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Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region.
Jordahl, Kristina M; Shcherbina, Anna; Kim, Andre E; Su, Yu-Ru; Lin, Yi; Wang, Jun; Qu, Conghui; Albanes, Demetrius; Arndt, Volker; Baurley, James W; Berndt, Sonja I; Bien, Stephanie A; Bishop, D Timothy; Bouras, Emmanouil; Brenner, Hermann; Buchanan, Daniel D; Budiarto, Arif; Campbell, Peter T; Carreras-Torres, Robert; Casey, Graham; Cenggoro, Tjeng Wawan; Chan, Andrew T; Conti, David V; Dampier, Christopher H; Devall, Matthew A; Díez-Obrero, Virginia; Dimou, Niki; Drew, David A; Figueiredo, Jane C; Gallinger, Steven; Giles, Graham G; Gruber, Stephen B; Gsur, Andrea; Gunter, Marc J; Hampel, Heather; Harlid, Sophia; Harrison, Tabitha A; Hidaka, Akihisa; Hoffmeister, Michael; Huyghe, Jeroen R; Jenkins, Mark A; Joshi, Amit D; Keku, Temitope O; Larsson, Susanna C; Le Marchand, Loic; Lewinger, Juan Pablo; Li, Li; Mahesworo, Bharuno; Moreno, Victor; Morrison, John L.
Afiliação
  • Jordahl KM; Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.
  • Shcherbina A; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Kim AE; Department of Genetics, Stanford University, Stanford, California.
  • Su YR; Department of Computer Science, Stanford University, Stanford, California.
  • Lin Y; Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Wang J; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Qu C; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Albanes D; Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Arndt V; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Baurley JW; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Berndt SI; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Bien SA; Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
  • Bishop DT; BioRealm LLC, Walnut, California.
  • Bouras E; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Brenner H; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Buchanan DD; Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
  • Budiarto A; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
  • Campbell PT; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Carreras-Torres R; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
  • Casey G; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Cenggoro TW; Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.
  • Chan AT; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia.
  • Conti DV; Genetic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
  • Dampier CH; Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
  • Devall MA; Computer Science Department, School of Computer Science, Bina Nusantara University, Jakarta, Indonesia.
  • Díez-Obrero V; Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
  • Dimou N; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Drew DA; Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.
  • Figueiredo JC; Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
  • Gallinger S; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Giles GG; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
  • Gruber SB; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Gsur A; Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
  • Gunter MJ; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Hampel H; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Harlid S; Department of Preventive Medicine and USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Harrison TA; Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.
  • Hidaka A; Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.
  • Hoffmeister M; Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
  • Huyghe JR; Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
  • Jenkins MA; 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.
  • Keku TO; Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
  • Larsson SC; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Le Marchand L; Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
  • Lewinger JP; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Li L; Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
  • Mahesworo B; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Moreno V; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Morrison JL; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
Cancer Epidemiol Biomarkers Prev ; 31(5): 1077-1089, 2022 05 04.
Article em En | MEDLINE | ID: mdl-35438744
BACKGROUND: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. METHODS: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. RESULTS: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06-1.17; OR for AA genotype = 1.22; 95% CI, 1.14-1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. CONCLUSIONS: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. IMPACT: The study identifies multifaceted evidence of a possible functional effect for rs1318920.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Cancer Epidemiol Biomarkers Prev Assunto da revista: BIOQUIMICA / EPIDEMIOLOGIA / NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Cancer Epidemiol Biomarkers Prev Assunto da revista: BIOQUIMICA / EPIDEMIOLOGIA / NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article País de publicação: Estados Unidos