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A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk.
Aglago, Elom K; Kim, Andre; Lin, Yi; Qu, Conghui; Evangelou, Marina; Ren, Yu; Morrison, John; Albanes, Demetrius; Arndt, Volker; Barry, Elizabeth L; Baurley, James W; Berndt, Sonja I; Bien, Stephanie A; Bishop, D Timothy; Bouras, Emmanouil; Brenner, Hermann; Buchanan, Daniel D; Budiarto, Arif; Carreras-Torres, Robert; Casey, Graham; Cenggoro, Tjeng Wawan; Chan, Andrew T; Chang-Claude, Jenny; Chen, Xuechen; Conti, David V; Devall, Matthew; Diez-Obrero, Virginia; Dimou, Niki; Drew, David; Figueiredo, Jane C; Gallinger, Steven; Giles, Graham G; Gruber, Stephen B; Gsur, Andrea; Gunter, Marc J; Hampel, Heather; Harlid, Sophia; Hidaka, Akihisa; Harrison, Tabitha A; Hoffmeister, Michael; Huyghe, Jeroen R; Jenkins, Mark A; Jordahl, Kristina; Joshi, Amit D; Kawaguchi, Eric S; Keku, Temitope O; Kundaje, Anshul; Larsson, Susanna C; Marchand, Loic Le; Lewinger, Juan Pablo.
Afiliação
  • Aglago EK; Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
  • Kim A; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Lin Y; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Qu C; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Evangelou M; Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
  • Ren Y; Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom.
  • Morrison J; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Albanes D; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Arndt V; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Barry EL; Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
  • Baurley JW; Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
  • Berndt SI; BioRealm LLC, Walnut, California.
  • Bien SA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Bishop DT; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Bouras E; Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
  • Brenner H; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
  • Buchanan DD; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Budiarto A; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
  • Carreras-Torres R; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Casey G; Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.
  • Cenggoro TW; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia.
  • Chan AT; Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
  • Chang-Claude J; Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
  • Chen X; Computer Science Department, School of Computer Science, Bina Nusantara University, Jakarta, Indonesia.
  • Conti DV; ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Devall M; Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, Girona, Spain.
  • Diez-Obrero V; Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia.
  • Dimou N; Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
  • Drew D; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Figueiredo JC; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
  • Gallinger S; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Giles GG; Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
  • Gruber SB; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Gsur A; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Gunter MJ; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Hampel H; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
  • Harlid S; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Hidaka A; Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.
  • Harrison TA; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Hoffmeister M; Department of Family Medicine, University of Virginia, Charlottesville, Virginia.
  • Huyghe JR; ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Jenkins MA; Unit of Biomarkers and Susceptibility (UBS), Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), L'Hospitalet del Llobregat, Barcelona, Spain.
  • Jordahl K; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.
  • Joshi AD; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
  • Kawaguchi ES; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
  • Keku TO; Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
  • Kundaje A; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Larsson SC; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Marchand LL; Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
  • Lewinger JP; Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Cancer Res ; 83(15): 2572-2583, 2023 08 01.
Article em En | MEDLINE | ID: mdl-37249599
ABSTRACT
Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer.

SIGNIFICANCE:

This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Obesidade Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Obesidade Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article