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

Katharina Nimptsch, Mingyang Song, Krasimira Aleksandrova, Michail Katsoulis, Heinz Freisling, Mazda Jenab, Marc J. Gunter, Konstantinos K. Tsilidis, Elisabete Weiderpass, H. Bas Bueno-De-Mesquita, Dawn Q. Chong, Majken K. Jensen, Chunsen Wu, Kim Overvad, Tilman Kühn, Myrto Barrdahl, Olle Melander, Karin Jirström, Petra H. Peeters, Sabina SieriSalvatore Panico, Amanda J. Cross, Elio Riboli, Bethany Van Guelpen, Robin Myte, José María Huerta, Miguel Rodriguez-Barranco, José Ramón Quirós, Miren Dorronsoro, Anne Tjønneland, Anja Olsen, Ruth Travis, Marie Christine Boutron-Ruault, Franck Carbonnel, Gianluca Severi, Catalina Bonet, Domenico Palli, Jürgen Janke, Young Ae Lee, Heiner Boeing, Edward L. Giovannucci, Shuji Ogino, Charles S. Fuchs, Eric Rimm, Kana Wu, Andrew T. Chan, Tobias Pischon

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)419-430
Number of pages12
JournalEuropean Journal of Epidemiology
Volume32
Issue number5
DOIs
Publication statusPublished - May 1 2017

Keywords

  • Adiponectin
  • ADIPOQ
  • Colorectal cancer
  • Mendelian Randomization

ASJC Scopus subject areas

  • Epidemiology

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    Nimptsch, K., Song, M., Aleksandrova, K., Katsoulis, M., Freisling, H., Jenab, M., Gunter, M. J., Tsilidis, K. K., Weiderpass, E., Bueno-De-Mesquita, H. B., Chong, D. Q., Jensen, M. K., Wu, C., Overvad, K., Kühn, T., Barrdahl, M., Melander, O., Jirström, K., Peeters, P. H., ... Pischon, T. (2017). Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies. European Journal of Epidemiology, 32(5), 419-430. https://doi.org/10.1007/s10654-017-0262-y