We conducted a two-sample Mendelian randomization analysis to assess the causal effects of
NAFLD on 22 extrahepatic
cancers. We examined the association of
NAFLD with extrahepatic
cancers using multiple methods in the largest genome-wide association study meta-analysis to date. We also replicated the analyses and performed two independent sensitivity analysis in the largest genome-wide association study of UK Biobank.
RESULTS: Using the weighted median method, genetically predicted
NAFLD was significantly associated with female
breast cancer risk (odds ratio [OR] 15.99; 95% confidence interval [CI] 9.58-26.69). Genetically predicted
NAFLD is associated with cervical and
laryngeal cancers using the inverse variance weighting method, and the
ORs were 2.44 (95% CI 1.43-4.14) and 1.94 (95% CI 1.35-2.78), respectively. We observed that patatin-like
phospholipase domain-containing
protein 3-driven and transmembrane 6 superfamily member 2-driven
NAFLD were associated with increased risks of
leukemia,
lung cancer, and
prostate cancers (all with p < 0.05). Furthermore, we confirmed the causal association between
NAFLD and
breast cancer using five known single-nucleotide polymorphisms of
NAFLD and six genome-wide association study-identified variants. The
ORs of the weighted median estimator was 10.76 (95% CI 8.27-13.98) and 10.76 (95% CI 8.25-14.04), respectively (p < 0.001).
CONCLUSION: