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

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

The Institute of Cancer Research
University of Helsinki
National Institute for Health and Welfare
Folkhalsan
Helsinki University Central Hospital
Finnish Cancer Registry
Tampere University
Wellcome Trust
Massachusetts General Hospital
Broad Institute
Central Finland Central Hospital
University of Eastern Finland
King Faisal Specialist Hospital and Research Centre
University of Oxford
University of Edinburgh
Cardiff University
Medical Research Council
Cedars-Sinai Medical Center
University of Southern California
University of Melbourne
Mayo Clinic Scottsdale-Phoenix, Arizona
Fred Hutchinson Cancer Research Center
University of Toronto
University of Virginia

Research output: Contribution to journal › Article › peer-review

95 Scopus citations

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.

Original language	English
Pages (from-to)	228-238
Number of pages	11
Journal	European Journal of Cancer
Volume	84
DOIs	https://doi.org/10.1016/j.ejca.2017.07.034
State	Published - Oct 2017

Keywords

Colorectal cancer
Fatty acids
Mendelian randomisation
Plasma fatty acids
Risk

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10.1016/j.ejca.2017.07.034

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May-Wilson, S., Sud, A., Law, P. J., Palin, K., Tuupanen, S., Gylfe, A., Hänninen, U. A., Cajuso, T., Tanskanen, T., Kondelin, J., Kaasinen, E., Sarin, A. P., Eriksson, J. G., Rissanen, H., Knekt, P., Pukkala, E., Jousilahti, P., Salomaa, V., Ripatti, S., ... Houlston, R. S. (2017). Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis. European Journal of Cancer, 84, 228-238. https://doi.org/10.1016/j.ejca.2017.07.034

@article{dc432f0e373e4ac998f60908553636f6,

title = "Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis",

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.",

keywords = "Colorectal cancer, Fatty acids, Mendelian randomisation, Plasma fatty acids, Risk",

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

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = oct,

doi = "10.1016/j.ejca.2017.07.034",

language = "English",

volume = "84",

pages = "228--238",

journal = "European Journal of Cancer",

issn = "0959-8049",

}

May-Wilson, S, Sud, A, Law, PJ, Palin, K, Tuupanen, S, Gylfe, A, Hänninen, UA, Cajuso, T, Tanskanen, T, Kondelin, J, Kaasinen, E, Sarin, AP, Eriksson, JG, Rissanen, H, Knekt, P, Pukkala, E, Jousilahti, P, Salomaa, V, Ripatti, S, Palotie, A, Renkonen-Sinisalo, L, Lepistö, A, Böhm, J, Mecklin, JP, Al-Tassan, NA, Palles, C, Farrington, SM, Timofeeva, MN, Meyer, BF, Wakil, SM, Campbell, H, Smith, CG, Idziaszczyk, S, Maughan, TS, Fisher, D, Kerr, R, Kerr, D, Passarelli, MN, Figueiredo, JC, Buchanan, DD, Win, AK, Hopper, JL, Jenkins, MA, Lindor, NM, Newcomb, PA, Gallinger, S, Conti, D, Schumacher, F, Casey, G, Aaltonen, LA, Cheadle, JP, Tomlinson, IP, Dunlop, MG & Houlston, RS 2017, 'Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis', European Journal of Cancer, vol. 84, pp. 228-238. https://doi.org/10.1016/j.ejca.2017.07.034

TY - JOUR

T1 - Pro-inflammatory fatty acid profile and colorectal cancer risk

T2 - A Mendelian randomisation analysis

AU - May-Wilson, Sebastian

AU - Sud, Amit

AU - Law, Philip J.

AU - Palin, Kimmo

AU - Tuupanen, Sari

AU - Gylfe, Alexandra

AU - Hänninen, Ulrika A.

AU - Cajuso, Tatiana

AU - Tanskanen, Tomas

AU - Kondelin, Johanna

AU - Kaasinen, Eevi

AU - Sarin, Antti Pekka

AU - Eriksson, Johan G.

AU - Rissanen, Harri

AU - Knekt, Paul

AU - Pukkala, Eero

AU - Jousilahti, Pekka

AU - Salomaa, Veikko

AU - Ripatti, Samuli

AU - Palotie, Aarno

AU - Renkonen-Sinisalo, Laura

AU - Lepistö, Anna

AU - Böhm, Jan

AU - Mecklin, Jukka Pekka

AU - Al-Tassan, Nada A.

AU - Palles, Claire

AU - Farrington, Susan M.

AU - Timofeeva, Maria N.

AU - Meyer, Brian F.

AU - Wakil, Salma M.

AU - Campbell, Harry

AU - Smith, Christopher G.

AU - Idziaszczyk, Shelley

AU - Maughan, Timothy S.

AU - Fisher, David

AU - Kerr, Rachel

AU - Kerr, David

AU - Passarelli, Michael N.

AU - Figueiredo, Jane C.

AU - Buchanan, Daniel D.

AU - Win, Aung K.

AU - Hopper, John L.

AU - Jenkins, Mark A.

AU - Lindor, Noralane M.

AU - Newcomb, Polly A.

AU - Gallinger, Steven

AU - Conti, David

AU - Schumacher, Fred

AU - Casey, Graham

AU - Aaltonen, Lauri A.

AU - Cheadle, Jeremy P.

AU - Tomlinson, Ian P.

AU - Dunlop, Malcolm G.

AU - Houlston, Richard S.

PY - 2017/10

Y1 - 2017/10

N2 - 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.

AB - 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.

KW - Colorectal cancer

KW - Fatty acids

KW - Mendelian randomisation

KW - Plasma fatty acids

KW - Risk

UR - https://www.scopus.com/pages/publications/85027680152

U2 - 10.1016/j.ejca.2017.07.034

DO - 10.1016/j.ejca.2017.07.034

M3 - Article

C2 - 28829991

AN - SCOPUS:85027680152

SN - 0959-8049

VL - 84

SP - 228

EP - 238

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

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

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Keywords

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