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)(+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, 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.
D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006681:HLA-D Antigens / Q000235:genetics*; D006689:Hodgkin Disease / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D017931:DNA Primers; D006681:HLA-D Antigens; D014409:Tumor Necrosis Factor-alpha