[The role of genetic polymorphisms within tumor necrosis factor promoter gene in non-Hodgkin's lymphomas].
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.
Juszczyński
Przemysław
P
Oddział Chorób Rozrostowych, Regionalny Ośrodek Onkologiczny, Wojewódzki Szpital Specjalistyczny im. M. Kopernika w Lodzi.
Kalinka
Ewa
E
Woszczek
Grzegorz
G
Borowiec
Maciej
M
Robak
Tadeusz
T
Kowalski
Marek L
ML
Biliński
Przemysław
P
Coiffiers
Bertrand
B
Salles
Gilles
G
Warzocha
Krzysztof
K
D000368:Aged; D000483:Alleles; D005260:Female; D006681:HLA-D Antigens / Q000235:genetics*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012016:Reference Values; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D006681:HLA-D Antigens; D014409:Tumor Necrosis Factor-alpha