Evidence map›Paper›PMID 39025327›Full record

ArticleThe American journal of clinical nutrition2024

Folate intake and colorectal cancer risk according to genetic subtypes defined by targeted tumor sequencing.

Elom K Aglago, Conghui Qu, Sophia Harlid, Amanda I Phipps, Robert S Steinfelder, Shuji Ogino, Claire E Thomas, Li Hsu, Amanda E Toland, Hermann Brenner and 33 more

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Article in The American journal of clinical nutrition, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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2 citing papers in PubMed.

  1. Article
  2. Metabolites · 2025
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4 · The record

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5 · Who and what money

Authors and funding

43 authors.

Elom K AglagoDepartment of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom. Electronic address: k.aglago@imperial.ac.uk.
Conghui QuPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.
Sophia HarlidDepartment of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.
Amanda I PhippsPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States; Department of Epidemiology, University of Washington, Seattle, WA, United States.
Robert S SteinfelderPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.
Shuji OginoProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Broad Institute of MIT and Harvard, Cambridge, MA, United States.
Claire E ThomasPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.
Li HsuPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States; Department of Biostatistics, University of Washington, Seattle, WA, United States.
Amanda E TolandDepartment of Cancer Biology and Genetics and Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Sonja I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
Daniel D BuchananColorectal Oncogenomics Group, Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia; University of Melbourne Centre for Cancer Research, The University of Melbourne, Parkville, VIC, Australia; Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, Australia.
Peter T CampbellDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States.
Yin CaoDivision of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, United States; Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO, United States; Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States.
Andrew T ChanDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Broad Institute of MIT and Harvard, Cambridge, MA, United States; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, United States.
David A DrewClinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Jane C FigueiredoDepartment of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Amy J FrenchDivision of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.
Steven GallingerLunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
Peter GeorgesonColorectal Oncogenomics Group, Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia; University of Melbourne Centre for Cancer Research, The University of Melbourne, Parkville, VIC, Australia.
Marios GiannakisBroad Institute of MIT and Harvard, Cambridge, MA, United States; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Ellen L GoodeDepartment of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN, United States.
Stephen B GruberDepartment of Medical Oncology & Therapeutics Research and Center for Precision Medicine, City of Hope National Medical Center, Duarte, CA, United States.
Marc J GunterDepartment of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
Tabitha A HarrisonPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.
Michael HoffmeisterDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Wen-Yi HuangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
Meredith Aj HullarPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.
Jeroen R HuyghePublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.
Mark A JenkinsCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
Brigid M LynchCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
Victor MorenoUnit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine and health Sciences and Universitat de Barcelona Institute of Complex Systems (UBICS), University of Barcelona (UB), L'Hospitalet de Llobregat, Barcelona, Spain.
Neil MurphyNutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
Christina C NewtonOntario Institute for Cancer Research, Toronto, ON, Canada.
Jonathan A NowakProgram in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Mireia Obón-SantacanaUnit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain; ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Wei SunPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.
Tomotaka UgaiDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
Caroline Y UmDepartment of Population Science, American Cancer Society, Atlanta, Georgia.
Syed H ZaidiOntario Institute for Cancer Research, Toronto, ON, Canada.
Konstantinos K TsilidisDepartment of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Greece.
Bethany van GuelpenDepartment of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden; Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
Ulrike PetersPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States; Department of Epidemiology, University of Washington, Seattle, WA, United States.

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3M
Data sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8M
Using Functional Genomics to Inform Gene Environment Interactions for Colorectal CancerR01CA201407 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI CASEY, GRAHAM, GAUDERMAN, WILLIAM JAMES · 2016 to 2020
$9.6M
An integrative omics approach to investigate gene-environment interaction in colorectal cancer riskR01CA273198 · NCI · FRED HUTCHINSON CANCER CENTER · PI William JAMES GAUDERMAN, ULRIKE PETERS · 2023 to 2026
$3.5M
NCI NIH HHS P30 CA015083NCI NIH HHS R01 CA201407NCI NIH HHS R01 CA273198NCI NIH HHS U01 CA167551World Health Organization 001
6 · The paper itself

Abstract

backgroundFolate is involved in multiple genetic, epigenetic, and metabolic processes, and inadequate folate intake has been associated with an increased risk of cancer.

objectiveWe examined whether folate intake is differentially associated with colorectal cancer (CRC) risk according to somatic mutations in genes linked to CRC using targeted sequencing.

designParticipants within 2 large CRC consortia with available information on dietary folate, supplemental folic acid, and total folate intake were included. Colorectal tumor samples from cases were sequenced for the presence of nonsilent mutations in 105 genes and 6 signaling pathways (IGF2/PI3K, MMR, RTK/RAS, TGF-β, WNT, and TP53/ATM). Multinomial logistic regression models were analyzed comparing mutated/nonmutated CRC cases to controls to compute multivariable-adjusted odds ratios (ORs) with 95% confidence interval (CI). Heterogeneity of associations of mutated compared with nonmutated CRC cases was tested in case-only analyses using logistic regression. Analyses were performed separately in hypermutated and nonhypermutated tumors, because they exhibit different clinical behaviors.

resultsWe included 4339 CRC cases (702 hypermutated tumors, 16.2%) and 11,767 controls. Total folate intake was inversely associated with CRC risk (OR = 0.93; 95% CI: 0.90, 0.96). Among hypermutated tumors, 12 genes (AXIN2, B2M, BCOR, CHD1, DOCK3, FBLN2, MAP3K21, POLD1, RYR1, TET2, UTP20, and ZNF521) showed nominal statistical significance (P < 0.05) for heterogeneity by mutation status, but none remained significant after multiple testing correction. Among these genetic subtypes, the associations between folate variables and CRC were mostly inverse or toward the null, except for tumors mutated for DOCK3 (supplemental folic acid), CHD1 (total folate), and ZNF521 (dietary folate) that showed positive associations. We did not observe differential associations in analyses among nonhypermutated tumors, or according to the signaling pathways.

conclusionsFolate intake was not differentially associated with CRC risk according to mutations in the genes explored. The nominally significant differential mutation effects observed in a few genes warrants further investigation.

Indexed as

Colorectal NeoplasmsFolic AcidMutationAdultAgedCase-Control StudiesDietDietary SupplementsFemaleHumansLogistic ModelsMaleMiddle AgedRisk FactorsSignal TransductionFolic Acidcolorectal cancerfolatefolic acidmolecular subtypessomatic mutationstumor

Identifiers

PMID39025327
PMCPMC11393398

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