Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis.
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Date
2017-10-01Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Colorectal Neoplasms
Genetic Predisposition to Disease
Fatty Acids
Inflammation Mediators
Diet
Odds Ratio
Risk Assessment
Risk Factors
Case-Control Studies
Risk Reduction Behavior
Diet, Mediterranean
Phenotype
Polymorphism, Single Nucleotide
European Continental Ancestry Group
Genome-Wide Association Study
Mendelian Randomization Analysis
Gene-Environment Interaction
Protective Factors
Biomarkers, Tumor
Diet, Healthy
Research team
Cancer Genomics
Molecular & Population Genetics
Language
eng
Date accepted
2017-07-22
License start date
2017-10
Citation
European journal of cancer (Oxford, England : 1990), 2017, 84 pp. 228 - 238
Publisher
ELSEVIER SCI LTD