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Exploratory Genome-Wide Interaction Analysis of Nonsteroidal Anti-inflammatory Drugs and Predicted Gene Expression on Colorectal Cancer Risk.
Wang, Xiaoliang; Su, Yu-Ru; Petersen, Paneen S; Bien, Stephanie; Schmit, Stephanie L; Drew, David A; Albanes, Demetrius; Berndt, Sonja I; Brenner, Hermann; Campbell, Peter T; Casey, Graham; Chang-Claude, Jenny; Gallinger, Steven J; Gruber, Stephen B; Haile, Robert W; Harrison, Tabitha A; Hoffmeister, Michael; Jacobs, Eric J; Jenkins, Mark A; Joshi, Amit D; Li, Li; Lin, Yi; Lindor, Noralane M; Marchand, Loïc Le; Martin, Vicente; Milne, Roger; Maclnnis, Robert; Moreno, Victor; Nan, Hongmei; Newcomb, Polly A; Potter, John D; Rennert, Gad; Rennert, Hedy; Slattery, Martha L; Thibodeau, Steve N; Weinstein, Stephanie J; Woods, Michael O; Chan, Andrew T; White, Emily; Hsu, Li; Peters, Ulrike.
Afiliação
  • Wang X; Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. xwang23@fredhutch.org.
  • Su YR; Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.
  • Petersen PS; Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Bien S; Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Schmit SL; Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.
  • Drew DA; Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Albanes D; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
  • Berndt SI; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.
  • Brenner H; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
  • Campbell PT; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Casey G; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Chang-Claude J; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Gallinger SJ; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
  • Gruber SB; German Cancer Consortium (DKTK), Heidelberg, Germany.
  • Haile RW; Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
  • Harrison TA; Public Health Sciences, University of Virginia, Charlottesville, Virginia.
  • Hoffmeister M; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Jacobs EJ; University Cancer Center Hamburg, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
  • Jenkins MA; Department of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada.
  • Joshi AD; Division of General Surgery, Toronto General Hospital, Toronto, Ontario, Canada.
  • Li L; Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Lin Y; Department of Health Research and Policy (Epidemiology), Stanford University School of Medicine, Palo Alto, California.
  • Lindor NM; Department of Medicine (Oncology), Stanford Cancer Institute, Palo Alto, California.
  • Marchand LL; Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Martin V; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Milne R; Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
  • Maclnnis R; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia.
  • Moreno V; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
  • Nan H; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
  • Newcomb PA; Department of Family Medicine, University of Virginia, Charlottesville, Virginia.
  • Potter JD; Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Rennert G; Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona.
  • Rennert H; Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
  • Slattery ML; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
  • Thibodeau SN; Biomedicine Institute (IBIOMED), University of León, León, Spain.
  • Weinstein SJ; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Woods MO; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Chan AT; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
  • White E; Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
  • Hsu L; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
  • Peters U; Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana.
Cancer Epidemiol Biomarkers Prev ; 29(9): 1800-1808, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32651213
ABSTRACT

BACKGROUND:

Regular use of nonsteroidal anti-inflammatory drugs (NSAID) is associated with lower risk of colorectal cancer. Genome-wide interaction analysis on single variants (G × E) has identified several SNPs that may interact with NSAIDs to confer colorectal cancer risk, but variations in gene expression levels may also modify the effect of NSAID use. Therefore, we tested interactions between NSAID use and predicted gene expression levels in relation to colorectal cancer risk.

METHODS:

Genetically predicted gene expressions were tested for interaction with NSAID use on colorectal cancer risk among 19,258 colorectal cancer cases and 18,597 controls from 21 observational studies. A Mixed Score Test for Interactions (MiSTi) approach was used to jointly assess G × E effects which are modeled via fixed interaction effects of the weighted burden within each gene set (burden) and residual G × E effects (variance). A false discovery rate (FDR) at 0.2 was applied to correct for multiple testing.

RESULTS:

Among the 4,840 genes tested, genetically predicted expression levels of four genes modified the effect of any NSAID use on colorectal cancer risk, including DPP10 (PG×E = 1.96 × 10-4), KRT16 (PG×E = 2.3 × 10-4), CD14 (PG×E = 9.38 × 10-4), and CYP27A1 (PG×E = 1.44 × 10-3). There was a significant interaction between expression level of RP11-89N17 and regular use of aspirin only on colorectal cancer risk (PG×E = 3.23 × 10-5). No interactions were observed between predicted gene expression and nonaspirin NSAID use at FDR < 0.2.

CONCLUSIONS:

By incorporating functional information, we discovered several novel genes that interacted with NSAID use. IMPACT These findings provide preliminary support that could help understand the chemopreventive mechanisms of NSAIDs on colorectal cancer.
Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo de etiologia / Estudo observacional / Estudo prognóstico / Fatores de risco Idioma: Inglês Revista: Cancer Epidemiol Biomarkers Prev Assunto da revista: Bioquímica / Epidemiologia / Neoplasias Ano de publicação: 2020 Tipo de documento: Artigo

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Tipo de estudo: Estudo de etiologia / Estudo observacional / Estudo prognóstico / Fatores de risco Idioma: Inglês Revista: Cancer Epidemiol Biomarkers Prev Assunto da revista: Bioquímica / Epidemiologia / Neoplasias Ano de publicação: 2020 Tipo de documento: Artigo