[Effect of gene polymorphism on detoxifying glutathione-S-transferase enzymes on chromosomal stability of squamous epithelial carcinomas in the area of the head-neck].
BACKGROUND
While cigarette smoking and chronic alcohol consumption are the major risk factors for the development of head and neck cancer, it is assumed that genetic factors contribute to risk.


METHODS
We examined genotype frequencies from leukocyte DNA of 269 laryngeal cancer patients, 123 pharyngeal cancer patients and 216 controls. Polymorphisms at different glutathione-S-transferase (GST) gene loci were investigated. Losses of heterozygosity (LOH) at 12 different chromosomal gene loci were determined in 37 of the study patients by comparing blood and tumor cell DNA. The relationship between high risk genotypes and the occurrence of LOH was investigated.


RESULTS
Glutathione-S-transferase high risk genotypes were identified at the first and third genes of the M family (GSTM1, GSTM3) and the first gene of the P family (GSTP1). These high risk genotypes are seen to have a statistically significant influence on the occurrence of LOH in the tumor tissue.


CONCLUSIONS
There is evidence that the polymorphisms studied play a role in the carcinogenic process by influencing the chromosomal fragility which may lead to the inactivation of tumor suppressor genes or the activation of oncogenes.
Matthias
C
C
HNO-Klinik und Poliklinik, Humboldt-Universität, Berlin.
Bockmühl
U
U
Jahnke
V
V
Petersen
I
I
Dietel
M
M
Fryer
A
A
Strange
R C
RC
D000428:Alcohol Drinking / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics*; D002869:Chromosome Aberrations / Q000235:genetics*; D002873:Chromosome Fragility; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D005787:Gene Frequency; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics; D019656:Loss of Heterozygosity; D010039:Otorhinolaryngologic Neoplasms / Q000201:enzymology / Q000235:genetics*; D010610:Pharyngeal Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D005982:Glutathione Transferase
Einfluss von Genpolymorphismen in den entgiftenden Enzymen der Glutathion-S-Transferasen auf die chromosomale Stabilität von Plattenepithelkarzinomen im Kopf-Hals-Bereich.