Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis

Sebastian May-Wilson; Amit Sud; Philip J Law; Kimmo Palin; Sari Tuupanen; Alexandra Gylfe; Ulrika A Hänninen; Tatiana Cajuso; Tomas Tanskanen; Johanna Kondelin; Eevi Kaasinen; Antti-Pekka Sarin; Johan G Eriksson; Harri Rissanen; Paul Knekt; Eero Pukkala; Pekka Jousilahti; Veikko Salomaa; Samuli Ripatti; Aarno Palotie; Laura Renkonen-Sinisalo; Anna Lepistö; Jan Böhm; Jukka-Pekka Mecklin; Nada A Al-Tassan; Claire Palles; Susan M Farrington; Maria N Timofeeva; Brian F Meyer; Salma M Wakil; Harry Campbell; Christopher G Smith; Shelley Idziaszczyk; Timothy S Maughan; David Fisher; Rachel Kerr; David Kerr; Michael N Passarelli; Jane C Figueiredo; Daniel D Buchanan; Aung K Win; John L Hopper; Mark A Jenkins; Noralane M Lindor; Polly A Newcomb; Steven Gallinger; David Conti; Fred Schumacher; Graham Casey; Lauri A Aaltonen; Jeremy P Cheadle; Ian P Tomlinson; Malcolm G Dunlop; Richard S Houlston

doi:10.1016/j.ejca.2017.07.034

Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis

Eur J Cancer. 2017 Oct:84:228-238. doi: 10.1016/j.ejca.2017.07.034. Epub 2017 Aug 19.

Authors

Sebastian May-Wilson¹, Amit Sud¹, Philip J Law¹, Kimmo Palin², Sari Tuupanen², Alexandra Gylfe², Ulrika A Hänninen², Tatiana Cajuso², Tomas Tanskanen², Johanna Kondelin², Eevi Kaasinen², Antti-Pekka Sarin³, Johan G Eriksson⁴, Harri Rissanen⁵, Paul Knekt⁵, Eero Pukkala⁶, Pekka Jousilahti⁵, Veikko Salomaa⁵, Samuli Ripatti⁷, Aarno Palotie⁸, Laura Renkonen-Sinisalo⁹, Anna Lepistö⁹, Jan Böhm¹⁰, Jukka-Pekka Mecklin¹¹, Nada A Al-Tassan¹², Claire Palles¹³, Susan M Farrington¹⁴, Maria N Timofeeva¹⁴, Brian F Meyer¹², Salma M Wakil¹², Harry Campbell¹⁵, Christopher G Smith¹⁶, Shelley Idziaszczyk¹⁶, Timothy S Maughan¹⁷, David Fisher¹⁸, Rachel Kerr¹⁹, David Kerr²⁰, Michael N Passarelli²¹, Jane C Figueiredo²², Daniel D Buchanan²³, Aung K Win²⁴, John L Hopper²⁴, Mark A Jenkins²⁴, Noralane M Lindor²⁵, Polly A Newcomb²⁶, Steven Gallinger²⁷, David Conti²⁸, Fred Schumacher²⁸, Graham Casey²⁹, Lauri A Aaltonen², Jeremy P Cheadle¹⁶, Ian P Tomlinson¹³, Malcolm G Dunlop¹⁴, Richard S Houlston³⁰

Affiliations

¹ Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK.
² Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, 00014, Finland; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, 00014, Finland.
³ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, 00014, Finland.
⁴ National Institute for Health and Welfare, Helsinki, 00271, Finland; Folkhälsan Research Centre, Helsinki, 00250, Finland; Unit of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, 00014, Finland.
⁵ National Institute for Health and Welfare, Helsinki, 00271, Finland.
⁶ Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, 00130, Finland; School of Health Sciences, University of Tampere, Tampere, 33014, Finland.
⁷ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, 00014, Finland; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK; Department of Public Health, University of Helsinki, Helsinki, 00014, Finland.
⁸ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, 00014, Finland; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, 02114, USA.
⁹ Abdominal Center, Department of Surgery, Helsinki University Hospital, Helsinki, 00029, Finland.
¹⁰ Department of Pathology, Central Finland Central Hospital, Jyväskylä, 40620, Finland.
¹¹ Department of Surgery, Jyväskylä Central Hospital, University of Eastern Finland, Jyväskylä, 40620, Finland.
¹² Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, 12713, Saudi Arabia.
¹³ Molecular & Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
¹⁴ Colon Cancer Genetics Group, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital, Edinburgh, EH4 2XU, UK.
¹⁵ Centre for Population Health Sciences, University of Edinburgh, Edinburgh, EH8 9AG, UK.
¹⁶ Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK.
¹⁷ CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
¹⁸ MRC Clinical Trials Unit, Aviation House, London, WC2B 6NH, UK.
¹⁹ Oxford Cancer Centre, Department of Oncology, University of Oxford, Churchill Hospital, Oxford, OX3 7LE, UK.
²⁰ Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
²¹ Department of Epidemiology, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 03756, USA.
²² Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
²³ Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Victoria, 3010, Australia; Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, 3010, Australia.
²⁴ Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, 3010, Australia.
²⁵ Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ, 85259, USA.
²⁶ Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
²⁷ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
²⁸ Department of Preventive Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
²⁹ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, USA.
³⁰ Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SW7 3RP, UK. Electronic address: richard.houlston@icr.ac.uk.

Abstract

Background: While dietary fat has been established as a risk factor for colorectal cancer (CRC), associations between fatty acids (FAs) and CRC have been inconsistent. Using Mendelian randomisation (MR), we sought to evaluate associations between polyunsaturated (PUFA), monounsaturated (MUFA) and saturated FAs (SFAs) and CRC risk.

Methods: We analysed genotype data on 9254 CRC cases and 18,386 controls of European ancestry. Externally weighted polygenic risk scores were generated and used to evaluate associations with CRC per one standard deviation increase in genetically defined plasma FA levels.

Results: Risk reduction was observed for oleic and palmitoleic MUFAs (OR_OA = 0.77, 95% CI: 0.65-0.92, P = 3.9 × 10^-3; OR_POA = 0.36, 95% CI: 0.15-0.84, P = 0.018). PUFAs linoleic and arachidonic acid had negative and positive associations with CRC respectively (OR_LA = 0.95, 95% CI: 0.93-0.98, P = 3.7 × 10^-4; OR_AA = 1.05, 95% CI: 1.02-1.07, P = 1.7 × 10^-4). The SFA stearic acid was associated with increased CRC risk (OR_SA = 1.17, 95% CI: 1.01-1.35, P = 0.041).

Conclusion: Results from our analysis are broadly consistent with a pro-inflammatory FA profile having a detrimental effect in terms of CRC risk.

Keywords: Colorectal cancer; Fatty acids; Mendelian randomisation; Plasma fatty acids; Risk.

Publication types

Meta-Analysis

MeSH terms

Biomarkers, Tumor / genetics*
Case-Control Studies
Colorectal Neoplasms / blood
Colorectal Neoplasms / ethnology
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / prevention & control
Diet / adverse effects*
Diet, Healthy
Diet, Mediterranean
Fatty Acids / adverse effects*
Fatty Acids / blood
Gene-Environment Interaction
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Inflammation Mediators / adverse effects*
Inflammation Mediators / blood
Mendelian Randomization Analysis
Odds Ratio
Phenotype
Polymorphism, Single Nucleotide*
Protective Factors
Risk Assessment
Risk Factors
Risk Reduction Behavior
White People / genetics

Substances

Biomarkers, Tumor
Fatty Acids
Inflammation Mediators

Abstract

Publication types

MeSH terms

Substances

Grants and funding