Folate and global health umbrella review series, part 2: syntheses on cancers

Samantha Yoo; Azita Montazeri; Derrick Bennett; Yacong Bo; Peizhan Chen; Susan Duthie; Natalie Jensen; Atipatsa Kaminga; Jun-Shi Lai; Xue Li; Amanda J MacFarlane; Homero Martinez; Helene McNulty; Franco Momoli; Peter Mossey; Patrick Mullie; Ron Munger; Rajendra Prasad Parajuli; Monique Potvin Kent; Michele Rubini; Marjanne Senekal; Lindsey Sikora; Alain Stintzi; Evropi Theodoratou; Hui Wang; Chittaranjan Yajnik; Ann Yaktine; Julian Little

doi:10.7189/jogh.16.04102

Folate and global health umbrella review series, part 2: syntheses on cancers

Samantha Yoo
, Azita Montazeri
, Derrick Bennett
, Yacong Bo
, Peizhan Chen
, Susan Duthie
, Natalie Jensen
, Atipatsa Kaminga
, Jun-Shi Lai
, Xue Li
, Amanda J MacFarlane
, Homero Martinez
, Helene McNulty
, Franco Momoli
, Peter Mossey
, Patrick Mullie
, Ron Munger
, Rajendra Prasad Parajuli
, Monique Potvin Kent
, Michele Rubini

Marjanne Senekal, Lindsey Sikora, Alain Stintzi, Evropi Theodoratou, Hui Wang, Chittaranjan Yajnik, Ann Yaktine, Julian Little

Research output: Contribution to journal › Article › peer-review

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Abstract

Background
Folate has been examined extensively in relation to carcinogenesis due to its role in one-carbon metabolism impacting the synthesis of DNA and RNA, methylation processes, and genomic integrity. Current evidence on the relationship between folate status and the risk of cancer is equivocal: low or deficient folate status may contribute to an increased risk of cancers, while high-dose folic acid supplementation may have adverse effects on carcinogenesis.

Methods
We searched MEDLINE, Embase, CINAHL, the Cochrane Library, and the Database of Abstracts of Reviews of Effects up to February 2024 for systematic reviews and meta-analyses investigating the associations of folate (measured as dietary intake, supplementation, or blood concentrations) with any specific cancer outcome. Screening, data extraction, and risk of bias assessment were performed in duplicate. We assessed the credibility of the evidence using predefined criteria.

Results
We found 67 syntheses, of which 57 provided meta-analyses. Over half of the syntheses had a high risk of bias. We identified 168 unique associations (unique exposure - unique outcome - unique setting) across 10 cancer types, 3 system cancers, and total cancer. Of these, we assessed 15 directional associations (colorectal, oesophageal, and total cancers) to be at a highly suggestive level of credibility, and 17 directional and 10 null associations to be at a suggestive level of credibility.

Conclusions
The available evidence for each category of unique association was generally limited. Highly suggestive associations were found for oesophageal, colorectal, childhood brain and spinal tumours and total cancers. More robust primary studies are warranted to follow-up the signal of a positive relationship reported for prostate cancer warranting further research. Evidence was weak for all but colorectal and oesophageal cancers, or the central nervous system cancers in children.

Registration PROSPERO: CRD42021265041.

Original language	English
Article number	4102
Pages (from-to)	1-19
Number of pages	19
Journal	Journal of Global Health
Volume	16
Early online date	20 Feb 2026
DOIs	https://doi.org/10.7189/jogh.16.04102
Publication status	Published online - 20 Feb 2026

Bibliographical note

Data Availability Statement

The data supporting the findings of this study are available within the article and its supplementary materials.

Funding

This study was funded by Canadian Institutes for Health Research (CIHR) Grant FRN-PJT-175263. The funder had no direct or indirect involvement in the design of the review, data abstraction, synthesis, writing of the report and decision to submit the manuscript for publication.

