Polymorphisms of the CYP1A1 and GSTM1 gene involved in oral squamous cell carcinoma in association with a cigarette dose
Introduction
Most environmental procarcinogens require metabolic activation to convert into their respective reactive electrophilic intermediates. Cytochrome P450s (CYP) are the phase I enzymes in the activation pathway. CYP1A1, one of the various forms of CYP, is considered to play an important role in the activation of poly aromatic hydrocarbon compounds (PAH) such as benzo(a)pyrene (BP)[1]. The polymorphic locus at the 264th base downstream from additional polyadenylation signal in the 3′-flanking region of CYP1A1 gene (MspI polymorphism) has been reported to be associated with susceptibility to lung cancer, in particular the histological types of squamous cell carcinoma (SCC) and adenocarcinoma with a low grade differentiation in the Japanese population2, 3. Furthermore, a similar association has been observed in the null genotype of a mu-class isozyme of glutathione S-transferases (GSTM1), which was involved in the detoxification of reactive metabolites of BP[4]. These results suggested that genetically determined variation among individuals in the metabolic activation of such chemical carcinogens makes it possible to explain the individual difference in susceptibility to chemical carcinogenesis.
As the upper aero-digestive tract, the oral cavity has many functions and frequently comes into contact with various chemical compounds. The smoking of tobacco has been commonly regarded as a major risk factor for carcinogenesis of the oral cavity, as has the drinking of alcohol5, 6. However, the pathogenesis of oral cancer, more than 90% of which are SCCs, has not been well understood. In this paper, the genetic polymorphisms of the CYP1A1 and GSTM1 genes among oral SCC patients are considered in order to evaluate the role of the genetic susceptibility in carcinogenesis of the oral cavity.
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Study subjects
The study subjects were 100 Japanese patients (60 males, 40 females; mean age, 59.5 years; range, 43–83 years). They were diagnosed as having oral SCC by the Department of Oral and Maxillofacial Surgery I, Hiroshima University Dental Hospital between 1990 and 1995. The subsites of SCC were the lower gingiva (n=30), the tongue (n=29), the floor of mouth (n=21), the buccal mucosa (n=11) and the upper gingiva (n=9). The control subjects in this study were the patients of the same hospital who were
Distribution of genotypes of CYP1A1 and GSTM1 in patients and controls
The distribution of genotypes of CYP1A1 and GSTM1 among the patients with oral SCC and the controls is shown in Table 1. The presence of the rare homozygote, m2/m2, is observed in 15 patients (15.0%). A comparison with the control group (8.0%) shows that the m2/m2 was significantly more frequent in the patient's group (ORs=3.6, 95% CI:1.4–9.5). The heterozygotic variant, m1/m2, was found in 53 patients (53.0%), thus the m2 allele was observed in a total of 68% of the patients. On the other
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