The association between genetically elevated polyunsaturated fatty acids and risk of cancer.
| Autor: | Haycock PC; MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol, United Kingdom. Electronic address: philip.haycock@bristol.ac.uk., Borges MC; MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol, United Kingdom., Burrows K; MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol, United Kingdom., Lemaitre RN; Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA., Burgess S; MRC Biostatistics Unit, University of Cambridge, USA., Khankari NK; Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Tsilidis KK; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., Gaunt TR; MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol, United Kingdom., Hemani G; MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol, United Kingdom., Zheng J; Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Truong T; Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, Team 'Exposome, Heredity, Cancer and Health', CESP, Villejuif, France., Birmann BM; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., OMara T; Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Medicine, Faculty of Health Sciences, University of Queensland, Australia., Spurdle AB; Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Medicine, Faculty of Health Sciences, University of Queensland, Australia., Iles MM; Leeds Institute for Data Analytics, University of Leeds, Leeds, UK; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK., Law MH; Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Biomedical Sciences, Faculty of Health, and Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia., Slager SL; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA., Saberi Hosnijeh F; Institute for Risk Assessment Sciences, Utrecht University, Netherlands., Mariosa D; Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France., Cotterchio M; Dalla Lana School of Public Health, University of Toronto, Canada; Prevention and Cancer Control, Cancer Care Ontario, Ontario Health, Toronto, ON, Canada., Cerhan JR; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA., Peters U; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, USA; Department of Epidemiology, School of Public Health, University of Washington, Seattle, USA., Enroth S; Department of Immunology, Genetics, and Pathology, Biomedical Center, Science for Life Laboratory (SciLifeLab) Uppsala, Uppsala University, Uppsala, Sweden., Gharahkhani P; Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston QLD, 4006, Australia., Le Marchand L; University of Hawaii Cancer Center, Honolulu, HI, USA., Williams AC; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Block RC; Department of Public Health Sciences, University of Rochester, NY, USA., Amos CI; Dan L Duncan Comprehensive Cancer Center Baylor College of Medicine, USA., Hung RJ; Lunenfeld-Tanenbaum Research Institute Mount Sinai Hospital and University of Toronto, Canada., Zheng W; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Gunter MJ; Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, Lyon, France., Smith GD; MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol, United Kingdom., Relton C; MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol, United Kingdom., Martin RM; MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, University of Bristol, Bristol, United Kingdom; The National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. |
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| Jazyk: | angličtina |
| Zdroj: | EBioMedicine [EBioMedicine] 2023 May; Vol. 91, pp. 104510. Date of Electronic Publication: 2023 Apr 20. |
| DOI: | 10.1016/j.ebiom.2023.104510 |
| Abstrakt: | Background: The causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain. Methods: Using a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures. Findings: Genetically elevated PUFA desaturase activity was associated (P < 0.0007) with higher risk (OR [95% confidence interval]) of colorectal cancer (1.09 [1.07-1.11]), esophageal squamous cell carcinoma (1.16 [1.06-1.26]), lung cancer (1.06 [1.03-1.08]) and basal cell carcinoma (1.05 [1.02-1.07]). There was little evidence for associations with reproductive cancers (OR = 1.00 [95% CI: 0.99-1.01]; P Interpretation: The PUFA biosynthesis pathway may be an intervention target for prevention of colorectal cancer and esophageal squamous cell carcinoma but with potential for increased risk of inflammatory bowel disease. Funding: Cancer Resesrch UK (C52724/A20138, C18281/A19169). UK Medical Research Council (MR/P014054/1). National Institute for Health Research (NIHR202411). UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4). National Cancer Institute (R00 CA215360). National Institutes of Health (U01 CA164973, R01 CA60987, R01 CA72520, U01 CA74806, R01 CA55874, U01 CA164973 and U01 CA164973). Competing Interests: Declaration of interests TRG has received funding from the Medical Research Council, Cancer Research UK and Biogen. BMB has received funding from the US National Institutes of Health/National Cancer Institute, American Institute of Cancer Research and Harvard Chan-NIEHS Center. JRC has received funding from the National Cancer Institute. GDS has received funding from the Medical Research Council. PG has received funding from the National Health and Medical Research Council. RM and PCH have received funding from Cancer Research UK. SB has received funding from the Wellcome Trust and the Medical Research Council. GDS reports Scientific Advisory Board Membership for Relation Therapeutics and Insitro. (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Databáze: | MEDLINE |
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