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題名 | 鼻咽癌多重危險因子之世代追蹤研究=A Cohort Study on Multiple Risk Factors of Nasopharyngeal Carcinoma |
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作者 | 林宇旋; 陳建仁; Lin, Yu-hsuan; Chen, Chien-jen; |
期刊 | 中華公共衛生雜誌 |
出版日期 | 19971200 |
卷期 | 16:6 1997.12[民86.12] |
頁次 | 頁466-477 |
分類號 | 416.879 |
語文 | chi |
關鍵詞 | 鼻咽癌; 世代追蹤研究; 危險因子; Nasopharyngeal carcinoma; Cohort study; Risk factors; |
中文摘要 | 氯乙烯是一種具有肝毒性的致癌物,可以引起肝功能異常、肝纖維化、肝硬化及 肝血管肉瘤。 氯乙烯可經由細胞色素 P45O 2El(CYP2El) 酵素的活化而形成中間代謝物 -chloro- ethylene oxide 及 chloroacetaldehyde, 造成細胞的損傷或進一步由麩胺基硫 轉移�t (GSTs) 代謝排出體外。 本研究收集 251 名聚氯乙烯員工來採討上述代謝酵素的多 形性是否會影響氯乙烯暴露所造成的肝功能異常。氯乙烯的暴露分組是根據員工的工作項目 及空氣中的氯乙烯濃度 (TWA 大於及小於 l ppm) 分成高、低兩組。肝功能是以天門冬酸轉 胺基�t (AST) 及氨基丙酸轉胺基�t (ALT) 的活性來作指標。 GST T1、 GST Ml 和 CYP2El 基因的多形性是利用聚合�t鏈鎖反應 (Polymerase chain reaction,PCR) 及限制片段長度 多形性分析 (restriction fragment) length polymorphim, RFLP) 之方法分析。另外收集 個人基本資料、工作史、吸菸及喝酒的習慣與身體質量指數等。此外,B 型肝炎病毒表面抗 原與 C 型肝炎病毒抗體也加以分析。 若以氯乙烯暴露分組作分層分析,發現在低氯乙烯暴 露時, GST T1 非無效基因型較容易有 Alt 指標異常 (OR=3.8, 95% CI=1.2-14.5, p<0.05),CYP2El 基因型與 ALT 指標異常無明顯相關; 但在高氯乙烯暴露時,GST Tl 非無 效基因型之危險性反而較不明顯 (OR=O.9, 95% CI= 0.2-3.8, p>O.1), CYP2El c2c2 基因 型則與 ALT 指標異常有 (OR=4.8, 95% CI=0.6-34.8, P= 0.08)。納入 GST Tl、CYP2El 基 因型與氯乙烯暴寒交互作用項之多變項對數迴歸分析也有類似的結果發現。因此 GST T1 與 CYP2El 酵素在氯乙烯代謝解毒的途徑上可能扮演重要的角色, 並且在不同濃度的氯乙烯暴 露時,對肝功能異常可能有不同的效應。 |
英文摘要 | Vinyl chloride monomer (VCM) is hepatotoxic as well as carcinogenic in humans. There are reports that exposure to VCM seems to induce abnormal liver function, liver fibrosis, cirrhosis, and angiosarcoma of the liver. In vive, VCM is metabolized by cytochrome P450 2E 1 (CYP2El) to form chloroethylene oxide (CEO) and chloroactetaldehyde (CAA), both electrophilic metabolites, which may either cause cell damage or are further metabolized and detoxified by glutathione S-transferases(GSTs). This study investigated whether or not the genotypes, CYP2E1, glutathione Stransferase θ (GST T1) and M (GST Mi), cor- related the abnormal liver function in vinyl chloride exposed workers. We enrolled 251 workers from 5 polyvinyl chloride plants for this study. The workers who were exposed to VCM were classified into two, high and low exposure groups and the degree of exposure was determined based on their job titles and airborne VCM concentration. The enzyme activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were used as the parameters of liver function. The genotypes, CYP2E1,GST T1 and GST M1, were determined by performing PCR and RFLP on peripheral white blood cell DNA. Other potential risk factors were also ascertained and the confounding effect was adjusted accordingly. Stratified analyses were used to explore the correlation between the alteration of liver function and the genotypes, CYP2E1, GST T1 and GST M1, among the workers exposed to different levels of VCM. The results obtained showed:(l)at low VCM exposure, the odds ratio (OR) of GST T1 non-null genotype on abnormal ALT was 3.8 (95% CI = 1.2-14.5) but the CYP2E1 gen- otype was not associated with abnormal ALT; (2)at high VCM exposure, on the other hand, a c2c2 CYP2E1 genotype was associated with increased OR on abnormal ALT (OR=4.8, 95% CI = 0.6-34.8) but the GST T1 non-null genotype was not associated with abnormal ALT (OR = 0.9, 95% CI = 0.2-3.8); and (3)multipie logistic regression also showed strong interactions of the VCM exposure to CYP2E1 as well as to the GST T1 genotype. Thus, These observations suggest that the two genotypes, CYP2E1 and GST T1, may play important roles in the biotransformation of VCM, whose effeet leads to liver damage. |
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