title: Colorectal cancer severity and survival in correlation with tumour necrosis factor-alpha.
abstract: Colorectal cancer (CRC) development is strongly associated with innate immune mechanisms and intestinal inflammation. The aim of the study was to investigate the pre-operative serum levels of TNF-α and its correlation with cancer progression and survival in CRC patients taking into account the genotype of -308G/A promoter polymorphism in TNF-α gene (rs1800629). TNF-α -308G/A genotypes of 119 CRC cases and 177 no CRC controls were determined by restriction fragment length polymorphism assay (RFLP-PCR). TNF-α serum levels were measured by enzyme-linked immunosorbent assay (ELISA). Although no significant differences in allele and genotype frequencies between CRC and controls were observed, it should be noted that the minor allele-A and its homozygous genotype were overrepresented among CRC. In addition, allele-A was more frequent in early CRC patients compared to advanced cases. TNF-α serum level was significantly higher in CRC patients than in controls (36.1 ± 8.4 pg/mL vs. 18.66 ± 11 pg/mL;p= 0.0000001). In the subgroup analysis by tumour-node-metastasis stages, the highest TNF-α level was found in stage IV (42.7 ± 12.5 pg/mL) and was significantly elevated compared to earlier stages of CRC and controls. The survival rate of CRC patients with low TNF-α serum level, estimated as median survival, was significantly higher than that of patients with high levels of TNF-α (38.4 vs. 7.761 months; log rank testp= 0.00015) In conclusion, we can affirm that TNF-α affects tumour development along with disease progression which has an impact on the survival of CRC.
authors.affiliation: Department of Neurosurgery, Surgery and Urology, University Hospital, Trakia University , Stara Zagora , Bulgaria ; Department of Colorectal Surgery, Milton Keynes Hospital , Milton Keynes , UK.
authors.forename: Noyko
authors.initials: N
authors.lastname: Stanilov
authors.affiliation: Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University , Stara Zagora , Bulgaria.
authors.forename: Lyuba
authors.initials: L
authors.lastname: Miteva
authors.affiliation: Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University , Stara Zagora , Bulgaria.
authors.forename: Zlatka
authors.initials: Z
authors.lastname: Dobreva
authors.affiliation: Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University , Stara Zagora , Bulgaria.
authors.forename: Spaska
authors.initials: S
authors.lastname: Stanilova
keywords: cytokine production; inflammation; single nucleotide polymorphism; tumour progression