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研究生:宋姿頤
研究生(外文):Tzu-I Sung
論文名稱:電子業女工罹患乳癌與子代生殖影響之流行病學研究
論文名稱(外文):An Epidemiological Study for Breast Cancer among Female Electronics Workers and Reproductive Outcomes in Offspring
指導教授:王榮德王榮德引用關係
指導教授(外文):Jung-Der Wang
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文出版年:2008
畢業學年度:96
語文別:英文
論文頁數:58
中文關鍵詞:乳癌癌症心臟缺陷孩童電子業白血病先天性畸形下一代有機溶劑標準化發生率比三氯乙烯
外文關鍵詞:Breast cancerCancerCardiac defectsChildrenElectronicsLeukemiaMalformationOffspringOrganic solventsStandardized incidence ratioTrichloroethylene
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背景
危害廢棄廠址一直是許多國家所關心的議題,臺灣於1994年爆發一件重大污染案件,桃園某電子工廠因過去不當傾倒有機溶劑,污染廠區內地下水及土壤。此廠興建於1970年,於1991年關閉。污染案件疑似與職業性癌症有關,本研究欲瞭解此曾任職於此工廠女工所發生之乳癌風險是否增加。由於父母親受孕前後期暴露與子代生殖影響之文獻實屬有限,本研究亦探討母親受孕期前後期暴露有機溶劑與其子代第一胎罹癌風險之關係,及同廠男工所生子代之嬰兒缺陷死亡率。
方法
1973年至1997年之勞工保險資料顯示,總共有63,982名女工曾受雇於此工廠,連結衛生署癌症登記檔來確立癌症發生個案,以一般大眾癌症發生率作為對照,計算出不同類型癌症之標準化發生率比。
將母親身份證字號與子代之出生登記與癌症登記檔作連結,串聯出40,647名第一胎活產且單產的出生兒作為研究族群,於1979年至2001年間有47名孩童罹患癌症。子代「受孕前後期暴露」的定義為受精前後三個月內母親曾在此工廠受雇,「未暴露」則為不在前述關鍵期受雇的母親。在控制母親年紀、教育程度、孩童性別與出生年代之下,基於波以松統計分析模式計算出癌症發生率比。
針對同廠男工所生嬰兒之缺陷死亡分析,以7,545位父親的身份證字號連結子代之出生登記與死因資料檔,於1980年至1992年間串聯出14,453名活產出生兒與83名一歲內死亡之嬰兒。子代「受孕前期暴露」的定義為受精前三個月內父親曾在此工廠受雇,「未暴露」則為不在前述關鍵期受雇的父親。剔除母親於懷孕期間在同工作環境暴露(同工廠受雇)之442名孩童後,同時控制嬰兒性別、胎次、多胎與出生年代,及父母親生產年齡和教育程度之下,以波以松統計分析模式計算出嬰兒死亡率比。
結果
調整年代、年齡之後,286位乳癌個案之標準化發生率比值趨近1,以1974年(法規開始嚴格控管有機溶劑使用時)作為分層後發現,最早受雇於1974年前的女工,乳癌標準化發生率比增加至1.38(95%信賴區間為1.11至1.70),然而1974年後才開始受雇的女工並無發現類似結果。當考慮年資並以10年工作期作為分層時,工作期達10年之女工乳癌標準化發生率比上升至1.62。在1974年之前第一次入廠工作的女工年紀較輕,且工作期間也較長。與工人訪談之質性研究調查顯示,早期電子業曾大量使用三氯乙烯作為金屬脫脂,勞動檢查記錄亦佐證此工廠曾使用多種有機溶劑,因此在1974年法規施行之前的工人,很有可能暴露於短期高劑量的氯化烷烯類物質。然而本研究並無發現其他癌症有增加的情形。
針對母親受孕前後期暴露之11名罹患癌症孩童,其總惡性腫瘤發生率比值上升至2.26(95%信賴區間為1.12至4.54),此外此癌症發生率比值的上升也與母親教育程度低於10年有關,分別為小學(率比為3.05;95%信賴區間為1.26至4.94)和中學(率比為2.49;95%信賴區間為1.17至12.55)。暴露組孩童之白血病發生率比值(3.83)更是顯著增加,95%信賴區間為1.17 至12.55。
關於父親受孕前期暴露,總計24名嬰兒死亡個案,受孕前期暴露組嬰兒死亡率相較於非暴露組之比為2.71(95%信賴區間為1.58至4.64)。母親生產年齡小於20歲,父親教育程度低於10年,及多產次的嬰兒具較高之死亡風險。針對27名因先天性缺陷死亡的嬰兒作分析,發現相較於非暴露組孩童,父親於受孕前期暴露所生之孩童,先天性畸形死亡率比值(3.69)及心臟缺陷死亡率比值(4.97)明顯增加,95%信賴區間分為1.26 至10.75及1.55至15.89。
結論
此工廠女工可能暴露於三氯乙烯及/或混合之有機溶劑,於1974年前開始受雇者具有較高之乳癌發生風險;受孕前後期受雇之母親,很有可能因暴露有機溶劑導致孩童癌症發生率增加,特別是白血病;受孕前期受雇之同工廠父親,有可能因暴露有機溶劑導致嬰兒先天性畸形死亡率上升,尤其在心臟缺陷方面。然而孩童癌症或死亡個案數少,可能會限制研究之外推性。
Background
In 1994, a hazardous waste site, polluted by the dumping of solvents from a former electronics factory, was discovered in Taoyuan, Taiwan. This subsequently emerged as a serious case of contamination through chlorinated hydrocarbons with suspected occupational cancer. There is limited evidence on the hypothesis that maternal occupational exposure near conception increases the risk of cancer in offspring, and the association between paternal occupational exposure during preconception and infant mortality from congenital malformation.