Funders	Funder number
Public Health Agency of Canada
Canadian Institutes of Health Research	FRN-PJT-175263

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Humans
Neoplasms
Folic Acid
Dietary Supplements
Global Health
Systematic Reviews as Topic
Folic Acid/administration & dosage
Neoplasms/epidemiology

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Cite this

Yoo, S., Montazeri, A., Bennett, D., Bo, Y., Chen, P., Duthie, S., Jensen, N., Kaminga, A., Lai, J.-S., Li, X., MacFarlane, A. J., Martinez, H., McNulty, H., Momoli, F., Mossey, P., Mullie, P., Munger, R., Parajuli, R. P., Kent, M. P., ... Little, J. (2026). Folate and global health umbrella review series, part 2: syntheses on cancers. Journal of Global Health, 16, 1-19. Article 4102. Advance online publication. https://doi.org/10.7189/jogh.16.04102

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title = "Folate and global health umbrella review series, part 2: syntheses on cancers",

abstract = "Background Folate has been examined extensively in relation to carcinogenesis due to its role in one-carbon metabolism impacting the synthesis of DNA and RNA, methylation processes, and genomic integrity. Current evidence on the relationship between folate status and the risk of cancer is equivocal: low or deficient folate status may contribute to an increased risk of cancers, while high-dose folic acid supplementation may have adverse effects on carcinogenesis. Methods We searched MEDLINE, Embase, CINAHL, the Cochrane Library, and the Database of Abstracts of Reviews of Effects up to February 2024 for systematic reviews and meta-analyses investigating the associations of folate (measured as dietary intake, supplementation, or blood concentrations) with any specific cancer outcome. Screening, data extraction, and risk of bias assessment were performed in duplicate. We assessed the credibility of the evidence using predefined criteria. Results We found 67 syntheses, of which 57 provided meta-analyses. Over half of the syntheses had a high risk of bias. We identified 168 unique associations (unique exposure - unique outcome - unique setting) across 10 cancer types, 3 system cancers, and total cancer. Of these, we assessed 15 directional associations (colorectal, oesophageal, and total cancers) to be at a highly suggestive level of credibility, and 17 directional and 10 null associations to be at a suggestive level of credibility. Conclusions The available evidence for each category of unique association was generally limited. Highly suggestive associations were found for oesophageal, colorectal, childhood brain and spinal tumours and total cancers. More robust primary studies are warranted to follow-up the signal of a positive relationship reported for prostate cancer warranting further research. Evidence was weak for all but colorectal and oesophageal cancers, or the central nervous system cancers in children. Registration PROSPERO: CRD42021265041.",

keywords = "Humans, Neoplasms, Folic Acid, Dietary Supplements, Global Health, Systematic Reviews as Topic, Folic Acid/administration \& dosage, Neoplasms/epidemiology",

author = "Samantha Yoo and Azita Montazeri and Derrick Bennett and Yacong Bo and Peizhan Chen and Susan Duthie and Natalie Jensen and Atipatsa Kaminga and Jun-Shi Lai and Xue Li and MacFarlane, \{Amanda J\} and Homero Martinez and Helene McNulty and Franco Momoli and Peter Mossey and Patrick Mullie and Ron Munger and Parajuli, \{Rajendra Prasad\} and Kent, \{Monique Potvin\} and Michele Rubini and Marjanne Senekal and Lindsey Sikora and Alain Stintzi and Evropi Theodoratou and Hui Wang and Chittaranjan Yajnik and Ann Yaktine and Julian Little",

note = "{\textcopyright} 2026 The Author(s)",

year = "2026",

month = feb,

day = "20",

doi = "10.7189/jogh.16.04102",

language = "English",

volume = "16",

pages = "1--19",

journal = "Journal of Global Health",

issn = "2047-2978",

publisher = "University of Edinburgh",

}

Yoo, S, Montazeri, A, Bennett, D, Bo, Y, Chen, P, Duthie, S, Jensen, N, Kaminga, A, Lai, J-S, Li, X, MacFarlane, AJ, Martinez, H, McNulty, H, Momoli, F, Mossey, P, Mullie, P, Munger, R, Parajuli, RP, Kent, MP, Rubini, M, Senekal, M, Sikora, L, Stintzi, A, Theodoratou, E, Wang, H, Yajnik, C, Yaktine, A & Little, J 2026, 'Folate and global health umbrella review series, part 2: syntheses on cancers', Journal of Global Health, vol. 16, 4102, pp. 1-19. https://doi.org/10.7189/jogh.16.04102

TY - JOUR

T1 - Folate and global health umbrella review series, part 2: syntheses on cancers

