Haeme oxygenase-1 promoter polymorphism is an independent prognostic marker of gastrointestinal stromal tumour
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Haeme oxygenase-1 promoter polymorphism is an independent prognostic marker of gastrointestinal stromal tumour. / Vashist, Yogesh K; Uzunoglu, Guentac; Cataldegirmen, Guelle; Kalinin, Viacheslar; Schurr, Paulus; Koenig, Alexandra M; Thieltges, Sabrina; Zehler, Oliver; Schneider, Claus; Izbicki, Jacob R; Yekebas, Emre F.
in: HISTOPATHOLOGY, Jahrgang 54, Nr. 3, 02.2009, S. 303-8.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Haeme oxygenase-1 promoter polymorphism is an independent prognostic marker of gastrointestinal stromal tumour
AU - Vashist, Yogesh K
AU - Uzunoglu, Guentac
AU - Cataldegirmen, Guelle
AU - Kalinin, Viacheslar
AU - Schurr, Paulus
AU - Koenig, Alexandra M
AU - Thieltges, Sabrina
AU - Zehler, Oliver
AU - Schneider, Claus
AU - Izbicki, Jacob R
AU - Yekebas, Emre F
PY - 2009/2
Y1 - 2009/2
N2 - AIMS: 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.METHODS AND 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.
AB - AIMS: 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.METHODS AND 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.
KW - Biomarkers, Tumor
KW - Female
KW - Gastrointestinal Stromal Tumors
KW - Heme Oxygenase-1
KW - Humans
KW - Male
KW - Middle Aged
KW - Polymorphism, Genetic
KW - Promoter Regions, Genetic
U2 - 10.1111/j.1365-2559.2009.03221.x
DO - 10.1111/j.1365-2559.2009.03221.x
M3 - SCORING: Journal article
C2 - 19236506
VL - 54
SP - 303
EP - 308
JO - HISTOPATHOLOGY
JF - HISTOPATHOLOGY
SN - 0309-0167
IS - 3
ER -