Dietary and circulating vitamins, polymorphisms of vitamin metabolism genes, and the risk of gastrointestinal cancers: a systematic review and meta-analysis

Objectives: Vitamin intake may reduce gastrointestinal cancer risk, but how vitamin metabolism genetic polymorphisms affect this association remains unclarified. This meta-analysis examined whether vitamin metabolism genetic polymorphisms influence the association between dietary and circulating vitamins and 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 1298AA/AC and CC genotypes demonstrated varying association of CRC risk with dietary vitamin B intake ( P -het=0.04), while the significant inverse association of circulating vitamin B with CRC risk was found only for MTHFR 677TT 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). Conclusion: 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.