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Mendelian Randomization of Circulating Polyunsaturated Fatty Acids and Colorectal Cancer Risk.
Khankari, Nikhil K; Banbury, Barbara L; Borges, Maria C; Haycock, Philip; Albanes, Demetrius; Arndt, Volker; Berndt, Sonja I; Bézieau, Stéphane; Brenner, Hermann; Campbell, Peter T; Casey, Graham; Chan, Andrew T; Chang-Claude, Jenny; Conti, David V; Cotterchio, Michelle; English, Dallas R; Figueiredo, Jane C; Giles, Graham G; Giovannucci, Edward L; Gunter, Marc J; Hampe, Jochen; Hoffmeister, Michael; Hopper, John L; Jenkins, Mark A; Joshi, Amit D; Marchand, Loic Le; Lemire, Mathieu; Li, Christopher I; Li, Li; Lindblom, Annika; Martín, Vicente; Moreno, Victor; Newcomb, Polly A; Offit, Kenneth; Pharoah, Paul D P; Rennert, Gad; Sakoda, Lori C; Schafmayer, Clemens; Schmit, Stephanie L; Slattery, Martha L; Song, Mingyang; Thibodeau, Stephen N; Ulrich, Cornelia M; Weinstein, Stephanie J; White, Emily; Win, Aung Ko; Wolk, Alicja; Woods, Michael O; Wu, Anna H; Cai, Qiuyin.
Afiliação
  • Khankari NK; Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee. nikhil.khankari@vumc.org.
  • Banbury BL; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • Borges MC; Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
  • Haycock P; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
  • Albanes D; Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
  • Arndt V; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
  • Berndt SI; Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
  • Bézieau S; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Brenner H; Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
  • Campbell PT; Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU) Nantes, Nantes, France.
  • Casey G; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Chan AT; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
  • Chang-Claude J; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Conti DV; Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.
  • Cotterchio M; Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.
  • English DR; 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.
  • Giles GG; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Giovannucci EL; 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.
  • Hampe J; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Hoffmeister M; University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
  • Hopper JL; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Jenkins MA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Joshi AD; Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada.
  • Marchand LL; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Lemire M; Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Li CI; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
  • Li L; Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
  • Lindblom A; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Martín V; Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Moreno V; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
  • Newcomb PA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Offit K; Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Pharoah PDP; Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.
  • Rennert G; Department of Medicine, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.
  • Sakoda LC; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Schafmayer C; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Schmit SL; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Slattery ML; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
  • Song M; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
  • Thibodeau SN; University of Hawaii Cancer Center, Honolulu, Hawaii.
  • Ulrich CM; PanCuRx Translational Research Initiative, Ontario, Institute for Cancer Research, Toronto, Ontario, Canada.
  • Weinstein SJ; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
  • White E; Department of Family Medicine, University of Virginia, Charlottesville, Virginia.
  • Win AK; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
  • Wolk A; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Woods MO; Área de Medicina Preventiva y Salud Publica, Universidad de León, León, Spain.
  • Wu AH; Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
  • Cai Q; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
Cancer Epidemiol Biomarkers Prev ; 29(4): 860-870, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32051193
ABSTRACT

BACKGROUND:

Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk.

METHODS:

Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined.

RESULTS:

Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93-0.98; P = 5.2 × 10-4] and α-linolenic acid (ORALA = 0.95; 95% CI = 0.92-0.97; P = 5.4 × 10-5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03-1.08; P = 3.3 × 10-5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01-1.07; P = 2.5 × 10-3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01-1.06; P = 1.2 × 10-2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses.

CONCLUSIONS:

Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk. IMPACT The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs 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