Journal Article

DKFZ-2026-02813

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Folate and folic acid intake in relation to molecular subtypes of colorectal cancer: pooled analyses of up to 8970 cases and 8098 control participants.

Van Guelpen, B. ; Gylling, B. ; Harlid, S. ; Qu, C. ; Aglago, E. K. ; Winkvist, A. ; Tsilidis, K. K. ; Murphy, N. ; Berndt, S. I. ; Brenner, H.DKFZ* ; Buchanan, D. D. ; Campbell, P. T. ; Chan, A. T. ; Drew, D. A. ; French, A. J. ; Gallinger, S. ; Georgeson, P. ; Giannakis, M. ; Hoffmeister, M.DKFZ* ; Hsu, L. ; Huang, W.-Y. ; Hullar, M. ; Huyghe, J. R. ; Jayasekara, H. ; Jenkins, M. A. ; Lin, Y. ; Moreno, V. ; Newcomb, P. A. ; Newton, C. ; Nowak, J. A. ; Obón-Santacana, M. ; Ogino, S. ; Pellatt, A. ; Potter, J. D. ; Sakoda, L. C. ; Schoen, R. E. ; Song, M. ; Steinfelder, R. S. ; Thomas, C. E. ; Toland, A. E. ; Trinh, Q. M. ; Ugai, T. ; Um, C. Y. ; Woods, M. O. ; Zaidi, S. H. ; Harrison, T. A. ; Phipps, A. I. ; Peters, U.

2026
Elsevier Amsterdam

Abstract: Higher intakes of the B-vitamin folate are associated with modest reductions in colorectal cancer risk. Intertumoral heterogeneity has been suggested to affect the relationship, but studies to date have been limited in number and size.This study aimed to determine whether associations between intake of the B-vitamin folate (from diet and folic acid supplements) and the risk of colorectal cancer vary by tumor molecular marker status for BRAF and KRAS mutations, microsatellite instability (MSI), and/or the CpG island methylator phenotype (CIMP).The full study population included 8970 colorectal cancer cases and 8098 control participants from observational case-control and cohort studies within the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colon Cancer Family Registry (CCFR). Folate intake was assessed by food frequency questionnaire or diet history. Multivariable odds ratios (OR) and 95% confidence intervals (CIs) were estimated using multinomial logistic regression. Differences in associations between tumor subtypes were assessed using case-only logistic regression.Total folate intake and folate supplement use were inversely associated with the risk of colorectal cancer, whereas the relationship for dietary folate was weaker. These associations did not vary substantially among CRC subtypes defined by individual tumor markers. Possible heterogeneity was observed only for CIMP, with a stronger inverse association between total folate intake and CIMP-low/negative compared to CIMP-high colorectal cancer (pdifference=0.07). Associations were also inverse for total folate and subtypes defined by marker combinations, except for a null association for the less common Jass Type 2 subtype of MSS/MSI-low, CIMP-high, BRAF-mutated, KRAS-wildtype (pdifference=0.06 compared to the traditional adenoma-carcinoma pathway).Overall, the putative protective effect of folate intake in colorectal cancer development appears to be broad, not limited to specific subtypes defined by BRAF, KRAS, MSI, and CIMP status, or combinations of these markers, in the tumor.

Keyword(s): B-vitamins ; colorectal cancer ; diet ; etiology ; folate ; folic acid ; molecular subtypes ; one-carbon metabolism ; risk factors

Note: epub

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Contributing Institute(s):

1. Koordinierungsstelle der Cancer Prevention GS (M320)
2. Klinische Epidemiologie der Krebsfrüherkennung (C070)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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