Elsevier

Oral Oncology

Volume 36, Issue 3, May 2000, Pages 267-271
Oral Oncology

Genetically high susceptibility to oral squamous cell carcinoma in terms of combined genotyping of CYP1A1 and GSTM1 genes

https://doi.org/10.1016/S1368-8375(99)00090-1Get rights and content

Abstract

An association of oral squamous cell carcinoma (SCC) susceptibility with an MspI restriction site polymorphism of the CYP1A1 gene and GSTM1 polymorphism were reported in our previous study (Sato M, Sato T, Izumo T, Amagasa T. Genetic polymorphism of drug-metabolizing enzymes and susceptiblility to oral cancer. Carcinogenesis 1999;20:1927–31). We report here that genetic risk for oral SCC was associated with another isoleucine–valine (Ile–Val) polymorphism, which resulted in an Ile–Val amino acid replacement in the heme-binding region of CYP1A1, and combined genotyping of CYP1A1 and GSTM1 genes in relation to the cumulative cigarette-smoking dose. The genetic polymorphisms of CYP1A1 and GSTM1 genes in oral cancer susceptibility were assessed by examining polymorphic prevalences in 142 oral SCC patients and 142 healthy controls who were individually matched to the patients with respect to sex and age (±1 year). Individuals with a combined genotype of Val/Val and GSTM1(−) were at an increased risk for oral SCC compared with other combined genotypes, in particular, at a low dose level of cigarette smoking.

Introduction

Most chemical carcinogens require metabolic activation by Phase I enzymes cytochrome P-450s, and detoxification by conjugation via the various Phase II enzymes (epoxide hydrolase, glutathione S-transferase, N-acetyltransferase and sulfotransferase, etc.) [2]. Thus, the coordinated expression and regulation of Phase I and II drug-metabolizing enzymes and their metabolic balance may be an important host factor to determine whether exposure to carcinogens results in cancer or not [3], [4], [5]. We have previously shown that individuals at genetically high risk of oral squamous cell carcinoma (SCC) could be screened in relation to the MspI polymorphism in the 3′ flanking region of the CYP1A1 gene and the GSTM1 polymorphism and cigarette-smoking dose [1]. Recently, another polymorphism of CYP1A1 gene, the isoleucine–valine (Ile–Val) polymorphism, has been associated with an increased risk for tobacco-related diseases such as lung and oral cancers [6], [7], [8], [9], [10]. In this study, we identified individuals with genetically high risk of oral SCC in terms of combined Ile–Val genotyping of CYP1A1 and GSTM1 genes in relation to cigarette-smoking dose in a Japanese population.

Section snippets

Study subjects

All of the 142 oral SCC patients were histopathologically diagnosed in the Saitama Cancer Center Hospital (78 males, 64 females). Patients consenting to participate in our study were interviewed at the time of their first admission using a standardized questionnaire concerning their cigarette- and alcohol-consumption history. We also collected DNA samples from 142 consenting healthy controls who were individually matched to the patients with respect to sex and age (±1 year), who were randomly

Results

The distribution of genotypes of CYP1A1 and GSTM1 among oral SCC patients and healthy controls is shown in Table 1. A predominant homogygote (Ile/Ile), the heterozygote (Ile/Val), a rare homozygote (Val/Val) were found, respectively, in 90 (63.4%), 46 (32.4%) and 6 (4.2%) individuals among the healthy controls. This result gave a good fit to the Hardy–Weinberg equilibrium with a gene frequency of 0.796 for Ile/Ile and 0.204 for Val/Val. On the other hand, type Ile/Ile, Ile/Val, Val/Val were

Discussion

A difference in susceptibility to smoking-related cancers such as lung, head and neck cancers in terms of germ-line polymorphisms of the CYP1A1 and GSTM1 genes, taking into account the consumed amount of cigarettes, has already been reported [6], [7], [8], [9], [10], [13], [14], [15]. In this study, we investigated whether an association of oral SCC with Ile–Val polymorphism of CYP1A1 and GSTM1 polymorphism in relation to the cigarette-smoking dose existed in a Japanese population.

The Val/Val

Acknowledgments

We thank Dr. K. Kawajiri, Department of Biochemistry, Saitama Cancer Center Research Institute, for his technical advice, Dr. S. Okabe, Department of Oral Surgery, Saitama Cancer Center Hospital for collecting blood samples from patients, and Dr. K. Kino, Maxillofacial Surgery, Graduate School, Tokyo Medical and Dental University for his statistical advice.

References (18)

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