Citations 2
Lack of association between modifiable exposures and glioma risk: A Mendelian randomisation analysis
Saunders, Charlie N. , Cornish, Alex J. , Kinnersley, Ben , Claus, Elizabeth B. , Schildkraut, Joellen M. , Barnholtz‐Sloan, Jill S. , Bernstein, Jonine L. , Lai, Rose , Rajaraman, Preetha , Johansen, Christoffer , Jenkins, Robert B. , Melin, Beatrice , Wrensch, Margaret , Sanson, Marc , Bondy, Melissa L. , Houlston, Richard S. , Houlston, Richard S , Barnholtz-Sloan, Jill S , Sanson, Marc , Law, Philip , Il’yasova, Dora , Olson, Sara H. , Chanock, Stephen Jacob
Neuro-Oncology | October 23, 2019 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Background The etiological basis of glioma is poorly understood. We have used genetic markers in a Mendelian Randomisation (MR) framework to examine if lifestyle, cardiometabolic and inflammatory factors influence the risk of glioma. This methodology reduces bias from confounding and is not affected by reverse causation. Methods We identified genetic instruments for 37 potentially modifiable risk factors and evaluated their association with glioma risk using data from a genome-wide association study of 12,488 glioma patients and 18,169 controls. We used the estimated odds ratio of glioma associated with each of the genetically defined traits to infer evidence for a causal relationship with the following exposures: lifestyle and dietary factors (height, plasma IGF-1, blood carnitine, blood methionine, blood selenium, blood zinc, circulating adiponectin, circulating carotenoids, iron status, serum calcium, vitamin [A1, B12, B6, E and 25-hydroxyvitamin D], fatty acids levels [mono-unsaturated, omega-3 and omega-6] and circulating fetuin-A); cardiometabolic factors (birth weight, HDL cholesterol, LDL cholesterol, total cholesterol, total triglycerides, basal metabolic rate, body fat percentage, body mass index, fasting glucose, fasting proinsulin, HbA1C levels, diastolic and systolic blood pressure, waist circumference, waist-to-hip ratio) were included; inflammatory factors (C-reactive protein (CRP), plasma IL-6 sRa and serum IgE). Results After correction for the testing of multiple potential risk factors and excluding associations driven by one single nucleotide polymorphism (SNP) no significant association with glioma risk was observed (i.e. PCorrected > 0.05). Conclusions This study did not provide evidence supporting any of the 37 factors examined as having a significant influence on glioma risk.
Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer
Rodriguez‐Broadbent, Henry , Law, Philip , Sud, Amit , Palin, Kimmo , Tuupanen, Sari, Gylfe, Alexandra E., Hänninen, Ulrika A. , Cajuso, Tatiana , Tanskanen, Tomas , Kondelin, Johanna , Kaasinen, Eevi , Sarin, Antti‐Pekka , Rissanen, Harri , Knekt, Paul , Jousilahti, Pekka , Palotie, Aarno , Renkonen‐Sinisalo, Laura , Lepistö, Anna , Böhm, Jan , Mecklin, Jukka‐Pekka , Tassan, Nada Al , Palles, Claire , Martin, Lynn , Barclay, Ella, Farrington, Susan M. , Timofeeva, Maria , Wakil, Salma M. , Campbell, Harry , Idziaszczyk, Shelley, Kaplan, Richard , Kerr, Rachel , Kerr, David , Passarelli, Michael N. , Figueiredo, Jane C. , Buchanan, Daniel D. , Win, Aung Ko , Jenkins, Mark A. , Lindor, Noralane M. , Gallinger, Steven , Conti, David V. , Schumacher, Fredrick R. , Casey, Graham , Aaltonen, Lauri A. , Cheadle, Jeremy P. , Tomlinson, Ian , Dunlop, Malcolm G. , Houlston, Richard S. , Law, Philip J , Buchanan, Daniel D , Win, Aung K , Ripatti, Samuli , Eriksson, Johan G. , Pukkala, Eero , Salomaa, Veikko , Palotie, Aarno V. , Meyer, Brian F. , Smith, Christopher G. , Maughan, Tim , Hopper, John L. , Newcomb, Polly A. , Houlston, Richard S , Jenkins, Mark A , Kaplan, Richard , Kerr, Rachel , Palles, Claire , Conti, David V
International Journal of Cancer | March 25, 2017 | Volume: 140 | Issue: 12 | Pages: 2701-2708
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.