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

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): 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
BackgroundWhile 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.MethodsWe 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.ResultsRisk 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).ConclusionResults from our analysis are broadly consistent with a pro-inflammatory FA profile having a detrimental effect in terms of CRC risk.



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