Associations between six dietary habits and risk of hepatocellular carcinoma: A Mendelian randomization study

Diet is reported to be associated with hepatocellular carcinoma (HCC), but whether there is a causal relationship remains unclear. This study aimed to explore the potential causal associations between dietary habits and HCC risk using Mendelian randomization in an East Asian population. From the BioBank Japan, we obtained summary-level genome-wide association studies data for the following six dietary habits: ever/never drinker (n = 165,084), alcohol consumption (n = 58,610), coffee consumption (n = 152,634), tea consumption (n = 152,653), milk consumption (n = 152,965), and yoghurt consumption (n = 152,097). We also obtained data on HCC (1866 cases and 195,745 controls). Single-nucleotide polymorphisms (SNPs) that were associated with exposures (p < 5 × 10^-8 ) were selected as instrumental variables (IVs). Five, two, and six SNPs were identified for ever/never drinkers, alcohol consumption, and coffee consumption. One SNP was used for consumption of tea, milk, and yoghurt. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by inverse variance weighted (for an IV with more than one SNP) or Wald ratio (for an IV with one SNP). Ever/never drinkers (OR, 1.11; 95% CI, 1.05-1.18; p < 0.001) and alcohol consumption (OR, 1.57; 95% CI, 1.32-1.86; p < 0.001) were positively associated with HCC risk. Conversely, coffee consumption was inversely related to HCC risk (OR, 0.69; 95% CI, 0.53-0.90; p = 0.007). Similar inverse associations were observed for consumption of tea, milk, and yoghurt, with ORs (95% CIs) of 0.11 (0.05-0.26), 0.18 (0.09-0.34), and 0.18 (0.09-0.34), respectively (all p < 0.001). Conclusion: There are potential causal associations between six dietary habits and HCC risk. Our findings inform clinical practice by providing evidence on the impact of dietary habits on HCC.