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.
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).


CONCLUSIONS
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.
Vashist
Y K
YK
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. vashist@uke.uni-hamburg.de
Blessmann
M
M
Trump
F
F
Kalinin
V
V
Kutup
A
A
Schneider
C
C
Gawad
K
K
Kaifi
J T
JT
Schmelzle
R
R
Izbicki
J R
JR
Yekebas
E F
EF
D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000556:secondary / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D005838:Genotype; D006147:Guanine; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000601:surgery; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012189:Retrospective Studies; D012737:Sex Factors; D013941:Thymine
D006147:Guanine; D051547:Heme Oxygenase-1; D013941:Thymine