Association between dark chocolate consumption and the risk of digestive cancers: a two-sample Mendelian randomization study and analysis of NHANES data

This study examined the potential causal relationship between dark chocolate consumption and digestive system cancers (DSCs) using two-sample Mendelian randomization (MR) and an observational analysis of colorectal cancer (CRC) in NHANES 2009–2010. Genetic instruments from UK Biobank GWAS (ukb-b -16,139) were tested in FinnGen, and 3,721 NHANES participants were analyzed for self-reported chocolate consumption frequency. MR inverse-variance weighted analysis suggested a nominal association with CRC (OR = 2.57; p =0 .019), which was not significant after false-discovery-rate correction (FDR p = 0.095). Sensitivity analyses found no pleiotropy or influential SNPs. NHANES survey-weighted models similarly showed no significant association across consumption categories. Both MR and NHANES results consistently indicate no robust evidence that dark chocolate consumption affects DSC risk, suggesting it should not be recommended for cancer prevention.