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Prepublished online as a Blood First Edition Paper on June 7, 2002; DOI 10.1182/blood-2002-02-0654.
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Blood, 15 October 2002, Vol. 100, No. 8, pp. 3037-3040
BRIEF REPORT
Human leukocyte antigens class II and tumor necrosis factor
genetic polymorphisms are independent predictors of non-Hodgkin
lymphoma outcome
Przemyslaw Juszczynski,
Ewa Kalinka,
Jacques Bienvenu,
Grzegorz Woszczek,
Maciej Borowiec,
Tadeusz Robak,
Marek Kowalski,
Ewa Lech-Maranda,
Lucile Baseggio,
Bertrand Coiffier,
Gilles Salles, and
Krzysztof Warzocha
From the Department of Hematology and Department of
Clinical Immunology, Medical University of Lodz, Poland, and Service
d'Hematologie, Centre Hospitalier Lyon-Sud, and Jeune Equipe
"Pathologie des Cellules Lymphoïdes" Université
Claude Bernard, Lyon, France.
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 TNF376,308,238,163, lymphotoxin alpha (LT )+252, and HLA DRB1 alleles in 204 patients with NHL and 120 controls. TNF308A 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 TNF308A
(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 TNF308A (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.
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