Genetic Polymorphism And Protein Expression Of Molecular Markers In Apoptotic Pathways In T-cell Lymphoma

Part 1 Asix-nucleotide insertion-deletion polymorphism in the CASP8 promoter and susceptibility to T-cell lymphomaIn the present study, we assessed the role of genetic polymorphisms in CASP8 in the risk of T-cell lymphoma. Genotypes of CASP8 were determined by PCR-RFLP in 92 patients with T-cell lymphoma and 301 frequency-matched controls. The association between genotypes and risk of T-cell lymphoma was estimated by odds ratio(OR), and the 95% confidence intervals(CI) calculated by unconditional logistic regression.It was found that subjects with the CASP8 -652 6N ins/del genotype were at an increased risk for T-cell lymphoma(OR 1.93; 95% CI 1.13-3.31) compared with those with CASP8 -652 6N ins/ins genotype. It was observed that subjects having the -652 6N del/del genotype were at a 7.42-fold (95% CI 3.13-17.62) increased risk for T-cell lymphoma compared with those having the CASP8 -652 6N ins/ins genotype. We also investigated the association between genetic polymorphisms in CASP8 and B-cell lymphoma but no association was found.These data suggest that a six-nucleotide deletion (-652 6N del) variant in the CASP8 promoter is associated with increased risk of T-cell lymphoma.Part 2 Genetic polymorphism in CASP8 and expression of Caspase-8 and BCL-2 in peripheral T-cell lymphomaThe expression of Caspase-8,BCL-2 in 44 cases with peripheral T-cell lymphoma was examined with immunohistochemistry and the relationship between protein expression and clinical characteristics was analyzed. The relationship between the polymorphism in CASP8 and clinical factors of the disease was also explored. Cases with a negative or weak positive expression of Caspase-8 showed a higher frequency of B symptoms and fever. BCL-2 expression was associated with a higher prognostic index for PTCL-U. Cases with CASP8 -652 6N del/del genotype had a higher stageâ…£disease rate than those with ins/del or ins/inso In patients with -652 6N del/del genotype, the positive rate of Caspase-8 was lower than in those with ins/del or ins/ins, with marginal significance (P=0.064).The data suggest that BCL-2 expression in peripheral T-cell lymphoma may confer a poor prognosis, and CASP8 -652 6N del/del genotype and its functional change may have a role in the development of the disease.