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Cancer Epidemiol Biomarkers Prev. 2018 Oct 19. pii: cebp.1198.2018. doi: 10.1158/1055-9965.EPI-17-1198. [Epub ahead of print]

Folic acid and vitamin-B12 supplementation and the risk of cancer: long-term follow-up of the B-vitamins for the Prevention Of Osteoporotic Fractures (B-PROOF) trial.

Author information

1
Intern Medicine, Erasmus University Medical Center.
2
Epidemiology, Erasmus Medical Center j.c.kiefte-dejong@erasmusmc.nl.
3
Internal Medicine, Erasmus University Medical Center.
4
Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam.
5
Department of Medical Oncology, Academic Medical Center.
6
Human Nutrition and Health, Wageningen University.
7
Research, Comprehensive Cancer Organisation.
8
Epidemiology & Biostatistics, Erasmus Medical Center.
9
Department of Internal Medicine, Erasmus Medical Center.
10
Internal Medicine/Section of Geriatric Medicine, Department of Internal Medicine, Amsterdam Public Health Research Institute, Erasmus University Medical Center/Amsterdam UMC, (University) of Amsterdam.

Abstract

BACKGROUND:

Folic acid and vitamin-B12 play key roles in one-carbon metabolism. Disruption of one-carbon metabolism may be involved in the risk of cancer. Our aim was to assess the long-term effect of supplementation with both folic acid and vitamin-B12 on the incidence of overall cancer and on colorectal cancer in the B-PROOF trial.

METHODS:

Long-term follow-up of B-PROOF trial participants (N=2,524), a multi-center, double-blind randomized placebo-controlled trial designed to assess the effect of 2-3 years daily supplementation with folic acid (400 µg) and vitamin-B12 (500 µg) versus placebo on fracture incidence. Information on cancer incidence was obtained from the Netherlands cancer registry (Integraal Kankercentrum Nederland), using the International Statistical Classification of Disease (ICD-10) codes C00-C97 for all cancers (except C44 for skin cancer), and C18-C20 for CRC.

RESULTS:

Allocation to B-vitamins was associated with a higher risk of overall cancer (171 [13.6%] vs. 143 [11.3%]), HR 1.25; 95%CI 1.00-1.53, p=0.05). B-vitamins were significantly associated with a higher risk of colorectal cancer (43[3.4%] vs. 25[2.0%]), HR 1.77; 95%CI 1.08-2.90, p=0.02).

CONCLUSION:

Folic acid and vitamin-B12 supplementation was associated with an increased risk of colorectal cancer.

IMPACT:

Our findings suggest that folic acid and vitamin-B12 supplementation may increase the risk of colorectal cancer. Further confirmation in larger studies and in meta-analyses combining both folic acid and vitamin-B12 are needed to evaluate whether folic acid and vitamin B12 supplementation should be limited to patients with a known indication such as a proven deficiency.

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