Mendelian Randomization of Circulating Polyunsaturated Fatty Acids and Colorectal Cancer Risk.

Aged Anti-Inflammatory Agents, Non-Steroidal / therapeutic use Arachidonic Acid / blood Case-Control Studies Colorectal Neoplasms / blood Cyclooxygenase 2 / genetics Datasets as Topic Eicosapentaenoic Acid / blood Fatty Acids, Unsaturated / blood Female Genome-Wide Association Study Humans Male Mendelian Randomization Analysis Middle Aged Polymorphism, Single Nucleotide Protective Factors Risk Assessment / statistics & numerical data Risk Factors White People / genetics

Journal

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608

Informations de publication

Date de publication:
04 2020
Historique:
received: 26 07 2019
revised: 03 10 2019
accepted: 23 01 2020
pubmed: 14 2 2020
medline: 7 7 2021
entrez: 14 2 2020
Statut: ppublish

Résumé

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. 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. Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [OR 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. 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.

Sections du résumé

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 [OR
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.

Identifiants

DOI: 10.1158/1055-9965.EPI-19-0891 PMID: 32051193 PMC: PMC7125012
pubmed: 32051193
pii: 1055-9965.EPI-19-0891
doi: 10.1158/1055-9965.EPI-19-0891
pmc: PMC7125012
mid: NIHMS1554651
doi:

Substances chimiques

Anti-Inflammatory Agents, Non-Steroidal 0
Fatty Acids, Unsaturated 0
Arachidonic Acid 27YG812J1I
Eicosapentaenoic Acid AAN7QOV9EA
Cyclooxygenase 2 EC 1.14.99.1
PTGS2 protein, human EC 1.14.99.1
docosapentaenoic acid NS3OZT14QT

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

860-870

Subventions

Organisme : NHGRI NIH HHS
ID : U01 HG004446
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA074799
Pays : United States
Organisme : NCI NIH HHS
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Organisme : NCI NIH HHS
ID : R01 CA042182
Pays : United States
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ID : UM1 CA167552
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ID : HHSN268201100004C
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Organisme : Cancer Research UK
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Organisme : NCI NIH HHS
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Informations de copyright

©2020 American Association for Cancer Research.

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Auteurs

Nikhil K Khankari (NK)

Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee. nikhil.khankari@vumc.org.

Barbara L Banbury (BL)

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
ORCID: 0000-0001-7332-7117

Maria C Borges (MC)

Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
ORCID: 0000-0001-7785-4547

Philip Haycock (P)

Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
ORCID: 0000-0001-5001-3350

Demetrius Albanes (D)

Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.

Volker Arndt (V)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
ORCID: 0000-0001-9320-8684

Sonja I Berndt (SI)

Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.

Stéphane Bézieau (S)

Service de Génétique Médicale, Centre Hospitalier Universitaire (CHU) Nantes, Nantes, France.

Hermann Brenner (H)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
ORCID: 0000-0001-7494-9655

Peter T Campbell (PT)

Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia.

Graham Casey (G)

Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.

Andrew T Chan (AT)

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

Jenny Chang-Claude (J)

University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
ORCID: 0000-0001-8919-1971

David V Conti (DV)

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.

Michelle Cotterchio (M)

Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada.

Dallas R English (DR)

Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
ORCID: 0000-0001-7828-8188

Jane C Figueiredo (JC)

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Graham G Giles (GG)

Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
ORCID: 0000-0003-4946-9099

Edward L Giovannucci (EL)

Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

Marc J Gunter (MJ)

Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.

Jochen Hampe (J)

Department of Medicine, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.

Michael Hoffmeister (M)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
ORCID: 0000-0002-8307-3197

John L Hopper (JL)

Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.

Mark A Jenkins (MA)

Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.

Amit D Joshi (AD)

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

Loic Le Marchand (LL)

University of Hawaii Cancer Center, Honolulu, Hawaii.

Mathieu Lemire (M)

PanCuRx Translational Research Initiative, Ontario, Institute for Cancer Research, Toronto, Ontario, Canada.

Christopher I Li (CI)

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Li Li (L)

Department of Family Medicine, University of Virginia, Charlottesville, Virginia.

Annika Lindblom (A)

Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Vicente Martín (V)

Área de Medicina Preventiva y Salud Publica, Universidad de León, León, Spain.
ORCID: 0000-0003-0552-2804

Victor Moreno (V)

Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
ORCID: 0000-0002-2818-5487

Polly A Newcomb (PA)

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington.

Kenneth Offit (K)

Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
Department of Medicine, Weill Cornell Medical College, New York, New York.

Paul D P Pharoah (PDP)

Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
ORCID: 0000-0001-8494-732X

Gad Rennert (G)

Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.
Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Clalit National Cancer Control Center, Haifa, Israel.
ORCID: 0000-0002-8512-068X

Lori C Sakoda (LC)

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Division of Research, Kaiser Permanente Northern California, Oakland, California.
ORCID: 0000-0002-0900-5735

Clemens Schafmayer (C)

Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Stephanie L Schmit (SL)

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Martha L Slattery (ML)

Division of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, Utah.
ORCID: 0000-0002-1655-6543

Mingyang Song (M)

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.

Stephen N Thibodeau (SN)

Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Cornelia M Ulrich (CM)

Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.

Stephanie J Weinstein (SJ)

Division of Cancer Epidemiology and Genetics, NCI, NIH, Bethesda, Maryland.
ORCID: 0000-0002-3834-1535

Emily White (E)

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington.

Aung Ko Win (AK)

Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
ORCID: 0000-0002-2794-5261

Alicja Wolk (A)

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
ORCID: 0000-0001-7387-6845

Michael O Woods (MO)

Discipline of Genetics, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.

Anna H Wu (AH)

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.

Qiuyin Cai (Q)

Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.

Joshua C Denny (JC)

Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee.
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee.
ORCID: 0000-0002-3049-7332

Todd L Edwards (TL)

Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee.

Harvey J Murff (HJ)

Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.

Stephen B Gruber (SB)

Department of Medical Oncology, City of Hope National Medical Center, Duarte, California.

Ulrike Peters (U)

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington.

Wei Zheng (W)

Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Mendelian Randomization of Circulating...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antirhumatismaux › Anti-inflammatoires non stéroïdiens › Mendelian Randomization of Circulating...
questionsmedicales.fr › Lipides › Acides gras › Acides gras insaturés › Acides gras indispensables › Acides arachidoniques › Acide arachidonique › Mendelian Randomization of Circulating...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Mendelian Randomization of Circulating...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies du rectum › Tumeurs colorectales › Mendelian Randomization of Circulating...
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