Glutathione S-Transferase and N-Acetyltransferase Genotypes and Asbestos-Associated Pulmonary Disorders

作者：Ari Hirvonen, T. S. Sirkku, Kaija Linnainmaa, Kari Tapio Koskinen, Kirsti Husgafvel‐Pursiainen, Karin V. Mattson, Harri Vainio · 发表于：JNCI Journal of the National Cancer Institute · 年份：1996 · DOI：10.1093/jnci/88.24.1853 · 被引用次数：143 · 研究领域：Glutathione Transferases and Polymorphisms、Carcinogens and Genotoxicity Assessment、Occupational and environmental lung diseases

BACKGROUND: Humans vary in their ability to metabolize endogenous and exogenous compounds. Glutathione S-transferases (GSTs) and N-acetyltransferases (NATs) are enzymes involved in the detoxification of hazardous agents. The GSTM1 and GSTT1 genes exhibit null (i.e., deletion) polymorphisms; in specific individuals, homozygous deletion (i.e., both copies lost) of these genes can be detected. Polymorphism of the NAT2 gene results in slow and fast acetylators of potentially toxic substances. The GSTM1-null and the NAT2 slow-acetylator genotypes have been associated with increased risks for the development of environmentally induced cancers. PURPOSE: We assessed whether homozygous GSTM1-null or GSTT1-null genotypes or the NAT2 slow-acetylator genotype were associated with increased risks for the development of malignant and nonmalignant asbestos-related pulmonary disorders in a cohort of Finnish construction workers. METHODS: The study population consisted of 145 asbestos insulators who were classified as having been exposed to high levels of asbestos; 69 of these individuals had no pulmonary disorders (control subjects), and 76 had either malignant mesothelioma (n = 24) or nonmalignant pulmonary disorders, such as asbestosis and/or pleural plaques (n = 52). Lymphocyte DNA and the polymerase chain reaction were used to determine the GSTM1, GSTT1, and NAT2 genotypes of the study subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) estimating the relative risks of disease...