Cytokine BAFF gene variation is associated with survival of patients with T-cell lymphomas

Abstract

Purpose: Cytokine BAFF is a potent molecule for the activation and survival of B cells, and it also plays an important role in T-cell function. Genetic polymorphism (rs9514828C>T) in BAFF has been associated with elevated BAFF transcription.Wesought to determine whether rs9514828 is associated with T-cell lymphoma (TCL) survival. Experimental Design: BAFF rs9514828 genotypes and survival of TCL were analyzed in the discovery group including 150 patients, and the results were replicated in an independent validation group of 120 patients. Kaplan-Meier analysis was conducted to compare survival among different genotypes. Cox proportional hazard models were used to identify independent significant variables. Luciferase reporter gene assays were conducted to examine the function of rs9514828 variant. Results: We found that BAFF rs9514828 polymorphism was significantly associated with TCL survival. In pooled analysis of two independent groups, the favorable rs9514828 TC and TT genotypes had significantly better five-year survival rates compared with the CC genotype (47% and 53% vs. 22%, P = 2.27 × 10 -5 for log-rank test). Multivariate Cox regression analysis showed that rs9514828 was an independent prognostic factor, with HRs for patient death being 0.48 [95% confidence interval (CI), 0.32-0.71] for the CT and 0.47 (95% CI, 0.23-0.93) for the TT genotypes. Reporter gene assays indicated that the rs9514828T allele had significantly higher promoter activity than the rs9514828C counterpart. Conclusion: These findings suggest that functional polymorphism in BAFF might be a genetic determinant for the survival of patients with TCL. ©2012 AACR.