Steenland Kyle, Whelan Elizabeth, Deddens James, Stayner Leslie, Ward Elizabeth
National Institute for Occupational Safety and Health (NIOSH), Cincinnati, Ohio 30322, USA.
Cancer Causes Control. 2003 Aug;14(6):531-9. doi: 10.1023/a:1024891529592.
Ethylene oxide (ETO) is a sterilant gas considered to be a human carcinogen, due primarily to excess hematopoietic cancer in exposed cohorts. ETO causes mammary tumors in mice, and has been associated with breast cancer incidence in one small epidemiologic study.
We have studied breast cancer incidence in a cohort of 7576 women employed for at least one year and exposed for an average 10.7 years while working in commercial sterilization facilities. Breast cancer incidence (n = 319) was ascertained via interview, death certificates, cancer registries, and medical records. Interviews were obtained for 68% of the cohort.
The standardized incidence ratio (SIR) for incident breast cancer in the whole cohort using external referent rates (SEER) was 0.87 (0.77-0.97). The SIR for those in the top quintile of cumulative exposure, with a 15 year lag, was 1.27 (0.94-1.69), with a positive trend of increasing SIR with increasing exposure (p = 0.002). SIRs are underestimated because breast cancer incidence in the whole cohort was under-ascertained, due to incomplete response and lack of complete coverage by state cancer registries. In internal nested case-control analyses of those with interviews (complete cancer ascertainment), controlling for reproductive risk factors, a positive exposure-response was found with the log of cumulative exposure with a 15-year lag (p = 0.0005). The odds ratio by quintile of cumulative exposure were 1.00 (0 exposure due to 15 year lag), 1.06, 0.99, 1.24, 1.42, and 1.87.
Our data suggest that ETO is associated with breast cancer, but a causal interpretation is weakened due to some inconsistencies in exposure-response trends and possible biases due to non-response and incomplete cancer ascertainment.
环氧乙烷（ETO）是一种杀菌气体，主要因其使暴露人群患造血系统癌症的比例过高而被视为人类致癌物。ETO可导致小鼠患乳腺肿瘤，并且在一项小型流行病学研究中已发现其与乳腺癌发病率有关。
我们对一组7576名女性的乳腺癌发病率进行了研究，这些女性在商业消毒设施工作至少一年，平均暴露时间为10.7年。通过访谈、死亡证明、癌症登记处和医疗记录确定乳腺癌发病率（n = 319）。对该队列中68%的人进行了访谈。
使用外部参考率（监测、流行病学与最终结果，SEER）计算，整个队列中乳腺癌的标准化发病比（SIR）为0.87（0.77 - 0.97）。累积暴露处于最高五分位数且有15年滞后的人群的SIR为1.27（0.94 - 1.69），呈现出SIR随暴露增加而上升的正相关趋势（p = 0.002）。由于整个队列中乳腺癌发病率确定不足，SIR被低估了，原因是应答不完整以及州癌症登记处缺乏全面覆盖。在对有访谈记录者（癌症确诊完整）进行的内部巢式病例对照分析中，在控制生殖风险因素的情况下，发现累积暴露对数与15年滞后存在正暴露 - 反应关系（p = 0.0005）。累积暴露五分位数的比值比分别为1.00（因15年滞后暴露为0）、1.06、0.99、1.24、1.42和1.87。
我们的数据表明ETO与乳腺癌有关，但由于暴露 - 反应趋势存在一些不一致以及无应答和癌症确诊不完整可能导致的偏差，因果关系的解释力度有所减弱。
