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Characterization of Additive Gene-environment Interactions For Colorectal Cancer Risk.

About this Publication
Title
Characterization of Additive Gene-environment Interactions For Colorectal Cancer Risk.
Pubmed ID
39316822 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Epidemiology. 2025 Jan 1; Volume 36 (Issue 1): Pages 126-138
Authors
Thomas CE, Lin Y, Kim M, Kawaguchi ES, Qu C, Um CY, Lynch BM, Van Guelpen B, Tsilidis K, Carreras-Torres R, van Duijnhoven FJB, Sakoda LC, Campbell PT, Tian Y, Chang-Claude J, Bézieau S, Budiarto A, Palmer JR, Newcomb PA, Casey G, ...show more Le Marchandz L, Giannakis M, Li CI, Gsur A, Newton C, Obón-Santacana M, Moreno V, Vodicka P, Brenner H, Hoffmeister M, Pellatt AJ, Schoen RE, Dimou N, Murphy N, Gunter MJ, Castellví-Bel S, Figueiredo JC, Chan AT, Song M, Li L, Bishop DT, Gruber SB, Baurley JW, Bien SA, Conti DV, Huyghe JR, Kundaje A, Su YR, Wang J, Keku TO, Woods MO, Berndt SI, Chanock SJ, Tangen CM, Wolk A, Burnett-Hartman A, Wu AH, White E, Devall MA, Díez-Obrero V, Drew DA, Giovannucci E, Hidaka A, Kim AE, Lewinger JP, Morrison J, Ose J, Papadimitriou N, Pardamean B, Peoples AR, Ruiz-Narvaez EA, Shcherbina A, Stern MC, Chen X, Thomas DC, Platz EA, Gauderman WJ, Peters U, Hsu L
Affiliations
  • From the Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA.
  • Division of Biostatistics, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Department of Population Science, American Cancer Society, Atlanta, GA.
  • Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.
  • Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, UK.
  • Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.
  • Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
...show more
  • Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU) Nantes, Nantes, France.
  • Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
  • Slone Epidemiology Center at Boston University, Boston, MA.
  • Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
  • University of Hawaii Cancer Center, Honolulu, HI.
  • Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
  • Center for Cancer Research, Medical University of Vienna, Vienna, Austria.
  • Unit of Biomarkers and Suceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain.
  • Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Departments of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA.
  • Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
  • Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.
  • Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
  • Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
  • Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
  • Department of Family Medicine, University of Virginia, Charlottesville, VA.
  • Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
  • Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte CA.
  • Department of Genetics, Stanford University, Stanford, CA.
  • Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC.
  • Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • SWOG Statistical Center, Fred Hutchinson Cancer Center, Seattle, WA.
  • Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Institute for Health Research, Kaiser Permanente Colorado, Aurora, CO.
  • University of Southern California, Department of Population and Public Health Sciences, Los Angeles, CA.
  • Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
  • Clinical & Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
  • Harvard TH Chan School of Public Health.
  • Huntsman Cancer Institute, Salt Lake City, UT.
  • Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI.
  • Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA.
  • Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Abstract

BACKGROUND: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure.

METHODS: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk.

RESULTS: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking (RERI = 0.24, 95% confidence interval [CI] = 0.13, 0.36), ever smoking (0.11 [0.05, 0.16]), high body mass index (female 0.09 [0.05, 0.13], male 0.10 [0.05, 0.14]), or high red meat intake (highest versus lowest quartile 0.18 [0.09, 0.27]) was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/nonsteroidal anti-inflammatory drugs use (-0.16 [-0.20, -0.11]) or higher intake of fruit, fiber, or calcium (highest quartile versus lowest quartile -0.12 [-0.18, -0.050]; -0.16 [-0.23, -0.09]; -0.11 [-0.18, -0.05], respectively) than those with average genetic susceptibility.

CONCLUSIONS: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.

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