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 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

Cancer and Genomic Sciences

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	228-238
Number of pages	11
Journal	European Journal of Cancer
Volume	84
Early online date	19 Aug 2017
DOIs	https://doi.org/10.1016/j.ejca.2017.07.034
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ejca.2017.07.034Licence: Creative Commons: Attribution (CC BY)

Cite this

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{31569acf29a3472588f2ff9a02da4761,

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 = "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",

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 Antti-Pekka Sarin 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 Jukka-Pekka Mecklin 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}",

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",

publisher = "Elsevier",

}

May-Wilson, S, Sud, A, Law, PJ, Palin, K, Tuupanen, S, Gylfe, A, Hänninen, UA, Cajuso, T, Tanskanen, T, Kondelin, J, Kaasinen, E, Sarin, A-P, Eriksson, JG, Rissanen, H, Knekt, P, Pukkala, E, Jousilahti, P, Salomaa, V, Ripatti, S, Palotie, A, Renkonen-Sinisalo, L, Lepistö, A, Böhm, J, Mecklin, J-P, 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 - Biomarkers, Tumor

KW - Case-Control Studies

KW - Colorectal Neoplasms

KW - Diet

KW - Diet, Mediterranean

KW - European Continental Ancestry Group

KW - Fatty Acids

KW - Gene-Environment Interaction

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Healthy Diet

KW - Humans

KW - Inflammation Mediators

KW - Mendelian Randomization Analysis

KW - Odds Ratio

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Protective Factors

KW - Risk Assessment

KW - Risk Factors

KW - Risk Reduction Behavior

KW - Journal Article

KW - Meta-Analysis

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ejca.2017.07.034

DO - 10.1016/j.ejca.2017.07.034

M3 - Article

C2 - 28829991

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

Abstract

Keywords

UN SDGs

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