AUTHOR=Chen Hanxiao , Du Ze , Zhang Yaoyao , Li Mengling , Gao Rui , Qin Lang , Wang Hongjing TITLE=The Association Between Vitamin C and Cancer: A Two-Sample Mendelian Randomization Study JOURNAL=Frontiers in Genetics VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.868408 DOI=10.3389/fgene.2022.868408 ISSN=1664-8021 ABSTRACT=In recent years, many studies have indicated that vitamin C might be negatively associated with the risk of cancer, but the actual relationship between vitamin C and cancer remains ambivalent. Therefore, we utilized a two-sample Mendelian randomization (MR) study to explore the causal associations of genetically predicted vitamin C with the risk of a variety of cancer. Single nucleotide polymorphisms (SNPs) associated with vitamin C at significance level of P < 5×10-8 and with low level of linkage disequilibrium (LD) (r2 < 0.01) were selected from a genome-wide association study (GWAS) meta-analysis of plasms concentration of vitamin C consisting of 52,018 individuals. GWAS outcome data were obtained from UK Biobank, FinnGen Biobank, and the datasets of corresponding consortia. In inverse-variance weight (IVW) method, our results did not support the causal association of genetically vitamin C with the risk of overall cancer and fourteen specific types of cancer types. Similar results were observed in sensitivity analyses where the weighted median and MR-Egger methods were adopted, and heterogeneity and pleiotropy were not observed in statistical models. Therefore, our study suggested that vitamin C was not causally associated with the risk of cancer. Further studies are warranted to discover the potential protective and therapeutic effect of vitamin C on cancer, as well as its underlying mechanisms.