Annals of Oncology Advance Access originally published online on February 5, 2009
Annals of Oncology 2009 20(6):1094-1099; doi:10.1093/annonc/mdn763
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head and neck cancer |
The regulatory BCL2 promoter polymorphism (–938C>A) is associated with relapse and survival of patients with oropharyngeal squamous cell carcinoma
1 Department of Otorhinolaryngology
2 Institute of Pathology and Neuropathology
3 Department of Radiotherapy
4 Department of Haematology
5 Institute of Pharmacogenetics, University Hospital of Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany
* Correspondence to: Dr H. S. Bachmann, Institute of Pharmacogenetics, University Hospital of Essen, Hufelandstraße 55, D-45147 Essen, Germany. Tel: +49-201-723-3459; Fax: +49-201-723-5968; E-mail: hagen.bachmann{at}uk-essen.de
Background: Expression of the antiapoptotic and antiproliferative protein B-cell lymphoma 2 (Bcl-2) has been repeatedly shown to be associated with better locoregional control and patients’ survival in oropharyngeal squamous cell carcinoma (OSCC). A regulatory (–938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generates significantly different BCL2 promoter activities and has been associated with outcome in different malignancies. The aim of the present study was to analyze the possible influence of the (–938C>A) SNP on survival of patients suffering from OSCC.
Materials and methods: One hundred and thirty-three patients with primary OSCC were retrospectively investigated. Bcl-2 expression of tumor cells was demonstrated by means of immunohistochemistry. Both the Bcl-2 expression and the (–938C>A) genotypes were correlated with the patients’ survival.
Results: The (–938C>A) SNP was significantly related to Bcl-2 expression (P = 0.008). Kaplan–Meier curves revealed a significant association of the –938 SNP with relapse-free (P = 0.0283) and overall survival (P = 0.0247). Multiple Cox regression identified the BCL2 (–938CC) genotype as an independent prognostic factor for relapse [hazard ratio (HR) 1.898, P = 0.021] as well as for death in OSCC patients (HR 1.897, P = 0.013).
Conclusions: The (–938C>A) SNP represents a potential novel prognostic marker in patients with OSCC that could help to identify a group of patients at high risk for relapse and death.
Key words: BCL2 gene, oropharynx, polymorphism, survival, squamous cell carcinoma
Member of the West-German Cancer Center Essen (WTZE). Received for publication September 10, 2008. Revision received November 24, 2008. Accepted for publication November 25, 2008.