氯乙烯工人P53腫瘤蛋白研究

氯乙烯是已知的肝毒性致癌物 質，會導致肝臟血管肉瘤和肝細胞 癌。過去的文獻報告指出，氯乙烯暴 露相關之肝臟血管肉瘤病例，出現p53 基因之突變，且此種突變專一性高。此特性讓我們可以利用血清中的anti-p53 抗體與p53 蛋白來作為研究氯乙烯相關之致癌性研究之替代對象。本研究探討氯乙烯工人體內p53 基因突變，與基因多型性CYP2E1 ， ALDH ，EH ，和GSTs 。以及生活習慣 如年紀，抽煙，飲酒及體內微量維生 素間的關係。共計有213 位氯乙烯工 人被納入分析，根據過去累積暴露氯 乙烯劑量分成高，低暴露組。利用問 卷訪視獲得其飲酒及吸煙習慣，工作 史及個人病史。氯乙烯工人的p53 基 因突變是以ELISA 的方式偵測，基因 多型性CYP2E1 ，ALDH ，EH ，和GSTs 是以聚合脢鎖鍊反應(PCR)來測定，微 量維生素則是以高效能液相色層層析儀(HPLC)來偵測。結果顯示p53 突變蛋白或抗體陽性率為13.6%。P53 抗原陽性在 ALDH2 基因型有40.9%的人為wild type ，而p53 抗原陰性這組有59.2%的 人為wild type ，利用邏輯式回歸分析 控制生活習慣，基因型及微量維生素 後可看到在基因型ALDH2 和P53 抗原 陽性有顯著相關(p<0.05)。而P53突變蛋白或抗體陽性這組我們可以看 到微量維生素維生素A 在兩組有顯著 的差異(chi-square, p=0.05)。利用邏輯 式回歸分析控制生活習慣，基因型及 微量維生素後可看到在微量維生素維 生素A 和P53 抗原及抗體陽性有顯著 相關(p<0.05)。Vinyl chloride workers are known to be at risk for the development of angio-sarcoma and hepato-cellular carcinoma of the liver. In a study of p53 gene mutations in the tumors of vinyl chloride exposed workers, 2 of 4 cases (50%) of angio-sarcoma of the liver examined contained the specific vinyl chloride induced p53 tumor suppressor gene mutation. Because of the specificity of the mutation, p53 antigen and anti-p53 antibodies can be used as surrogate for p53 mutation. This study was designed to investigate whether the metabolic genotypes, lifestyle and micronutrients affect VCM-induced p53 mutation. Two hundred and thirteen male VCM-workers were classified into high and low exposed groups. Questionnaires were administered to obtain detailed histories of cigarette smoking, alcohol consumption, occupations, and medications. The mutant p53 protein and anti-p53 antibodies were detected by enzyme-linked immunosorbent assays. CYP2E1, ALDH2, EH and GSTs genotypes were identified using the polymerase chain reaction (PCR). Micronutrients were quantified by high-performance- liquid-chromatography (HPLC). The results showed that 29 of 213 vinyl chloride workers(13.6%) had mutant p53 antigen or antibodies. 40.9% of p53 antigen positive workers had ALDH wild type compared to 59.2% of p53 antigen negative. In logistic regression analysis after adjusted the lifestyle, genotypes and micronutrients, we can find that genotype ALDH2 had significant correlation with p53 antigen (p