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

Sadaf Oliai Araghi, Jessica C. Kiefte-De Jong, Suzanne C. Van Dijk, Karin M.A. Swart, Hanneke W. van Laarhoven, Natasja M. van Schoor, Lisette C.P.G.M. de Groot, Valery Lemmens, Bruno H. Stricker, Andre G. Uitterlinden, Nathalie Van Der Velde

Research output: Contribution to journalArticleAcademicpeer-review

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 Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial. Methods: Long-term follow-up of B-PROOF trial participants (N ¼ 2,524), a multicenter, double-blind randomized placebo-controlled trial designed to assess the effect of 2 to 3 years daily supplementation with folic acid (400 mg) and vitamin B12 (500 mg) 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 colorectal cancer. 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% confidence interval (CI), 1.00-1.53, P ¼ 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 ¼ 0.02]. Conclusions: 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.

LanguageEnglish
Pages275-282
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume28
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019

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Vitamin B Complex
Osteoporotic Fractures
Vitamin B 12
Folic Acid
Colorectal Neoplasms
International Classification of Diseases
Neoplasms
Incidence
Carbon
Placebos
Confidence Intervals
Skin Neoplasms
Netherlands
Registries
Meta-Analysis
Randomized Controlled Trials

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Araghi, Sadaf Oliai ; Kiefte-De Jong, Jessica C. ; Van Dijk, Suzanne C. ; Swart, Karin M.A. ; van Laarhoven, Hanneke W. ; van Schoor, Natasja M. ; de Groot, Lisette C.P.G.M. ; Lemmens, Valery ; Stricker, Bruno H. ; Uitterlinden, Andre G. ; Van Der Velde, Nathalie. / 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. In: Cancer Epidemiology Biomarkers and Prevention. 2019 ; Vol. 28, No. 2. pp. 275-282.
@article{07a11e3e68e94d8bbcdb0783ddabd3f8,
title = "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",
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 Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial. Methods: Long-term follow-up of B-PROOF trial participants (N ¼ 2,524), a multicenter, double-blind randomized placebo-controlled trial designed to assess the effect of 2 to 3 years daily supplementation with folic acid (400 mg) and vitamin B12 (500 mg) 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 colorectal cancer. 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{\%} confidence interval (CI), 1.00-1.53, P ¼ 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 ¼ 0.02]. Conclusions: 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.",
author = "Araghi, {Sadaf Oliai} and {Kiefte-De Jong}, {Jessica C.} and {Van Dijk}, {Suzanne C.} and Swart, {Karin M.A.} and {van Laarhoven}, {Hanneke W.} and {van Schoor}, {Natasja M.} and {de Groot}, {Lisette C.P.G.M.} and Valery Lemmens and Stricker, {Bruno H.} and Uitterlinden, {Andre G.} and {Van Der Velde}, Nathalie",
year = "2019",
month = "2",
day = "1",
doi = "10.1158/1055-9965.EPI-17-1198",
language = "English",
volume = "28",
pages = "275--282",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research",
number = "2",

}

Araghi, SO, Kiefte-De Jong, JC, Van Dijk, SC, Swart, KMA, van Laarhoven, HW, van Schoor, NM, de Groot, LCPGM, Lemmens, V, Stricker, BH, Uitterlinden, AG & Van Der Velde, N 2019, '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', Cancer Epidemiology Biomarkers and Prevention, vol. 28, no. 2, pp. 275-282. https://doi.org/10.1158/1055-9965.EPI-17-1198

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. / Araghi, Sadaf Oliai; Kiefte-De Jong, Jessica C.; Van Dijk, Suzanne C.; Swart, Karin M.A.; van Laarhoven, Hanneke W.; van Schoor, Natasja M.; de Groot, Lisette C.P.G.M.; Lemmens, Valery; Stricker, Bruno H.; Uitterlinden, Andre G.; Van Der Velde, Nathalie.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 28, No. 2, 01.02.2019, p. 275-282.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Folic acid and Vitamin B12 supplementation and the risk of cancer

T2 - Cancer Epidemiology Biomarkers and Prevention

AU - Araghi, Sadaf Oliai

AU - Kiefte-De Jong, Jessica C.

AU - Van Dijk, Suzanne C.

AU - Swart, Karin M.A.

AU - van Laarhoven, Hanneke W.

AU - van Schoor, Natasja M.

AU - de Groot, Lisette C.P.G.M.

AU - Lemmens, Valery

AU - Stricker, Bruno H.

AU - Uitterlinden, Andre G.

AU - Van Der Velde, Nathalie

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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 Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial. Methods: Long-term follow-up of B-PROOF trial participants (N ¼ 2,524), a multicenter, double-blind randomized placebo-controlled trial designed to assess the effect of 2 to 3 years daily supplementation with folic acid (400 mg) and vitamin B12 (500 mg) 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 colorectal cancer. 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% confidence interval (CI), 1.00-1.53, P ¼ 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 ¼ 0.02]. Conclusions: 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.

AB - 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 Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial. Methods: Long-term follow-up of B-PROOF trial participants (N ¼ 2,524), a multicenter, double-blind randomized placebo-controlled trial designed to assess the effect of 2 to 3 years daily supplementation with folic acid (400 mg) and vitamin B12 (500 mg) 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 colorectal cancer. 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% confidence interval (CI), 1.00-1.53, P ¼ 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 ¼ 0.02]. Conclusions: 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.

U2 - 10.1158/1055-9965.EPI-17-1198

DO - 10.1158/1055-9965.EPI-17-1198

M3 - Article

VL - 28

SP - 275

EP - 282

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 2

ER -