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Genome-wide interaction study of dietary intake of fibre, fruits, and vegetables with risk of colorectal cancer.

About this Publication
Title
Genome-wide interaction study of dietary intake of fibre, fruits, and vegetables with risk of colorectal cancer.
Pubmed ID
38749303 (View this publication on the PubMed website)
Digital Object Identifier
Publication
EBioMedicine. 2024 Jun; Volume 104: Pages 105146
Authors
Papadimitriou N, Kim A, Kawaguchi ES, Morrison J, Diez-Obrero V, Albanes D, Berndt SI, Bézieau S, Bien SA, Bishop DT, Bouras E, Brenner H, Buchanan DD, Campbell PT, Carreras-Torres R, Chan AT, Chang-Claude J, Conti DV, Devall MA, Dimou N, ...show more Drew DA, Gruber SB, Harrison TA, Hoffmeister M, Huyghe JR, Joshi AD, Keku TO, Kundaje A, Küry S, Le Marchand L, Lewinger JP, Li L, Lynch BM, Moreno V, Newton CC, Obón-Santacana M, Ose J, Pellatt AJ, Peoples AR, Platz EA, Qu C, Rennert G, Ruiz-Narvaez E, Shcherbina A, Stern MC, Su YR, Thomas DC, Thomas CE, Tian Y, Tsilidis KK, Ulrich CM, Um CY, Visvanathan K, Wang J, White E, Woods MO, Schmit SL, Macrae F, Potter JD, Hopper JL, Peters U, Murphy N, Hsu L, Gunter MJ, Gauderman WJ
Affiliations
  • Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
  • Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology, Barcelona, 08908, Spain; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute, Barcelona, 08908, Spain; Consortium for Biomedical Research in Epidemiology and Public Health, Barcelona, 08908, 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, 08908, Barcelona, Spain.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU) Nantes, Nantes, France.
  • Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
  • Division 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 Tumour Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Colorectal Oncogenomics Group, Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Parkville, Australia; University of Melbourne Centre for Cancer Research, The University of Melbourne, Parkville, Australia; Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
...show more
  • Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute, Barcelona, 08908, Spain; Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), 17190 Salt, Girona, Spain.
  • Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
  • Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA; Department of Public Health Sciences, Center for Public Health Genomics, Charlottesville, VA, USA.
  • Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Department of Medical Oncology & Therapeutics Research and Center for Precision Medicine, City of Hope National Medical Center, Duarte, CA, USA.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
  • Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
  • Department of Genetics, Stanford University, Stanford, CA, USA; Department of Computer Science, Stanford University, Stanford, CA, USA.
  • University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Department of Family Medicine, University of Virginia, Charlottesville, VA, USA.
  • Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Department of Population Science, American Cancer Society, Atlanta, GA, USA.
  • Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology, Barcelona, 08908, Spain; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute, Barcelona, 08908, Spain; Consortium for Biomedical Research in Epidemiology and Public Health, Barcelona, 08908, Spain.
  • Huntsman Cancer Institute, Salt Lake City, UT, USA; Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
  • Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Clalit National Cancer Control Center, Haifa, Israel.
  • Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Department of Genetics, Stanford University, Stanford, CA, USA.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; School of Public Health, Capital Medical University, Beijing, China.
  • Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, UK.
  • Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
  • Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA.
  • Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada.
  • Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA; Population and Cancer Prevention Program, Case Comprehensive Cancer Center, Cleveland, OH, USA.
  • The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
  • Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia; Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea.
  • Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA. Electronic address: upeters@fredhutch.org.
  • Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Biostatistics, University of Washington, Seattle, WA, USA. Electronic address: lih@fredhutch.org.
  • Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France; Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, UK. Electronic address: m.gunter@imperial.ac.uk.
  • Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: jimg@usc.edu.
Abstract

BACKGROUND: Consumption of fibre, fruits and vegetables have been linked with lower colorectal cancer (CRC) risk. A genome-wide gene-environment (G × E) analysis was performed to test whether genetic variants modify these associations.

METHODS: A pooled sample of 45 studies including up to 69,734 participants (cases: 29,896; controls: 39,838) of European ancestry were included. To identify G × E interactions, we used the traditional 1--degree-of-freedom (DF) G × E test and to improve power a 2-step procedure and a 3DF joint test that investigates the association between a genetic variant and dietary exposure, CRC risk and G × E interaction simultaneously.

FINDINGS: The 3-DF joint test revealed two significant loci with p-value <5 × 10-8. Rs4730274 close to the SLC26A3 gene showed an association with fibre (p-value: 2.4 × 10-3) and G × fibre interaction with CRC (OR per quartile of fibre increase = 0.87, 0.80, and 0.75 for CC, TC, and TT genotype, respectively; G × E p-value: 1.8 × 10-7). Rs1620977 in the NEGR1 gene showed an association with fruit intake (p-value: 1.0 × 10-8) and G × fruit interaction with CRC (OR per quartile of fruit increase = 0.75, 0.65, and 0.56 for AA, AG, and GG genotype, respectively; G × E -p-value: 0.029).

INTERPRETATION: We identified 2 loci associated with fibre and fruit intake that also modify the association of these dietary factors with CRC risk. Potential mechanisms include chronic inflammatory intestinal disorders, and gut function. However, further studies are needed for mechanistic validation and replication of findings.

FUNDING: National Institutes of Health, National Cancer Institute. Full funding details for the individual consortia are provided in acknowledgments.

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