TNF Polymorphisms Independently Predict Outcome in Patients with B-Cell Non-Hodgkin’s Lymphoma

NF Osman; TL Holyoake; A Zeineldin; Amal A Elkordy; IG McQuaker

International Journal of Cancer Management

The Official Journal of Cancer Research Center (CRC), Shahid Beheshti University of Medical Sciences

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TNF Polymorphisms Independently Predict Outcome in Patients with B-Cell Non-Hodgkin’s Lymphoma

Author(s):

NF Osman¹,

TL Holyoake¹,

A Zeineldin²,

Amal A Elkordy ^3,*,

IG McQuaker¹

1Section of Experimental Haematology and Department of Clinical and Laboratory Haematology, Royal Infirmary, Glasgow, United Kingdom

2Menoufia University Hospitals, Shebin El-kom, Egypt

3Department of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, United Kingdom

International Journal of Cancer Management:Vol. 2, issue 1; e80500

Published online:Mar 30, 2009

Article type:Research Article

Received:Mar 30, 2009

Accepted:Mar 30, 2009

How to Cite:NF OsmanTL HolyoakeA ZeineldinAmal A Elkordy IG McQuakerTNF Polymorphisms Independently Predict Outcome in Patients with B-Cell Non-Hodgkin’s Lymphoma.Int J Cancer Manag.2(1):e80500.

Abstract

Objectives: Tumour Necrosis Factor α (TNFα) and Lymphotoxin α (LTα) have been implicated in the pathogenesis of lymphoproliferative disorders. Patients with B-cell non-Hodgkin’s lymphoma (NHL) often have high serum levels of TNF which may be associated with a poor outcome. TNFα and LTα polymorphisms are known to influence expression of these cytokines and may explain the variable response to therapy.

Patients and Methods: In patients with NHL, serum levels of TNFα and LTα were measured. DNA was typed using allele specific PCR and restriction fragment length polymorphism for the –308 TNFα and +252 LTα polymorphisms and comparison was made with clinical outcome.

Results: The presence of high producing alleles was significantly associated with high serum levels of TNFα and LTα. The presence of 2 or more high producing alleles was significantly associated with more advanced disease at presentation (stage III and IV), p=0.024, a higher International Prognostic Index (IPI) score, p=0.038, failure to achieve a complete remission (CR) after 1st line therapy (88% vs 33%, p=0.01) and shorter progression free survival (PFS) (median 24 months compared with 78 months, p=0.001). Multivariate analysis confirmed that TNF highrisk haplotype (HRH) was an independent prognostic factor for PFS.

Conclusions: These results demonstrate that TNF polymorphisms are independent prognostic factors in NHL. Further study is required to further define the importance of TNF polymorphisms within different lymphoma subtypes and with different therapeutic approaches.

Keywords

B-cell Non-Hodgkin’s lymphoma

survival

TNF polymorphisms

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