Journal
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
Volume 42, Issue 5, Pages 628-632Publisher
TAYLOR & FRANCIS AS
DOI: 10.1080/00365520601106699
Keywords
disease expression; HNPCC; immune response; SNPs
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Objective. Hereditary non-polyposis colorectal cancer (HNPCC) is caused by germline mutations in DNA mismatch repair (MMR) genes and is characterized by familial aggregations of early-onset epithelial cancers. Inflammatory cells produce an attractive environment for tumour growth since reactive oxygen and nitrogen species generated by inflammatory cytokine induction can cause damage to DNA and proteins. In this study the objective was to investigate single nucleotide polymorphisms (SNPs) in cytokine genes to assess their impact on disease expression in individuals diagnosed with HNPCC. Material and methods. DNA samples from 220 participants diagnosed with HNPCC were genotyped for SNPs in IL-6, IL-1 beta, TNF-alpha, IFN-gamma, IL-10, IL-4 and IL-1RN. The association between the polymorphisms and disease characteristics, i. e. affected or unaffected with colorectal cancer (CRC) and age of diagnosis of CRC, was tested with the Pearson chi(2) test and by Kaplan-Meier survival analysis. Results. There was no significant difference between CRC patients and unaffected MMR gene mutation carriers for any of the SNPs studied and the Kaplan-Meier survival analysis showed no significant difference between age of diagnosis of CRC and genotype. Conclusions. The SNPs selected for this study do not appear to modify disease expression in HNPCC. Given the complexity of the inflammatory response, the limited number of SNPs studied does not rule out the notion that other cytokine polymorphisms could act as disease modifiers of disease expression in HNPCC.
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