Abstract
INTRODUCTION: Vitamin intake may reduce gastrointestinal cancer risk, but how genetic polymorphisms in vitamin metabolism affect this association remains unclarified. This meta-analysis examined whether genetic polymorphisms in vitamin metabolism influence the association between dietary and circulating vitamins and the risk of gastrointestinal cancers. METHODS: Literature search was conducted to gather studies investigating the associations between vitamins, genetic polymorphisms, and gastrointestinal cancer risk. Statistical analyses were conducted using "meta" package in R. RESULTS: Our meta-analysis incorporated 64 studies on colorectal cancer (CRC), gastric cancer, and esophageal cancer, focusing on vitamin B and vitamin D. High dietary intake of vitamin B was significantly associated with reduced gastrointestinal cancer risk (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.79-0.90), as was its circulating level (OR 0.53, 95% CI 0.36-0.78). Individuals harboring the MTHFR 1298 AA/AC and CC genotypes demonstrated varying association of CRC risk with dietary vitamin B intake ( P -het = 0.04), whereas the significant inverse association of circulating vitamin B with CRC risk was found only for MTHFR 677 TT carriers (OR 0.57, 95% CI 0.33-0.97), but not for the CC/CT genotype (OR 0.98, 95% CI 0.80-1.21, P -het = 0.06). High dietary (OR 0.69, 95% CI 0.53-0.90) and circulating vitamin D levels (OR 0.74, 95% CI 0.59-0.94) significantly lowered gastrointestinal cancer risk. The inverse association between circulating vitamin D and CRC risk was exclusively yielded for VDR TaqI Tt/tt carriers (OR 0.52, 95% CI 0.28-0.95), other than the TT genotype (OR 0.91, 95% CI 0.70-1.19, P -het = 0.10). DISCUSSION: High dietary and circulating vitamin B and vitamin D levels were associated with lowered gastrointestinal cancer risk, and the associations may be modified by certain genetic variations in vitamin metabolism pathways.