Abstract：Objective To examine the causal relationships between obesity, peripheral blood lipid indicators and non-small cell lung cancer (NSCLC) using Mendelian randomization (MR) method, so as to provide the basis for developing NSCLC prevention and control strategies. Methods Genetic variation data of three obesity evaluation indicators, including body mass index (BMI), body fat ratio (BFR) and waist-to-hip ratio (WHR), and seven peripheral blood lipid indicators, including triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and lipoprotein a [LP (a)] were collected through genome-wide association studies (GWAS) and related public databases. Potential causal relationships between obesity, peripheral blood lipid indicators and NSCLC were analyzed using inverse-variance weighted (IVW) method and multivariable MR analysis upon a random effect model. Heterogeneity and horizontal pleiotropy of instrumental variables were evaluated using Cochran's Q test and MR-Egger regression. Results There was statistically association between BMI with NSCLC (OR=1.256, 95%CI: 1.087-1.451); there were no statistically associations between BFR, WHR, seven peripheral blood lipid indicators and NSCLC (all P>0.005). There was heterogeneity in the association between BMI, BFR, WHR, TG, HDL-C and NSCLC (all P<0.05); no horizontal pleiotropy of instrumental variables was found (all P>0.05). There was no statistically association between BMI and NSCLC after adjusting BFR (OR=1.367, 95%CI: 0.878-2.128); there was still statistically association between BMI and NSCLC after adjusting WHR and peripheral blood lipid indicators (both P<0.05). Conclusions The increase of BMI is associated with the increased risk of NSCLC incidence. BFR may be a potential influencing factor for the association between BMI and NSCLC.
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