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Risk of chemotherapy-induced pulmonary fibrosis is associated with polymorphic tumour necrosis factor-a2 gene

¹ Postgraduate School of Molecular Medicine, Medical University, Warsaw and Dept of Tumour Pathology Institute of Oncology, Cracow, Poland. ² Transplantation Immunology Unit, Hospital Cantonal, Geneva, Switzerland. ³ Radiotherapy centre, Katowice, Poland. ⁴ Dept of Pathology, University of Geneva, Geneva, Switzerland

CORRESPONDENCE: P.F. Piguet, Dept of Pathology, 1 rue M. Servet, CMU, 1211, Geneva, Switzerland. Fax: 41 227025746. E-mail: pierre.piguet@medecine.unige.ch

Keywords: bleomycin, Hodgkin's lymphoma, human leukocyte antigen-DR, pulmonary fibrosis, tumour necrosis factor

Received: April 20, 2001
Accepted October 17, 2001

This work was supported in part by grants no. 31-56839.99, 31-57557.99, 32-52061.97 from the Swiss National Science Foundation. J. Libura is supported by the Marek-Rutkowski Foundation.

In some patients, chemotherapy (CHT) of cancer can result in pulmonary inflammation and fibrosis, eventually leading to respiratory insufficiency.

As animal studies have underlined the importance of major histocompatibility complex (MHC) genes in the susceptibility to bleomycin (BLM)-induced pulmonary fibrosis, the authors typed human leukocyte antigen-DR (HLA-DR) and tumor necrosis factor (TNF) genes in patients treated for Hodgkin's disease by a therapy including bleomycin.

Patients were divided into pulmonary responders (PR) (n=21) or nonresponders (PNR) (n=20) on the basis of pulmonary alterations detected on chest radiography and the cumulated amount of BLM injected. The incidence of TNFa2, a microsatellite allele in the promoter region of the TNFB gene reported to be associated with increased TNF- production, was significantly higher in PR than PNR (65% versus 19%). HLA-DRB1*15 showed a weak but nonsignificant association with the PR phenotype (50% versus 14%), as well as HLA-DRB1*03 (30% versus 19%) and TNFA-308*2 (30% versus 14 %). TNFa2 and DR15 were independent risk factors and the occurrence of either genetic marker was 85% versus 29% in the PR and PNR groups respectively.

Thus, the polymorphic TNFa2 microsatellite is associated with a risk of chemotherapy-induced pulmonary fibrosis.

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