Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer.
View/ Open
Date
2017-06-15Author
Rodriguez-Broadbent, H
Law, PJ
Sud, A
Palin, K
Tuupanen, S
Gylfe, A
Hänninen, UA
Cajuso, T
Tanskanen, T
Kondelin, J
Kaasinen, E
Sarin, A-P
Ripatti, S
Eriksson, JG
Rissanen, H
Knekt, P
Pukkala, E
Jousilahti, P
Salomaa, V
Palotie, A
Renkonen-Sinisalo, L
Lepistö, A
Böhm, J
Mecklin, J-P
Al-Tassan, NA
Palles, C
Martin, L
Barclay, E
Farrington, SM
Timofeeva, MN
Meyer, BF
Wakil, SM
Campbell, H
Smith, CG
Idziaszczyk, S
Maughan, TS
Kaplan, R
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
While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP-CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20-1.79, p = 1.68 × 10-4 ). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92-1.18, p = 0.49), 0.94 (95% CI: 0.84-1.05, p = 0.27), and 0.98 (95% CI: 0.85-1.12, p = 0.75) respectively. A genetic risk score for 3-hydoxy-3-methylglutaryl-coenzyme A reductase (HMGCR) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR = 0.69, 95% CI: 0.49-0.99, p = 0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia.
Collections
Subject
Humans
Colorectal Neoplasms
Genetic Predisposition to Disease
Cholesterol
Triglycerides
Lipoproteins, HDL
Lipoproteins, LDL
Logistic Models
Odds Ratio
Risk Assessment
Risk Factors
Polymorphism, Single Nucleotide
Hyperlipidemias
Genome-Wide Association Study
Mendelian Randomization Analysis
Research team
Cancer Genomics
Language
eng
Date accepted
2017-02-08
License start date
2017-06
Citation
International journal of cancer, 2017, 140 (12), pp. 2701 - 2708
Publisher
WILEY