Human leukocyte antigens class II and tumor necrosis factor genetic polymorphisms are independent predictors of non-Hodgkin lymphoma outcome

Abstract

Tumor necrosis factor (TNF) production and non-Hodgkin lymphoma (NHL) outcome was found to be related to the TNF−308polymorphism. To explore whether this could be linked to neighboring polymorphisms, we genotyped the TNF−376,−308,−238,−163, lymphotoxin alpha (LTα)+252, and HLA DRB1 alleles in 204 patients with NHL and 120 controls. TNF−308A was the only allele associated with higher TNF and its p55 and p75 receptors' levels (P = .009, P = .03, andP = .007) and lower complete remission rates (P = .006). Freedom from progression (FFP) and overall survival (OS) were shorter in patients with TNF−308A(P = .009 and P = .02), null HLA DRB1*02 allele (P = .007 and P = .14), or both genetic markers (P = .004 and P = .005). Multivariate analysis incorporating International Prognostic Index (IPI) identified TNF−308A (P < .0001, relative risk [RR] = 1.63; P < .0001, RR = 1.51) and null HLA DRB1*02 alleles (P = .015, RR = 1.18;P < .0001, RR = 1.25) as independent factors for FFP and OS. These results indicate the existence of at least 2 inherited factors involved in NHL outcome.