Search

Elevated tumor necrosis factor (TNF) and its soluble receptors (p55 and p75) plasma levels in patients with non-Hodgkin's lymphoma (NHL) have been shown to correlate with various adverse prognostic factors and predict poor NHL outcome. In vitro studies demonstrated that TNF expression level could be influenced by TNF-376, -308, -238, -163 promoters' polymorphisms. To explore whether these polymorphisms confer the susceptibility to and influence NHL outcome, we genotyped the TNF-376, -308, -238, -163 polymorphisms in 204 NHL patients and 96 healthy controls. The frequency and distribution of polymorphic alleles were similar in both studied groups. TNF-308A was the only polymorphic allele related to elevated TNF, p55, p75 plasma levels (p = 0.009, p = 0.03, p = 0.007, respectively), lower complete remission rate (p = 0.01), higher progression (p = 0.06) and death (p = 0.01) incidences. TNF-308A was the sole allele of independent prognostic significance for shorter freedom from progression (FFP) and overall survival (OS) (p = 0.009 and p = 0.017, respectively). These data indicate that innate immunity as reflected by the genetic propensity of the host to regulate TNF expression influences clinical course and outcome of NHL.