RESUMO
BACKGROUND: Glutathione S-Transferase mu (GSTM) is a phase II detoxification enzyme, which rapidly detoxifies carcinogens found in tobacco smoke. The prevalence of this polymorphism is about 50% in the caucasian population. The lack of GSTM1 has been linked with an increased susceptibility of smoking related cancers. A homozygote deletion of the GSTM-gene results in a missing gene product. The objective of this study was to investigate the frequency of the GSTM1 null genotype in squamous cell carcinoma of head and neck, especially the larynx and hypopharynx and to analyse the occurrence with respect to certain anatomical sites of cancer. MATERIAL AND METHODS: The GSTM1 genotypes of 83 patients with head and neck cancers and 60 healthy controls were determined by polymerase chain reaction (PCR) using blood leukocyte DNA. The presence or absence of the PCR-product after electrophoretic separation in an 2.0% agarose gel revealed the positive or negative genotype. RESULTS: The absence of the GSTM1 gene (null genotype) was found in 64% of all head and neck cancer patients and in 48% of the healthy controls (p < 0.05). Separating for cancer site, the null genotype was found in 44% of patients with hypopharyngeal cancer and in 78% of patients with laryngeal cancer (p < 0.05). The protein concentration of GSTM-enzyme correlated with the genotype. CONCLUSIONS: The results suggest that GSTM1 deficiency predisposes to head and neck cancer, especially to cancer of the larynx, which is particularly exposed to tobacco smoke carcinogens.
Assuntos
Carcinoma de Células Escamosas/genética , Glutationa Transferase/genética , Neoplasias de Cabeça e Pescoço/genética , Adulto , Idoso , Sequência de Bases , Distribuição de Qui-Quadrado , DNA/genética , Primers do DNA , Feminino , Deleção de Genes , Predisposição Genética para Doença , Genótipo , Homozigoto , Humanos , Neoplasias Hipofaríngeas/genética , Neoplasias Laríngeas/genética , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Neoplasias Bucais/genética , Neoplasias Orofaríngeas/genética , Polimorfismo Genético , Fumar/efeitos adversosRESUMO
The centromeric heterochromatin of all human chromosomes is composed of tandemly repeated alpha satellite DNA. Here we describe another alphoid subfamily that maps to human chromosome 22 as determined by FISH. The alphoid sequences were isolated from three YAC-clones carrying DNA from the pericentromeric region of the short arm of human chromosome 22 and limited amounts of alphoid DNA. This property enabled us to map the members of the subfamily to the border of the centromeric region and the short arm of the chromosome. The new alphoid subfamily may contribute to the closure of the gap remaining between the centromeric and short-arm maps of human chromosome 22.
