver cancer risk, while the corresponding fat-free mass were not associated with liver cancer risk. Genetically determined sarcopenia was not associated with liver cancer risk, as either. There did not suggest evidence of potential heterogeneity or directional pleiotropy. Conclusion Our study found genetically predicted BMI, WHR and fat mass were associated with liver cancer risk, and the positive association between fat mass and liver cancer risk did not change with changes in fat distribution. However, fat-free mass and sarcopenia associated factors were not associated with liver cancer risk.