IARC 60th Anniversary - 19-21 May 2026
Session : 21/05/26 - Posters
One-carbon nutrients and cancers: What do we know from the current evidence on cancers and folate, vitamin B12, and choline
YOO S. 1, MONTAZERI A. 1, AOUN A. 1, BENNETT D. 2, BO Y. 3, CHEN P. 4, COLLINS E. 5, DUTHIE S. 6, JENSEN N. 1, ATIPATSA C. 7, LAI J. 8, LI X. 9, MACFARLANE A. 10, MARTINEZ H. 11, MCNULTY H. 12, MOMOLI F. 1, MOSSEY P. 13, MUNGER R. 14, PARAJULI R. 15, POTVIN KENT M. 1, RUBINI M. 17, SENEKAL M. 18, SIKORA L. 1, STINTZI A. 1, THEODORATOU E. 9, WANG H. 4, YAKTINE A. 16, LITTLE J. 1
1 University of Ottawa, Ottawa, Canada; 2 University of Oxford, Oxford, United Kingdom; 3 Xinxiang Medical University, Xinxiang, China; 4 Shanghai Jiao Tong University, Shanghai, China; 5 University of Western Ontario, London, Canada; 6 Robert Gordon University, Aberdeen, United Kingdom; 7 Mzuzu University, Mzuzu, Malawi; 8 Agency for Science, Technology and Research, Singapore, Singapore; 9 University of Edinburgh, Edinburgh, United Kingdom; 10 Health Canada, Ottawa, Canada; 11 Nutrition International, Ottawa, Canada; 12 Ulster University, Coleraine, United Kingdom; 13 University of Dundee, Dundee, United Kingdom; 14 Utah State University, Logan, United States; 15 University of California, San Diego, United States; 16 National Academies of Sciences, Engineering and Medicine, Washington DC, United States; 17 University of Ferrara, Ferrara, Italy; 18 University of Cape Town, Cape Town, South Africa
Background
The known effects of one-carbon metabolism (OCM) on anemia and neural tube defects have influenced nutritional policy in many countries. The involvement of folate in the synthesis of DNA and RNA, methylation processes, and genomic integrity, with vitamin B12 and choline being cofactors, points to considerable biological potential to affect other outcomes including cancers; however, the evidence is fragmented. There may be dual effects of OCM, with low status contributing to increased risk and high-dose supplementation having adverse effects on carcinogenesis.
Objectives: We aimed to synthesize the evidence examining the relationship between folate, vitamin B12, and choline and cancers, focusing on triangulation of the evidence from various study designs investigating different measures of exposure.
Methods: We conducted two umbrella reviews, each on folate and vitamin B12, and a scoping review on choline. For umbrella reviews, we searched Medline, Embase, CINAHL, the Cochrane Library, and the Database of Abstracts of Reviews of Effects from inception to February 2024 for systematic reviews investigating the associations of folate or vitamin B12 (measured as dietary intake, supplementation, or blood concentrations) with any specific cancer outcome. For the scoping review, MEDLINE, CINAHL, and the Cochrane Central Register of Controlled Trials were searched in May 2025 for research involving humans and published in 2000 and onwards. Screening and data extraction were performed in duplicate. We assessed the risk of bias using AMSTAR-2 and ROBIS and graded the credibility of the evidence in the umbrella reviews.
Results: On folate, we identified 67 syntheses, of which 57 provided meta-analyses. A total of 168 non-overlapping associations (unique exposure–unique outcome–unique setting) were reported across 10 cancer types, 3 system cancers and total cancer. Of these, 15 directional associations (colorectal, esophageal, and total cancers) were assessed to be at a highly suggestive level of credibility; an additional 17 directional and 10 null associations were assessed to be at a suggestive level of credibility. In prostate cancer, we identified signals of positive relationship, although of weak credibility. Over half of the syntheses had a high risk of bias. On vitamin B12, we identified 9 meta-analyses examining 15 non-overlapping associations across 5 cancer types. Of these, 2 directional associations (colorectal, esophageal cancers) and 5 null associations were assessed to be at a suggestive level of credibility. On choline, we found four prospective cohort studies (Europe, US, China) reporting two directional associations (colon cancer, hepatocellular carcinoma mortality) and two null associations.
Conclusion: We identified a highly suggestive level of evidence indicating an inverse relationship between folate status and risk of esophageal, colorectal, childhood brain/spinal tumors and total cancers. The evidence on vitamin B12 was limited; however, considering its interrelationship with folate in OCM, more research is warranted, particularly in the global context of expanding food fortification with folic acid and changing dietary patterns owing to climate change and economic insecurity. A large volume of evidence on choline consisted of animal studies. This review identified gaps in the current knowledge and directions for future research on choline.