Haselkorn Tmirah, Whittemore Alice S, Udaltsova Natalia, Friedman Gary D
Division of Epidemiology, Department of Health Research & Policy, Stanford University School of Medicine, Stanford, California, USA.
Drug Saf. 2006;29(1):67-77. doi: 10.2165/00002018-200629010-00005.
Chloral hydrate, used as a hypnosedative in adults and children, has been shown to be genotoxic and carcinogenic in animal studies. We investigated the potential causal association between chloral hydrate exposure and cancer risk in humans.
Cancer incidence was previously determined via biennial screening analyses of the 215 most commonly used drugs between 1976 and 1998 for a cohort of 143,574 outpatients at Kaiser Permanente who had prescriptions filled between 1969 and 1973. Among users of chloral hydrate, statistically significant elevations in standardised morbidity ratios were observed during various years for cancer at five anatomical sites, including the lung, stomach, prostate, skin melanoma and mouth floor. In this analysis, these associations were investigated using: (i) a dose-response analysis among exposed subjects; and (ii) a two-stage design with exposed and non-exposed persons.
There was evidence of an increasing risk of prostate cancer with increasing number of dispensings of chloral hydrate, which persisted after controlling for benign prostatic hypertrophy, vasectomy and obesity; however, the trend was not statistically significant. There was no evidence of a dose-response relationship between chloral hydrate and risk of any of the other four cancers. In the two-stage design, analyses comparing exposed and unexposed subjects showed no increased risk of cancer after controlling for confounding variables; however, the data were suggestive for prostate cancer, where the increased risk associated with chloral hydrate exposure after adjustment for confounding variables persisted. No dose-response relationship was seen for any of the other four cancer sites.
To our knowledge, this is the first study to examine the relationship between chloral hydrate exposure and cancer risk in humans. There was no persuasive evidence to support a causal relationship between chloral hydrate exposure in humans and the development of cancer. However, statistical power was low for weak associations, particularly for some of the individual cancer sites. Although animal data using much higher doses of chloral hydrate have demonstrated its genotoxicity and carcinogenicity, the effects of chloral hydrate in humans are still uncertain.
水合氯醛在成人和儿童中用作催眠镇静剂，动物研究表明其具有遗传毒性和致癌性。我们调查了水合氯醛暴露与人类癌症风险之间的潜在因果关系。
先前通过对1976年至1998年间215种最常用药物进行两年一次的筛查分析，确定了1969年至1973年间在凯撒医疗机构有处方配药的143,574名门诊患者队列中的癌症发病率。在水合氯醛使用者中，在不同年份观察到五个解剖部位的癌症标准化发病比有统计学意义的升高，包括肺癌、胃癌、前列腺癌、皮肤黑色素瘤和口底癌。在本分析中，使用以下方法研究这些关联：(i) 暴露受试者中的剂量反应分析；(ii) 暴露和未暴露人群的两阶段设计。
有证据表明，随着水合氯醛配药次数的增加，前列腺癌风险增加，在控制良性前列腺增生、输精管切除术和肥胖后这种情况仍然存在；然而，该趋势无统计学意义。没有证据表明水合氯醛与其他四种癌症中的任何一种风险之间存在剂量反应关系。在两阶段设计中，比较暴露和未暴露受试者的分析表明，在控制混杂变量后癌症风险没有增加；然而，数据提示前列腺癌存在这种情况，调整混杂变量后与水合氯醛暴露相关的风险增加仍然存在。其他四个癌症部位均未观察到剂量反应关系。
据我们所知，这是第一项研究水合氯醛暴露与人类癌症风险之间关系的研究。没有有说服力的证据支持人类水合氯醛暴露与癌症发生之间存在因果关系。然而，对于弱关联，尤其是某些个别癌症部位，统计效力较低。尽管使用高得多剂量水合氯醛的动物数据已证明其遗传毒性和致癌性，但水合氯醛对人类的影响仍不确定。
