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研究生:黃莉萍
研究生(外文):Li-Ping Huang
論文名稱:男性氯乙烯單體暴露、代謝基因多型性及其配偶懷孕所需時間
論文名稱(外文):Male Vinyl Chloride Monomer Exposure, Metabolic Gene Polymorphism and Time to Pregnancy Study
指導教授:張蓓貞張蓓貞引用關係陳保中陳保中引用關係
指導教授(外文):Pei-Jen ChangPau-Chung Chen
學位類別:碩士
校院名稱:國立台北護理學院
系所名稱:護理研究所
學門:醫藥衛生學門
學類:護理學類
論文出版年:2003
畢業學年度:91
語文別:中文
中文關鍵詞:氯乙烯單體聚氯乙烯代謝基因多型性受孕所需時間受孕能力
外文關鍵詞:vinyl chloride monomer(VCM)polyvinyl chloride (PVC)time to pregnancygenetic polymorphismsfecundibility
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塑膠工業是台灣極重要的產業之一,而氯乙烯單體(VCM)則是塑膠工業中很重要的原料物,國際癌症研究機構將氯乙烯定為第一類致癌物,且許多研究均顯示氯乙烯單體是一種具有肝毒性的致癌物質會導致癌症及其他肝臟疾病,雖然國內氯乙烯聚合工人世代曾發表過肝功能異常、肝硬化或肝癌、及基因傷害相關的論文,但並不曾探討氯乙烯單體對生殖系統及下一代的影響,因此值得進一步探討男性氯乙烯聚合工人世代的生育能力。
本研究分為受孕所需時間及代謝基因多形性的修飾作用兩部份,以回溯性世代研究法,選擇國內三家聚氯乙烯工廠男性員工,已婚有配偶且小孩年齡≦14歲,進行男性氯乙烯工人配偶的問卷訪視,以收集詳細懷孕史及其他潛在干擾因子,並測量其配偶受孕所需時間(TTP),同時也將收集男性工人之血液檢體,以分析其基因多型性,以探討氯乙烯單體暴露與基因多型性對配偶受孕所需時間之影響。
本研究樣本共217個孕次,分高、低、無暴露組各有28、151、38個有效孕次,在控制教育程度、抽煙、受孕年齡、輪班、生活習慣及孕次等潛在干擾因子後,發現低暴露組之調整受孕比0.87(95 % CI=0.58-1.32),高暴露組之調整受孕比0.60(95 % CI=0.34-1.05),隨著聚氯乙烯工人暴露濃度愈高,其配偶生育能力有下降現象。
在代謝基因多型性方面,選擇與氯乙烯最相關的易感性指標CYP2E1、ALDH2及GSTT1為主要的指標,有抽血資料共106個孕次納入分析。由本研究可看出若基因型為CYP2E1 c1c2型在高暴露濃度(>5 ppm)時,其受孕所需時間≧7個月所佔的比例最高(37.5﹪),而ALDH2 1-1型在低暴露濃度(≦5 ppm)時,其受孕所需時間≧7個月所佔的比例最高(21.1﹪)。
本研究結果指出男性氯乙烯聚合工人暴露於氯乙烯單體,隨著暴露濃度愈高,對其配偶的生育力影響愈大;另外男性氯乙烯工人其代謝基因多形性,對氯乙烯暴露與配偶的生育力未具有修飾作用(modification effect)。
Vinyl chloride polymorization is one of major industries in Taiwan and vinyl chloride monomer (VCM) an important material for plastic industry. VCM has been classified by the International Agency for Rearch on Cancer as a group one carcinogen. Although there were several published works on abnormal liver functions, liver cirrhosis or cancer, and genetic damages of the Taiwan polyvinyl chloride (PVC) cohort, the potential effect of VCM exposure on reproduction has not yet been studied. Now it is a chance to investigate the effect of male VCM exposure on fecundability measured by time to pregnancy, and to explore metabolic gene polymorphism modification effect on its relationship. A retrospective time to pregnancy study was conducted among the wives of male workers in three PVC factories in Taiwan, who have children with the age less than 14 years. The detailed pregnancy history including TTP for each conception and potential confounders was collected by face-to-face interview, and collected male worker''s blood data to analysised gene polymorphism.
This study population consisted of 217 pregnancies. The latter will be grouped into pregnancies to non-exposure , low-exposure (<5 ppm), and high-exposure (>5ppm). Compared with the non-exposure group (N=38), fecundability in the low exposure group (N=151) (FDR=0.87, 95 % CI=0.58-1.32) but that in high exposure group (N=28) decreased (FDR=0.60, 95% CI=0.34-1.05) after controlling education, smoking, age of conceived, and other potential confounders.
To explore the modification effect of genetic polymorphisms, we used metabolic gene GSTT1, CYP2E1 and ALDH2. The result showed 37.5% of time to pregnancies were ≧7 months in high exposure CYP2E1 c1c2 and showed 21.1% of time to pregnancies were ≧7 months in low exposure ALDH2 1-1.
In conclusion, there were some evidence of VCM exposure on male fecundability although no statistical significance. However, no modification effect of
第壹章、緒論
第一節、前言………………………………………..………….…1
第二節、研究目的…………………………………..………….…2
第三節、研究假設… ……………………………..……….……2
第貳章、文獻查證
第一節、氯乙烯單體的暴露與代謝途徑之研究………….………4
第二節、氯乙烯與相關癌症之研究……………………….………7
第三節、氯乙烯與基因毒性之研究………………..…….………8
第四節、代謝基因多型性……………………………….……….10
第五節、氯乙烯單體對生殖能力之影響…….………………….10
第六節、受孕能力測量工具……………………………………..14
第參章、材料與方法
第一節、研究設計…………………………………………….…16
第二節、研究對象…………………………………………………………….17
第三節、生物標記…………………………………………….…19
第四節、問卷測量…………………………………………………………….19
第五節、暴露分層…………………………………………………………….21
第六節、統計分析……………………………………….…25
第肆章、研究結果
第一節、研究對象的基本資料……………………….……27
第二節、研究對象的代謝基因多型性…………………….32
第三節、研究對象的單變項及多變項分性……………….34
第四節、研究對象之暴露濃度及代謝基因多型性對受孕所需時間
的交互作用…………………………………………….……38
第伍章、討論
第一節、樣本的代表性及可比性………………………….50
第二節、問卷測量的問題……………………………….…50
第三節、暴露指標評估…………………………………….51
第四節、生育能力測量…………………………………….51
第五節、代謝基因多型性…………………………………52
第六節、研究結果………………………………………….52
第陸章、結論與建議……………………………………….55
參考資料
中文部分…………………………………………………….56
英文部分…………………………………………………….57
附錄
附錄一:研究問卷………………………………………….62
附錄二:有抽血資料各暴露組與各受孕所需時間組之基本資料…..67
圖列
圖1:氯乙烯代謝圖…………………………………………6
圖2:男性工人暴露於氯乙烯單體可能造成的潛在危害結果…13
圖3:樣本選取之流程圖……………………………………..…18
圖4:男性氯乙烯聚合工人其配偶受孕所需時間的測量方式……..23
圖5:暴露組與非暴露組選取時間之起訖點……………………..…23
圖6:受孕所需時間……………………………………………..…39
表列
表1:氯乙烯聚合工人各種職務之暴露分層…………………….24
表2:各暴露組與各受孕所需時間組之基本資料….…………….40
表3:有抽血資料各暴露組與各受孕所需時間組之基本資料…...45
表4:男性聚氯乙烯工人配偶受孕所需時間Cox model 單變項及多變項
受孕比…….………………………………..……….46
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