Genetic Polymorphisms In CASP8, Fas And Fas Ligand And The Risk Of Peripheral T-cell Lymphoma And The Relationship Between The Genetic Polymerphisms And The Clinical Characteristics And Prognosis

Genetic polymorphisms in CASP8, Fas and Fas ligand and the risk of peripheral T-cell lymphoma and the relationship between the genetic polymorphisms and the clinical characteristics and prognosisFas-Fas ligand (FasL)-mediated cell apoptosis is a classic pathway of the immune cells death and is important for the immune homeostasis, if the function of the fas/fasL is impaired, which will result in disease, including carcinogenesis. Therefore this study examined the association between functional variants of Fas (-1377G>A and-670A>G), FasL (-844T>C), and caspase-8 (CASP8) six-nucleotide deletion polymorphism (-6526N ins-del) and risk of peripheral T-cell lymphoma(PTCL),also explored the relationship between the genetic polymorphisms in Fas and CASP8 and the clinical characteristics and prognosis. Genotypes of Fas, FasL and CASP8 were determined in 100 patients with PTCL and 544 frequency-matched controls. Odds ratios (OR) and 95%confidence intervals (95%CI) were estimated by logistic regression, and all statistical tests were two sided, p value must be less than 0.05.We found a significant correlation in risk of PTCL with Fas and CASP8 but not FasL polymorphisms. Compared with those with Fas-1377GG, the subjects with Fas-1377AA had a decreased risk for PTCL, OR=0.48(95%CI 0.23-0.99, p=0.049); Compared with those with the CASP8-6526N ins/ins genotype, the subjects with CASP8-6526N ins/del had an increased risk for T-cell lymphoma, OR=1.84 (95%CI 1.18-2.87, p=0.007). The genetic polymorphisms in Fas-670 A>G and FasL-844T> C had no correlationship with the risk of PTCL. We also investigated the association between genetic polymorphisms in Fas, FasL and CASP8 and B-cell lymphoma. We found that a significant correlation in risk of B-cell lymphoma with Fas and FasL but not CASP8 polymorphisms.Compared with those with Fas-1377GG, the subjects with Fas-1377GA had a decreased risk for B-cell lymphoma, OR=0.57 (95%CI 0.41-0.77, p<0.001); Compared with those with the FasL-844CC genotype, the subjects with FasL-844CT had an increased risk for B-cell lymphoma, OR=1.37 (95%CI 1.01-1.90, p=0.043). The genetic polymorphisms in Fas-670 A>G and CASP8-6526N ins/del had no correlationship with the risk of B-cell lymphoma. These data suggest that CASP8-6526N ins/del is associated with increased risk of PTCL, The FasL-844CT is associated with increased risk of B-cell lymphoma, and the Fas-1377GA and Fas-1377AA is a protective factor for B-cell lymphoma and PTCL respectively. Based on the relationship between the risk of PTCL and the genetic polymorphisms in Fas, FasL and CASP8. We further expored the the relationship between the genetic polymorphisms in Fas and CASP8 and the clinical characteristics and prognosis. Except that the CASP8-6526N ins/del genotype is more often in male than female (p=0.032),we couldn't find any subjects with relationship between the the genetic polymorphisms in Fas and CASP8 and the clinical characteristics and prognosis.We need a large number patients to find the true relationship of them.