Collingwood K W, Pasternack B S, Shore R E
J Natl Cancer Inst. 1987 Jun;78(6):1127-36.
An industry-wide retrospective cohort mortality study was conducted on 6,152 chemical workers (2,460 exposed and 3,692 nonexposed) engaged in chloromethyl ether manufacture at 7 major U.S. companies between 1948 and 1980. A previous study at 6 companies from 1948 through 1972 reported excess respiratory cancer (RC) mortality and significant exposure-response relationships in exposed workers at 1 company (company 2). The present study, which extended follow-up of an additional 7 years for companies 1-6 and included company 7 for follow-up from 1953 through 1980, found excess RC mortality in exposed workers at company 2 [observed (Obs) = 32, standardized mortality ratio (SMR) = 430] and company 7 (Obs = 9, SMR = 603). External comparisons of RC mortality at both companies showed significant exposure-response relationships with respect to cumulative time-weighted exposure. At company 2, where the greatest number of RC deaths occurred, external comparisons showed that RC risk remained constant in relation to age at first exposure and decreased with increasing time since last exposure. With the use of Mantel-Haenszel and relative risk (RR) regression methods, internal comparisons at company 2 demonstrated significant findings of increasing RR with cumulative duration of exposure and cumulative time-weighted exposure and with decreasing time since last exposure. No association was found between RR and age at first exposure. An interesting finding was a significant negative interaction between cumulative time-weighted exposure and age at risk. The best-fitting logistic regression model for the exposed group predicted RR at 2.79 (95% confidence interval = 1.66-4.69) for workers with the mean cumulative exposure score of the 32 RC deaths (lagged by 6 yr) compared with those with negligible exposure (assuming mean age at risk of the RC deaths, 51 years old, and time since last exposure held constant). Qualitative assessment of the results suggests that chloromethyl ether exposure affects both an early as well as a late stage of a putative multistage respiratory malignant process.
对1948年至1980年间美国7家主要公司从事氯甲醚生产的6152名化学工人（2460名暴露工人和3692名非暴露工人）进行了一项全行业回顾性队列死亡率研究。此前一项对6家公司1948年至1972年期间的研究报告称，有一家公司（公司2）的暴露工人中呼吸道癌（RC）死亡率过高，且存在显著的暴露-反应关系。本研究对公司1至6进行了另外7年的随访，并纳入了公司7从1953年至1980年的随访数据，发现公司2（观察到的死亡人数[Obs]=32，标准化死亡率比[SMR]=430）和公司7（Obs=9，SMR=603）的暴露工人中存在RC死亡率过高的情况。两家公司RC死亡率的外部比较显示，就累积时间加权暴露而言，存在显著的暴露-反应关系。在RC死亡人数最多的公司2，外部比较显示，RC风险与首次暴露时的年龄保持恒定，且随着上次暴露后时间的增加而降低。使用Mantel-Haenszel和相对风险（RR）回归方法，公司2的内部比较显示，RR随着暴露累积持续时间、累积时间加权暴露以及上次暴露后时间的减少而增加，结果具有显著性。未发现RR与首次暴露时的年龄之间存在关联。一个有趣的发现是累积时间加权暴露与风险年龄之间存在显著的负交互作用。暴露组的最佳拟合逻辑回归模型预测，与暴露可忽略不计的工人相比（假设RC死亡的平均风险年龄为51岁，上次暴露后时间保持不变），32例RC死亡（滞后6年）的平均累积暴露得分的工人的RR为2.79（95%置信区间=1.66-4.69）。对结果的定性评估表明，氯甲醚暴露会影响假定的多阶段呼吸道恶性病变过程的早期和晚期。
