Causal effects of one-carbon metabolism molecules on cancers risk: a Mendelian randomization study.

Background: An association between the one-carbon metabolism molecules, such as vitamin B6 (VB6), vitamin B12 (VB12), folate and homocysteine (Hcy), and the incidence of various cancers risk has been reported in observational studies, but the causal relationship between one-carbon metabolism molecules and various cancers risk remains unclear. Our aim was to assess the causal effect of one-carbon metabolism molecules on various cancers risk using a two-sample Mendelian randomization (MR) approach.

Methods: We performed two-sample MR to analyze associations between four one-carbon metabolism molecules and seven cancers in Europeans. Methods included IVW, weighted median, MR-Egger, MR-PRESSO, and outlier tests.

Results: Hcy: Suggestive causal association with reduced GC risk (OR = 0.5427; P = .0217) and increased KC risk (OR = 1.3744; P = .0465). High Hcy levels linked to higher PCA (OR = 1.1038; P = .0496) and KC risk (OR = 1.5444; P = .0430), but lower GC risk (OR = 0.6487; P = .0499).Folate: Higher levels associated with increased CRC risk (OR = 1.2945; P = .0346) and reduced PCA risk (OR = 0.8330; P = .0486).VB12: Suggestive causal association with reduced BC (OR = 0.7421; P = .0203) and GC risk (OR = 0.4812; P = .0267). The causal associations of the above combinations were robust through the test of heterogeneity and pleiotropy.

Conclusions: The large MR analysis indicated that one-carbon metabolism molecules may be causally associated with various cancers risk.