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Microsatellite GTn‐repeat polymorphism in the promoter of heme oxygenase‐1 gene is an independent predictor of tumor recurrence in male oral squamous cell carcinoma patients
Author(s) -
Vashist Y. K.,
Blessmann M.,
Trump F.,
Kalinin V.,
Kutup A.,
Schneider C.,
Gawad K.,
Kaifi J. T.,
Schmelzle R.,
Izbicki J. R.,
Yekebas E. F.
Publication year - 2008
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.2008.00639.x
Subject(s) - genotype , allele , heme oxygenase , medicine , biology , gastroenterology , promoter , oncology , gene , cancer research , genetics , heme , gene expression , biochemistry , enzyme
Background: Transcriptional activity of the heme oxygenase‐1 gene (HMOX‐1) is modulated by a GTn‐repeat promoter polymorphism. The long GTn‐repeat allele has been previously reported to be associated with increased risk of oral squamous cell carcinoma (OSCC) in male areca chewer and short GTn‐repeat allele has been proposed to have protective properties in OSCC patients. The aim of the present study was to correlate the GTn‐repeat genotypes with clinicopathological characteristics along with clinical outcome of non‐areca chewer OSCC patients. Methods: DNA of 99 patients that underwent complete surgical resection of OSCC was analyzed for GTn‐repeat polymorphism in the HMOX‐1 promoter by polymerase chain reaction, capillary electrophoresis and DNA sequencing. Results: Seven SS (7.1%), 51 SL (51.5%) and 41 LL (41.4%) genotypes were found. In a total of 14 (14.1%) patients, tumor recurrence (TR) was observed. There was no TR in the SS allele carriers. In SL carriers three and in LL 11 TR occurred ( P = 0.009, chi‐squared test). Mean relapse‐free survival was 109.2 months in SL allele carriers compared with 72.3 months in LL allele carriers ( P = 0.01, log‐rank test). Multivariate Cox regression modeling identified GTn‐repeat genotype as an independent prognostic factor ( P = 0.03; relative risk (RR) 4.1; 95% CI 1.1–14.6). Conclusion: Presence of S allele was associated with a lower TR rate and better relapse‐free survival in OSCC patients. HMOX‐1 promoter polymorphism might be considered as a potential prognostic marker in OSCC patients.