Haeme oxygenase-1 promoter polymorphism is an independent prognostic marker of gastrointestinal stromal tumour.
OBJECTIVE
Gastrointestinal stromal tumours (GISTs) display genetic alterations on chromosome 22. GTn repeat (GTn) length polymorphism in the promoter of haeme oxygenase-1 gene (HMOX-1) is located on chromosome 22 and associated with malignant growth. The aim was to investigate the role of HMOX-1 promoter polymorphism in GIST patients.


RESULTS
Tumour and corresponding healthy tissue DNA of 44 patients who underwent surgical resection of GIST were analysed by polymerase chain reaction, capillary electrophoresis and DNA sequencing. GTn polymorphism was classified into short (S) and long (L) allele. There was no difference detected in GTn genotype between tumour and healthy tissue DNA. Short GTn allele (SGTn) was significantly associated with metastatic disease, higher tumour recurrence rates and high risk GIST (consensus criteria 2001). Furthermore, SGTn allele carriers had significantly shorter disease-free and overall survival (log rank test, P < 0.0001). On multivariate Cox regression analysis, GTn polymorphism was identified as an independent prognostic factor for survival (P = 0.001).


CONCLUSIONS
HMOX-1 promoter GTn polymorphism is a potential prognostic marker and may help to allocate patients to different risk groups, customized therapy and follow-up. Haeme oxygenase-1 could represent an important candidate gene in the pathogenesis and growth of GIST.
Vashist
Yogesh K
YK
Department of General, Visceral and Thoracic Surgery, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. vashist@uke.uni-hamburg.de
Uzunoglu
Guentac
G
Cataldegirmen
Guelle
G
Kalinin
Viacheslar
V
Schurr
Paulus
P
Koenig
Alexandra M
AM
Thieltges
Sabrina
S
Zehler
Oliver
O
Schneider
Claus
C
Izbicki
Jacob R
JR
Yekebas
Emre F
EF
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*
D014408:Biomarkers, Tumor; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1