Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer.
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ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2017-06-15
Date Accepted
2017-02-08
Abstract
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.
Citation
International journal of cancer, 2017, 140 (12), pp. 2701 - 2708
Source Title
Publisher
WILEY
ISSN
0020-7136
eISSN
1097-0215
Collections
Research Team
Cancer Genomics