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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

Nimptsch, Katharina; Song, Mingyang; Aleksandrova, Krasimira; Katsoulis, Michail; Freisling, Heinz; Jenab, Mazda; Gunter, Marc J; Tsilidis, Konstantinos K; Weiderpass, Elisabete and Bueno-De-Mesquita, Bas H., et al. (2017) In European Journal of Epidemiology p.1-12
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... (More)

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.

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Adiponectin, ADIPOQ, Colorectal cancer, Mendelian Randomization
in
European Journal of Epidemiology
pages
12 pages
publisher
Springer
external identifiers
  • scopus:85019730130
  • wos:000405184200008
ISSN
0393-2990
DOI
10.1007/s10654-017-0262-y
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English
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yes
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6febbb2a-f866-4b84-825e-c51f20565a25
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2017-06-21 16:17:36
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2017-09-21 03:00:03
@article{6febbb2a-f866-4b84-825e-c51f20565a25,
  abstract     = {<p>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.</p>},
  author       = {Nimptsch, Katharina and Song, Mingyang and Aleksandrova, Krasimira and Katsoulis, Michail and Freisling, Heinz and Jenab, Mazda and Gunter, Marc J and Tsilidis, Konstantinos K and Weiderpass, Elisabete and Bueno-De-Mesquita, Bas H. and Chong, Dawn Q. and Jensen, Majken K. and Wu, Chunsen and Overvad, Kim and Kühn, Tilman and Barrdahl, Myrto and Melander, Olle and Jirström, Karin and Peeters, Petra H and Sieri, Sabina and Panico, Salvatore and Cross, Amanda J and Riboli, Elio and Van Guelpen, Bethany and Myte, Robin and Huerta, José María and Rodriguez-Barranco, Miguel and Quirós, José Ramón and Dorronsoro,, Miren and Tjønneland, Anne and Olsen, Anja and Travis, Ruth and Boutron-Ruault,, Marie-Christine and Carbonnel, Franck and Severi, Gianluca and Bonet, Catalina and Palli, Domenico and Janke, Jürgen and Lee, Young-Ae and Boeing, Heiner and Giovannucci, Edward L. and Ogino, Shuji and Fuchs, Charles S. and Rimm, Eric and Wu, Kana and Chan, Andrew T. and Pischon, Tobias},
  issn         = {0393-2990},
  keyword      = {Adiponectin,ADIPOQ,Colorectal cancer,Mendelian Randomization},
  language     = {eng},
  month        = {05},
  pages        = {1--12},
  publisher    = {Springer},
  series       = {European Journal of Epidemiology},
  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},
  url          = {http://dx.doi.org/10.1007/s10654-017-0262-y},
  year         = {2017},
}