The objectives of this study were to determine if there was any increased risk of breast cancer among female workers in a 23-year follow-up period, to investigate whether women employed in this electronics factory increases childhood cancer among first live born singletons, and to determine if such an association existed among male workers employed in this electronics factory.
Methods
A total of 63,982 female workers were retrospectively recruited from the database of the Bureau of Labor Insurance (BLI) covering the period 1973-1997; the data were then linked with data, up to 2001, from the National Cancer Registry at the Taiwanese Department of Health, from which standardized incidence ratios (SIRs) for different types of cancer were calculated as compared to the general population.
We linked the databases of birth registration and labor insurance, and national cancer registry, which identified 40,647 female workers ever employed in this factory who gave 40,647 first live born singletons, and 47 of them developed cancers during 1979-2001. Mothers employed in this factory during their periconceptional periods (three months before and after conception) were considered as exposed and compared with those not employed during the same periods. Poisson regression model was constructed to adjust for potential confounding by maternal age, education, sex, and year of birth.
We also inked the databases of birth registration, labor insurance, and national death registry, identified 7,545 male workers ever employed in this factory with 14,453 live born children and 83 deaths in the first year. Fathers employed in this factory during their preconceptional periods (three months prior to the conception) were considered as exposed compared with those not employed during the same periods. After excluding 442 children with potential maternal exposure from the same workplace, Poisson regression models were constructed to adjust for potential confounding by child’s gender, parity, multiple births, year of birth, parental age at delivery and educational levels.
Results
There were a total of 286 cases of breast cancer, and after adjustment for calendar year and age, the SIR was close to 1. When stratified by the year 1974 (the year in which the regulations on solvent use were promulgated), the SIR of the cohort of workers who were first employed prior to 1974 increased to 1.38 [95% confidence interval (CI): 1.11-1.70]. No such trend was discernible for workers employed after 1974. When 10 years of employment was considered, there was a further increase in the SIR for breast cancer, to 1.62. Those workers with breast cancer who were first employed prior to 1974 were employed at a younger age and for a longer period. Previous qualitative studies of interviews with the workers, corroborated by inspection records, showed a short-term high exposure to chlorinated alkanes and alkenes, particularly trichloroethylene before 1974. There were no similar findings on other types of cancer.
Based on 11 exposed cases, the rate ratio (RR) of all malignant neoplasms was increased to 2.26 (95% CI: 1.12-4.54) among children whose mothers worked in this factory during periconceptional periods. The RRs were associated with six years or less (RR= 3.05; 95% CI: 1.20-7.74) and seven to nine years (RR= 2.49; 95% CI: 1.26-4.94) of education compared with ten years or more. An increased association was also found between childhood leukemia and exposed pregnancies (RR= 3.83; 95% CI: 1.17-12.55).
The RR for infant mortality was increased to 2.71 [95% confidence interval (CI): 1.58‐4.64] among live born children whose fathers worked in this factory during preconception. Maternal delivering age less than 20 years, fathers with less than 10 years of education, and multiple births were associated with increased risks of infant mortality. When limited to 27 deaths with congenital malformation, Poisson regression model showed an increased risk for exposed pregnancies (RR = 3.69; 95% CI: 1.26-10.75), especially among cardiac defects (RR = 4.97; 95% CI: 1.55-15.89).
Conclusions
Female workers with exposure to trichloroethylene and/or mixture of solvents, first employed prior to 1974, may have an excess risk of breast cancer. Our study suggests that maternal occupation with potential exposure to organic solvents during periconception might increase risks of childhood cancers, especially for leukemia. Besides, paternal occupational exposures, possibly organic solvents during preconception, might increase infant mortality and deaths due to congenital malformation, especially for cardiac defects. However, the small numbers of this study limited its generalizability.
Table of Contents I
List of Tables IV
List of Figures VI
中文摘要 VII
Abstract X
1 Background 1
1.1 Part Ⅰ 1
1.2 Part Ⅱ 2
1.3 Part Ⅲ 2
2 Objectives 4
3 Study Design 5
3.1 Part Ⅰ 5
3.1.1 The Cohort of Female Workers 5
3.1.2 Employment 6
3.1.3 Latency 6
3.1.4 Exposure Assessment 7
3.1.5 Statistical Analysis 8
3.2 Part Ⅱ 8
3.2.1 Offspring Cohort of Female Workers 8
3.2.2 Maternal Employment 9
3.2.3 Vital Status 9
3.2.4 Exposure Assessment 10
3.2.5 Statistical Analyses 10
3.3 Part Ⅲ 10
3.3.1 Offspring Cohort of Male Workers 10
3.3.2 Paternal Employment 11
3.3.3 Vital Status 11
3.3.4 Exposure Assessment 12
3.3.5 Statistical Analyses 12
4 Results 14
4.1 Part Ⅰ 14
4.2 Part Ⅱ 15
4.3 Part Ⅲ 16
5 Discussion 32
5.1 Part Ⅰ 32
5.2 Part Ⅱ 35
5.3 Part Ⅲ 39
6 Conclusions 48
6.1 Part Ⅰ 48
6.2 Part Ⅱ 48
6.3 Part Ⅲ 49
7 References 50
8 Appendix 59
8.1 Manuscript accepted 59
8.1.1 Appendix 1 59
8.1.2 Appendix 2 59
8.2 Submitted manuscripts being revised 59
8.2.1 Appendix 3 59
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