Genetic variation in adipokine genes and risk of colorectal cancer

Objective: Obesity has been related to an increased risk of colorectal cancer (CRC). Adipokines produced by the adipose tissue are directly linked to obesity and may thus contribute to the pathogenesis of CRC. We hypothesized that potentially functional polymorphisms in the adipokine genes leptin (LEP), leptin receptor (LEPR), resistin (RETN). and adiponectin (ADIPOQ) may be associated with CRC. Design and methods: We studied the association of four putatively functional single nuclecitide polyworphisms (SNPs) with CRC risk using a hospital-based study design with 702 cases and 752 controls from the Czech Republic. We used likelihood ratio tests to select the best model to represnt the relationship between genotypes and risk of CRC. Age-adjusted odds ratios (ORS) under the best model were calculated for each SNP Previous genotyping data on insulin (INS)-related genes were used to explore interactions between genes in obesity- and diabetes-related pathways by using two independent methods, logistic regression, and multifactor-dimensionality reduction. Results: A trend to associate between the RETN SNP rs1862513 (C-420G) and CRC risk was observed (per allele OR 1.18. 95% confidence interval (0.99-1.40). Statistically, significant interactions were observed between the INS SNP rs3842754 (+1.1271NSPstl) genotypes and both the LEPR SNP, rs1137101 (Q223R) and the ADIPOQ SNP rs266729 (C-11374G) genotypes. Conclusions: Our results Suggest that variants in the adipokine genes may affect CRC risk in combination with variants in diabetes-related genes.