| Literature DB >> 28340513 |
Henry Rodriguez-Broadbent1, Philip J Law1, Amit Sud1, Kimmo Palin2,3, Sari Tuupanen2,3, Alexandra Gylfe2,3, Ulrika A Hänninen2,3, Tatiana Cajuso2,3, Tomas Tanskanen2,3, Johanna Kondelin2,3, Eevi Kaasinen2,3, Antti-Pekka Sarin4, Samuli Ripatti4,5,6, Johan G Eriksson7,8,9, Harri Rissanen7, Paul Knekt7, Eero Pukkala10,11, Pekka Jousilahti7, Veikko Salomaa7, Aarno Palotie4,12,13,14, Laura Renkonen-Sinisalo15, Anna Lepistö15, Jan Böhm16, Jukka-Pekka Mecklin17, Nada A Al-Tassan18, Claire Palles19, Lynn Martin19, Ella Barclay19, Susan M Farrington20, Maria N Timofeeva20, Brian F Meyer18, Salma M Wakil18, Harry Campbell21, Christopher G Smith22, Shelley Idziaszczyk22, Timothy S Maughan23, Richard Kaplan24, Rachel Kerr25, David Kerr26, Michael N Passarelli27, Jane C Figueiredo28,29, Daniel D Buchanan30,31, Aung K Win31, John L Hopper31, Mark A Jenkins31, Noralane M Lindor32, Polly A Newcomb33, Steven Gallinger34, David Conti35, Fred Schumacher35, Graham Casey36, Lauri A Aaltonen2,3, Jeremy P Cheadle22, Ian P Tomlinson19, Malcolm G Dunlop20, Richard S Houlston1.
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.Entities:
Keywords: Mendelian randomisation; cholesterol; colorectal cancer; hyperlipidaemia; risk
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Year: 2017 PMID： 28340513 PMCID： PMC6135234 DOI： 10.1002/ijc.30709
Source DB: PubMed Journal: Int J Cancer ISSN： 0020-7136 Impact factor: 7.316