Circulating vitamin C and digestive system cancers: Mendelian randomization study

Clin Nutr. 2022 Sep;41(9):2031-2035. doi: 10.1016/j.clnu.2022.07.040. Epub 2022 Aug 7.


Background & aims: Vitamin C is an antioxidant with a potential role in the prevention of digestive system cancers, but there is yet no consensus whether vitamin C has a causal role in these cancers. The aim of this study was to utilize Mendelian randomization to decipher the potential causal associations of vitamin C with risk of digestive system cancers.

Methods: Ten genetic variants previously found to be significantly associated with circulating vitamin C were used as instrumental variables. Effect size estimates for the genetic associations of the vitamin C-associated genetic variants with six major malignancies of digestive system were obtained from the FinnGen (N = 309 154) and UK Biobank (N = 367 542) studies. Results from the two studies were combined using meta-analysis.

Results: Genetically predicted higher circulating vitamin C showed a suggestive association with lower risk of small intestine and colorectal cancer after accounting for multiple testing. The odds ratio per 1 standard deviation increment in circulating vitamin C was 0.55 (95% confidence interval 0.32-0.94; P = 0.029) for small intestine cancer and 0.84 (95% confidence interval 0.73-0.96; P = 0.013) for colorectal cancer. There was a suggestive association between genetically predicted higher circulating vitamin C with lower risk of liver cancer in FinnGen but no association in the meta-analysis (odds ratio 0.69; 95% CI 0.36-1.32; P = 0.265). Genetically predicted circulating vitamin C was not associated with cancers of the esophagus, stomach, or pancreas.

Conclusion: This Mendelian randomization study indicates that vitamin C might play a role in the prevention of small intestine and colorectal cancer.

Keywords: Ascorbic acid; Cancer; Digestive system; Mendelian randomization; Nutrients; Vitamin C.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ascorbic Acid
  • Colorectal Neoplasms*
  • Digestive System Neoplasms* / epidemiology
  • Digestive System Neoplasms* / genetics
  • Humans
  • Mendelian Randomization Analysis / methods
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Vitamins


  • Vitamins
  • Ascorbic Acid