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

Tumor necrosis factor (TNF) production and non-Hodgkin lymphoma (NHL) outcome was found to be related to the TNF-308 polymorphism. To explore whether this could be linked to neighboring polymorphisms, we genotyped the TNF-376,-308,-238,-163, lymphotoxin alpha (LTalpha)1252, 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, and P=.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.