| Summary: | 碩士 === 國立臺灣大學 === 流行病學研究所 === 87 === The specific aim of this study is to elucidate the association between arsenic methylation capability and genotypes of glutathione S-transferases (GST M1, T1 and P1), and the associations with arsenic-induced skin cancer for genotypes of GST''s and p53, arsenic methylation capability and cumulative arsenic exposure. A total of 1081 residents aged 30 years or older were recruited between September 1988 and June 1989 from three arseniasis-hyperendemic villages in southwestern Taiwan. There were 37 cases and 120 controls included in this nested case-control study. Biological specimens were collected through annual health examinations. Arsenic levels in urine were speciated by high performance liquid chromatography and quantified by hydride generator combined with atomic absorption spectrometry. DNA extracted from peripheral lymphocytes was analyzed to determine genotype of GST M1, T1 and P1 and p53 by polymerase chain reaction with/without restriction fragment length polymorphism method.
The results showed that the primary arsenic methylation index increased with total urinary arsenic and age. Subjects with null genotypes of GST M1 or T1 or a mutant allele of P1 had a higher primary arsenic methylation index than those with non-null genotypes of GST M1 and T1 and wild type of GST P1. There was a reverse interactive effect on primary arsenic methylation index between GST genetic polymorphisms and age. Secondary arsenic methylation index was found to decrease with age and increase with total urinary arsenic. Subjects with null genotypes of GST M1 or T1 or a mutant allele of P1 had a lower secondary arsenic methylation index than those with non-null genotypes of GST M1 and T1 and wild type of GST P1. There was a positive interactive effect on secondary arsenic methylation index between GST genetic polymorphisms and age.
Subjects having a null or mutant type of GST had an increased risk of arsenic-induced skin cancer showing an odds ratio of 6.1 (95﹪confidence interval, 1.4-26.8). The higher the cumulative exposure to inorganic arsenic through drinking well water, the higher the risk of developing skin cancer. The poorer the arsenic methylation capability, the higher the risk of arsenic-induced skin cancer. Subjects who had any null or mutant genotypes of GST M1, T1 and P1, poor arsenic methylation capability and high exposure to arsenic had a much increased risk of skin cancer than those who with non-null and wild genotypes of GST M1, T1 and P1, good arsenic methylation capability and low exposure to arsenic ( odds ratio=9.1, p value=0.02 ). No association between p53 genetic polymorphism and arsenic-induced skin cancer was found.
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