TNFα gene/protein in tumorigenesis of sporadic colon adenocarcinoma.

Purpose: Inherited polymorphisms in immunomodulatory genes such as cytokines may contribute to variation in immunological response and genetic susceptibility for complex diseases, including cancer. TNFα can mediate tumor progression by inducing proliferation, invasion and metastasis of tumor cells. The aim of our study was to examine the allelic frequencies of TNFα promoter SNPs, -1031 T/C, -857 C/T, -308 G/A and -238 G/A, in patients with sporadic colon adenocarcinoma in order to investigate the possible role of these SNPs in susceptibility to sporadic colon cancer. Another aim of this study was to examine the influence of TNFα SNPs on TNFα mRNA and protein expression in colon tumors and their possible role in the development and progression of this type of tumor.

Results: The distribution of all four TNFα SNP genotypes in patients showed no significant difference compared to controls. No statistically significant difference in TNFα mRNA expression in tumors and corresponding normal mucous tissue was found (p=0.14). A statistically significant (p=0.028) difference was found in TNFα mRNA expression between histological grade 1 and histological grade 2 and 3 tumors. Additionally, a statistically significant correlation (p=0.03) was found between TNFα-857 C/T genotypes and TNFα mRNA expression in tumor tissue. TNFα mRNA expression was significantly higher in the tumor tissue of patients with -857 CT and -857 TT genotypes. Most of the tumors (78.26%) were positive for TNFα protein. No correlation was found between the TNFα protein expression and clinicopathological characteristics as well as TNFα genotypes. However, patients with TNFα protein negative tumors had longer survival but the result was not statistically significant (p=0.365).

Conclusion: Our results suggest the role of TNFα as one of the immunomodulatory genes in the progression of sporadic colon cancer.