Genetically predicted circulating B vitamins in relation to digestive system cancers

Shuai Yuan, Siddhartha Kar, Susanna Larsson*, et al.

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Background Folate, vitamin B6 and vitamin B12 have been associated with digestive system cancers. We conducted a two-sample Mendelian randomisation study to assess the causality of these associations. Methods Two, one and 14 independent single nucleotide polymorphisms associated with serum folate, vitamin B6 and vitamin B12 at the genome-wide significance threshold were selected as genetic instruments. Summary-level data for the associations of the vitamin-associated genetic variants with cancer were obtained from the UK Biobank study including 367,561 individuals and FinnGen consortium comprising up to 176,899 participants. Results Genetically predicted folate and vitamin B6 concentrations were not associated with overall cancer, overall digestive system cancer or oesophageal, gastric, colorectal or pancreatic cancer. Genetically predicted vitamin B12 concentrations were positively associated with overall digestive system cancer (ORSD, 1.12; 95% CI 1.04, 1.21, p = 0.003) and colorectal cancer (ORSD 1.16; 95% CI 1.06, 1.26, p = 0.001) in UK Biobank. Results for colorectal cancer were consistent in FinnGen and the combined ORSD was 1.16 (95% CI 1.08, 1.25, p < 0.001). There was no association of genetically predicted vitamin B12 with any other site-specific digestive system cancers or overall cancer. Conclusions These results provide evidence to suggest that elevated serum vitamin B12 concentrations are associated with colorectal cancer.
Original languageEnglish
Number of pages7
JournalBritish Journal of Cancer
Early online date9 Apr 2021
Publication statusPublished - 9 Apr 2021


  • Cancer genetics
  • Gastrointestinal cancer
  • Predictive markers

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