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 PalotieLaura 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

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

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 (OROA = 0.77, 95% CI: 0.65-0.92, P = 3.9 × 10-3; ORPOA = 0.36, 95% CI: 0.15-0.84, P = 0.018). PUFAs linoleic and arachidonic acid had negative and positive associations with CRC respectively (ORLA = 0.95, 95% CI: 0.93-0.98, P = 3.7 × 10-4; ORAA = 1.05, 95% CI: 1.02-1.07, P = 1.7 × 10-4). The SFA stearic acid was associated with increased CRC risk (ORSA = 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.

Original languageEnglish
Pages (from-to)228-238
Number of pages11
JournalEuropean Journal of Cancer
Volume84
Early online date19 Aug 2017
DOIs
Publication statusPublished - Oct 2017

Keywords

  • Biomarkers, Tumor
  • Case-Control Studies
  • Colorectal Neoplasms
  • Diet
  • Diet, Mediterranean
  • European Continental Ancestry Group
  • Fatty Acids
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Healthy Diet
  • Humans
  • Inflammation Mediators
  • Mendelian Randomization Analysis
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Protective Factors
  • Risk Assessment
  • Risk Factors
  • Risk Reduction Behavior
  • Journal Article
  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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