Skip to Main Content

An official website of the United States government

Probing the diabetes and colorectal cancer relationship using gene - environment interaction analyses.

About this Publication
Title
Probing the diabetes and colorectal cancer relationship using gene - environment interaction analyses.
Pubmed ID
37365285 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Br J Cancer. 2023 Aug; Volume 129 (Issue 3): Pages 511-520
Authors
Dimou N, Kim AE, Flanagan O, Murphy N, Diez-Obrero V, Shcherbina A, Aglago EK, Bouras E, Campbell PT, Casey G, Gallinger S, Gruber SB, Jenkins MA, Lin Y, Moreno V, Ruiz-Narvaez E, Stern MC, Tian Y, Tsilidis KK, Arndt V, ...show more Barry EL, Baurley JW, Berndt SI, Bézieau S, Bien SA, Bishop DT, Brenner H, Budiarto A, Carreras-Torres R, Cenggoro TW, Chan AT, Chang-Claude J, Chanock SJ, Chen X, Conti DV, Dampier CH, Devall M, Drew DA, Figueiredo JC, Giles GG, Gsur A, Harrison TA, Hidaka A, Hoffmeister M, Huyghe JR, Jordahl K, Kawaguchi E, Keku TO, Larsson SC, Le Marchand L, Lewinger JP, Li L, Mahesworo B, Morrison J, Newcomb PA, Newton CC, Obon-Santacana M, Ose J, Pai RK, Palmer JR, Papadimitriou N, Pardamean B, Peoples AR, Pharoah PDP, Platz EA, Potter JD, Rennert G, Scacheri PC, Schoen RE, Su YR, Tangen CM, Thibodeau SN, Thomas DC, Ulrich CM, Um CY, van Duijnhoven FJB, Visvanathan K, Vodicka P, Vodickova L, White E, Wolk A, Woods MO, Qu C, Kundaje A, Hsu L, Gauderman WJ, Gunter MJ, Peters U
Affiliations
  • Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France. DimouN@iarc.who.int.
  • Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
  • Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology, Barcelona, 08908, Spain.
  • Department of Genetics, Stanford University, Stanford, CA, USA.
  • School of Public Health, Imperial College London, London, United Kingdom.
  • Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
  • Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Department of Public Health Sciences, Center for Public Health Genomics, Charlottesville, VA, USA.
  • Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
...show more
  • Center for Precision Medicine, Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
  • Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, 08908, Spain.
  • Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Department of Population and Public Health Sciences & USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
  • Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Nantes Université, CHU Nantes, Service de Génétique médicale, F-44000, Nantes, France.
  • Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, 8908, Barcelona, Spain.
  • Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Department of Family Medicine, University of Virginia, Charlottesville, VA, USA.
  • Clinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Center for Cancer Research, Medical University of Vienna, Vienna, Austria.
  • Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
  • Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Department of Population Science, American Cancer Society, Atlanta, GA, USA.
  • Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Avda Gran Via Barcelona 199-203, 08908L'Hospitalet de Llobregat, Barcelona, Spain.
  • Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
  • Slone Epidemiology Center at Boston University, Boston, MA, USA.
  • Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • 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.
  • Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
  • Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  • Biostatistics Division, Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
  • SWOG Statistical Center, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.
  • Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
  • Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
  • Memorial University of Newfoundland, Discipline of Genetics, St. John's, NL, Canada.
Abstract

BACKGROUND: Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis.

METHODS: We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test).

RESULTS: Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177, SLC30A8 - ORAA: 1.62, 95% CI: 1.34-1.96; ORAG: 1.41, 95% CI: 1.30-1.54; ORGG: 1.22, 95% CI: 1.13-1.31; p-value3-d.f.: 5.46 × 10-11) and 13q14.13 (rs9526201, LRCH1 - ORGG: 2.11, 95% CI: 1.56-2.83; ORGA: 1.52, 95% CI: 1.38-1.68; ORAA: 1.13, 95% CI: 1.06-1.21; p-value2-d.f.: 7.84 × 10-09).

DISCUSSION: These results suggest that variation in genes related to insulin signaling (SLC30A8) and immune function (LRCH1) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.

Related CDAS Studies
Related CDAS Projects