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Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies

Item Type:Article
Title:Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies
Creators Name:Nimptsch, K. and Song, M. and Aleksandrova, K. and Katsoulis, M. and Freisling, H. and Jenab, M. and Gunter, M.J. and Tsilidis, K.K. and Weiderpass, E. and Bueno-De-Mesquita, H.B. and Chong, D.Q. and Jensen, M.K. and Wu, C. and Overvad, K. and Kühn, T. and Barrdahl, M. and Melander, O. and Jirstrom, K. and Peeters, P.H. and Sieri, S. and Panico, S. and Cross, A.J. and Riboli, E. and Van Guelpen, B. and Myte, R. and Huerta, J.M. and Rodriguez-Barranco, M. and Quirós, J.R. and Dorronsoro, M. and Tjønneland, A. and Olsen, A. and Travis, R. and Boutron-Ruault, M.C. and Carbonnel, F. and Severi, G. and Bonet, C. and Palli, D. and Janke, J. and Lee, Y.A. and Boeing, H. and Giovannucci, E.L. and Ogino, S. and Fuchs, C.S. and Rimm, E. and Wu, K. and Chan, A.T. and Pischon, T.
Abstract:Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer.
Keywords:Adiponectin, ADIPOQ, Colorectal Cancer, Mendelian Randomization
Source:European Journal of Epidemiology
ISSN:0393-2990
Publisher:Springer (Germany)
Volume:32
Number:5
Page Range:419-430
Date:May 2017
Official Publication:https://doi.org/10.1007/s10654-017-0262-y
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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