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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.
Authors: Nimptsch, Katharina
Song, Mingyang
Aleksandrova, Krasimira
Katsoulis, Michail
Freisling, Heinz
Jenab, Mazda
Gunter, Marc J
Tsilidis, Konstantinos K
Weiderpass, Elisabete
Bueno-De-Mesquita, H Bas
Chong, Dawn Q
Jensen, Majken K
Wu, Chunsen
Overvad, Kim
Kühn, Tilman
Barrdahl, Myrto
Melander, Olle
Jirström, Karin
Peeters, Petra H
Sieri, Sabina
Panico, Salvatore
Cross, Amanda J
Riboli, Elio
Van Guelpen, Bethany
Myte, Robin
Huerta, José María
Rodriguez-Barranco, Miguel
Quirós, José Ramón
Dorronsoro, Miren
Tjønneland, Anne
Olsen, Anja
Travis, Ruth
Boutron-Ruault, Marie-Christine
Carbonnel, Franck
Severi, Gianluca
Bonet, Catalina
Palli, Domenico
Janke, Jürgen
Lee, Young-Ae
Boeing, Heiner
Giovannucci, Edward L
Ogino, Shuji
Fuchs, Charles S
Rimm, Eric
Wu, Kana
Chan, Andrew T
Pischon, Tobias
Keywords: ADIPOQ;Adiponectin;Colorectal cancer;Mendelian Randomization
metadata.dc.subject.mesh: Adiponectin
Aged, 80 and over
Case-Control Studies
Colorectal Neoplasms
Enzyme-Linked Immunosorbent Assay
Follow-Up Studies
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Variation
Mendelian Randomization Analysis
Middle Aged
Polymorphism, Single Nucleotide
Prospective Studies
Issue Date: 26-May-2017
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.
metadata.dc.identifier.doi: 10.1007/s10654-017-0262-y
Appears in Collections:Producción 2020

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