AU - Yoo, Samantha

AU - Montazeri, Azita

AU - Bennett, Derrick

AU - Bo, Yacong

AU - Chen, Peizhan

AU - Duthie, Susan

AU - Jensen, Natalie

AU - Kaminga, Atipatsa

AU - Lai, Jun-Shi

AU - Li, Xue

AU - MacFarlane, Amanda J

AU - Martinez, Homero

AU - McNulty, Helene

AU - Momoli, Franco

AU - Mossey, Peter

AU - Mullie, Patrick

AU - Munger, Ron

AU - Parajuli, Rajendra Prasad

AU - Kent, Monique Potvin

AU - Rubini, Michele

AU - Senekal, Marjanne

AU - Sikora, Lindsey

AU - Stintzi, Alain

AU - Theodoratou, Evropi

AU - Wang, Hui

AU - Yajnik, Chittaranjan

AU - Yaktine, Ann

AU - Little, Julian

PY - 2026/2/20

Y1 - 2026/2/20

N2 - Background Folate has been examined extensively in relation to carcinogenesis due to its role in one-carbon metabolism impacting the synthesis of DNA and RNA, methylation processes, and genomic integrity. Current evidence on the relationship between folate status and the risk of cancer is equivocal: low or deficient folate status may contribute to an increased risk of cancers, while high-dose folic acid supplementation may have adverse effects on carcinogenesis. Methods We searched MEDLINE, Embase, CINAHL, the Cochrane Library, and the Database of Abstracts of Reviews of Effects up to February 2024 for systematic reviews and meta-analyses investigating the associations of folate (measured as dietary intake, supplementation, or blood concentrations) with any specific cancer outcome. Screening, data extraction, and risk of bias assessment were performed in duplicate. We assessed the credibility of the evidence using predefined criteria. Results We found 67 syntheses, of which 57 provided meta-analyses. Over half of the syntheses had a high risk of bias. We identified 168 unique associations (unique exposure - unique outcome - unique setting) across 10 cancer types, 3 system cancers, and total cancer. Of these, we assessed 15 directional associations (colorectal, oesophageal, and total cancers) to be at a highly suggestive level of credibility, and 17 directional and 10 null associations to be at a suggestive level of credibility. Conclusions The available evidence for each category of unique association was generally limited. Highly suggestive associations were found for oesophageal, colorectal, childhood brain and spinal tumours and total cancers. More robust primary studies are warranted to follow-up the signal of a positive relationship reported for prostate cancer warranting further research. Evidence was weak for all but colorectal and oesophageal cancers, or the central nervous system cancers in children. Registration PROSPERO: CRD42021265041.

AB - Background Folate has been examined extensively in relation to carcinogenesis due to its role in one-carbon metabolism impacting the synthesis of DNA and RNA, methylation processes, and genomic integrity. Current evidence on the relationship between folate status and the risk of cancer is equivocal: low or deficient folate status may contribute to an increased risk of cancers, while high-dose folic acid supplementation may have adverse effects on carcinogenesis. Methods We searched MEDLINE, Embase, CINAHL, the Cochrane Library, and the Database of Abstracts of Reviews of Effects up to February 2024 for systematic reviews and meta-analyses investigating the associations of folate (measured as dietary intake, supplementation, or blood concentrations) with any specific cancer outcome. Screening, data extraction, and risk of bias assessment were performed in duplicate. We assessed the credibility of the evidence using predefined criteria. Results We found 67 syntheses, of which 57 provided meta-analyses. Over half of the syntheses had a high risk of bias. We identified 168 unique associations (unique exposure - unique outcome - unique setting) across 10 cancer types, 3 system cancers, and total cancer. Of these, we assessed 15 directional associations (colorectal, oesophageal, and total cancers) to be at a highly suggestive level of credibility, and 17 directional and 10 null associations to be at a suggestive level of credibility. Conclusions The available evidence for each category of unique association was generally limited. Highly suggestive associations were found for oesophageal, colorectal, childhood brain and spinal tumours and total cancers. More robust primary studies are warranted to follow-up the signal of a positive relationship reported for prostate cancer warranting further research. Evidence was weak for all but colorectal and oesophageal cancers, or the central nervous system cancers in children. Registration PROSPERO: CRD42021265041.

KW - Humans

KW - Neoplasms

KW - Folic Acid

KW - Dietary Supplements

KW - Global Health

KW - Systematic Reviews as Topic

KW - Folic Acid/administration & dosage

KW - Neoplasms/epidemiology

UR - https://www.scopus.com/pages/publications/105030785804

U2 - 10.7189/jogh.16.04102

DO - 10.7189/jogh.16.04102

M3 - Article

C2 - 41718012

SN - 2047-2978

VL - 16

SP - 1

EP - 19

JO - Journal of Global Health

JF - Journal of Global Health

M1 - 4102

ER -

Folate and global health umbrella review series, part 2: syntheses on cancers

Abstract

Bibliographical note

Data Availability Statement

Funding

UN SDGs

Keywords

Access to Document

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Cite this