Genetic liability for smoking and risk of hepatocellular carcinoma: a two-sample Mendelian randomization study

Abstract

Abstract Objective: Observational studies have yielded conflicting results on the association of smoking with the risk of hepatocellular carcinoma (HCC). This study used Mendelian randomization (MR) design to estimate the causal effect of smoking on the risk of HCC. Methods: We used the two-sample MR framework mainly with inverse-variance weighted (IVW) method to estimate the causal effect of genetic liability for smoking on HCC. Complementary sensitivity analyses were conducted to test the robustness of our results. Genome-wide association studies (GWAS) that were based on predominantly European and East Asian ancestry. The sample sizes of the GWAS used in this study ranged from 197,611 to 468,170 participants. This study retrieved and extracted genetic variants associated with smoking and their corresponding summary-level information in HCC from the respective GWAS. Results: All of the results from IVM, IVW radial, IVW with multiplicative random effects, MR-Egger regression, and the weighted median methods demonstrated that genetically predicted smoking was significantly associated with higher odds of HCC, with odds ratios (ORs) of 2.47 (95%CI, 1.22–5.17; P = 0.017), 2.49 (95%CI, 1.19–4.76; P = 0.008), 2.53 (95%CI, 1.30–4.51; P = 0.005), 3.69 (95%CI, 1.36–6.25; P = 0.035) and 1.93 (95%CI, 1.06–3.94; P = 0.049), respectively. Conclusions: Our study provided potential evidence between genetically predicted smoking and HCC.