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¹ Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
² Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic
³ Department of Biology, University of Pisa, via Derna, Pisa 56127, Italy
⁴ National Institute of Public Health, Centre of Occupational Health, Srobarova, 100 42 Prague 10, Czech Republic
⁵ Department of Oncology, General Teaching Hospital, U Nemocnice 2, 128 08 Prague 2, Czech Republic
⁶ Karolinska Institute, Center for Family and Community Medicine, Alfred Nobels allé 12, 14183 Huddinge, Sweden

(Correspondence should be addressed to A Försti; Email: a.foersti{at}dkfz-heidelberg.de)

Western lifestyle leading to obesity and type 2 diabetes has been associated with increased risk of colorectal cancer (CRC). Diet and related factors may affect the risk by modifying plasma insulin levels. Thus, the inter-individual variation in insulin signaling may play a plausible role in the development of CRC. We hypothesized that functional polymorphisms in the insulin pathway genes INS, INSR, IGFBPI, insulin receptor substrate 1 (IRS1), and IRS2 may be associated with CRC. We studied the association of five single nucleotide polymorphisms (SNPs) with the risk of CRC using a hospital-based case–control design with 712 cases and 748 controls from the Czech Republic. The INSR A-603G promoter SNP, which is located within a known Sp1-binding site, was associated with the risk of CRC, with carriers of the G allele having a decreased risk (odds ratios (OR) 0.71, 95% confidence interval (CI) 0.54–0.93). Carrying the variant allele of the IRS1 Gly972Arg SNP further decreased the risk among the INSR-603G allele carriers (OR 0.28, 95% CI 0.11–0.70). SNPs in the INS, IGFBPI, and IRS2 genes did not affect the risk of CRC. In conclusion, genetic variation in the insulin signaling pathway genes may affect the risk of CRC.

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				S. Pechlivanis, J. L. Bermejo, B. Pardini, A. Naccarati, L. Vodickova, J. Novotny, K. Hemminki, P. Vodicka, and A. Forsti Genetic variation in adipokine genes and risk of colorectal cancer Eur. J. Endocrinol., June 1, 2009; 160(6): 933 - 940. [Abstract] [Full Text] [PDF]