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Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer

2017; Wiley; Volume: 140; Issue: 12 Linguagem: Inglês

10.1002/ijc.30709

1097-0215

Henry Rodriguez‐Broadbent, Philip Law, Amit Sud, Kimmo Palin, Sari Tuupanen, Alexandra E. Gylfe, Ulrika A. Hänninen, Tatiana Cajuso, Tomas Tanskanen, Johanna Kondelin, Eevi Kaasinen, Antti‐Pekka Sarin, Samuli Ripatti, Johan G. Eriksson, Harri Rissanen, Paul Knekt, ­Eero Pukkala, Pekka Jousilahti, Veikko Salomaa, Aarno Palotie, Laura Renkonen‐Sinisalo, Anna Lepistö, Jan Böhm, Jukka‐Pekka Mecklin, Nada Al Tassan, Claire Palles, Lynn Martin, Ella Barclay, Susan M. Farrington, Maria Timofeeva, Brian F. Meyer, Salma M. Wakil, Harry Campbell, Christopher G. Smith, Shelley Idziaszczyk, Tim Maughan, Richard Kaplan, Rachel Kerr, David Kerr, Michael N. Passarelli, Jane C. Figueiredo, Daniel D. Buchanan, Aung Ko Win, John L. Hopper, Mark A. Jenkins, Noralane M. Lindor, Polly A. Newcomb, Steven Gallinger, David V. Conti, Fredrick R. Schumacher, Graham Casey, Lauri A. Aaltonen, Jeremy P. Cheadle, Ian Tomlinson, Malcolm G. Dunlop, Richard S. Houlston,

Genetic Associations and Epidemiology

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.