Abstract
The current state of knowledge on the relationship between lifestyle factors, glycemic traits, lipoprotein traits with liver cancer risk is still uncertain despite some attempts made by observational studies. This study aims to investigate the causal genetic relationship between factors highly associated with liver cancer incidence by using Mendelian randomization (MR) analysis. Employing MR analysis, this study utilized previously published GWAS datasets to investigate whether lifestyle factors, glycemic traits, and lipoprotein traits would affect the risk of liver cancer. The study utilized three MR methods, including inverse variance-weighted model (IVW), MR Egger, and weighted median. Furthermore, MR-Egger analyses were performed to detect heterogeneity in the MR results. The study also conducted a leave-one-out analysis to assess the potential influence of individual SNPs on the MR analysis results. MR-PRESSO was used to identify and remove SNP outliers associated with liver cancer. MR analyses revealed that 2-h glucose (odds ratio, OR 2.33, 95% confidence interval, CI 1.28-4.21), type 2 diabetes mellitus (T2DM, OR 1.67, 95% CI 1.18-2.37), body mass index (BMI, OR 1.67, 95% CI 1.18-2.37), waist circumference (OR 1.78, 95% CI 1.18-2.37) were associated with increased risk of liver cancer. On the contrary, apolipoproteins B (APOB, OR 0.67, 95% CI 0.47-0.97), and low-density lipoprotein (LDL, OR 0.62, 95% CI 0.42-0.92) were negatively related to liver cancer risk. Additionally, after adjusting for BMI, apolipoproteins A-I (APOA-I, OR 0.56, 95% CI, 0.38-0.81), total cholesterol (TC, OR 0.72, 95% CI, 0.54-0.94), and total triglycerides (TG, OR 0.57, 95% CI, 0.40-0.78) exhibited a significant inverse correlation with the risk of liver cancer. This study supports a causal relationship between 2-h glucose, T2DM, BMI, and waist circumference with the increased risk of liver cancer. Conversely, the study reveals a cause-effect relationship between TC, TG, LDL, APOA-I, and APOB with a decreased risk of liver cancer.