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N,N-二甲基甲酰胺:来自韩国全国代表性队列研究的致癌性证据。

N,N-dimethylformamide: evidence of carcinogenicity from national representative cohort study in South Korea.

机构信息

Department of Preventive Medicine, Wonju College of Medicine, Yonsei University, 162, Ilsan-dong, Wonju, South Korea.

出版信息

Scand J Work Environ Health. 2019 Jul 1;45(4):396-401. doi: 10.5271/sjweh.3802. Epub 2019 Mar 24.

Abstract

Objective There is limited epidemiological evidence of carcinogenicity on exposure of N,N-dimethylformamide (DMF). This study aimed to identify the possible association between cancer mortality and DMF exposure. Methods A cohort of 11 953 workers exposed to DMF between 1 January 2000 and 31 December 2004 was studied. A urinary metabolite of DMF, N-methylformamide level (UNMFL), was used for exposure assessment. This cohort was matched with the mortality data of the Korean National Statistical Office and followed up for cancer mortality between 2000 and 2011. Standardized mortality ratios (SMR) of the DMF-exposed workers with reference to Korean men were calculated. Adjusted hazard ratios (HRadj; also controlling for age, other carcinogen exposure including hepatitis B and C) were calculated for the workers categorized in three exposure groups with reference to workers with no exposure. Results The HRadj of overall cancer mortality were significantly increased in workers with 7.5-<15 mg/L [HRadj 2.72, 95% confidence interval (CI) 1.09-6.81] and ≥15 mg/L (HRadj 2.41, 95% CI 1.03-5.66) compared with non-exposed workers. Hepatocellular carcinoma mortality (HRadj 3.73, 95% CI 1.05-13.24) of workers with ≥15 mg/L and lung cancer mortality (HRadj 14.36, 95% CI 1.41-146.86) in workers with 7.5-<15 mg/L were significantly increased. Conclusions Workers with high DMF exposure showed increased mortalities for overall, liver, and lung cancer. Our results suggest that DMF causes cancer, especially hepatocellular carcinoma, which is in agreement with earlier studies on liver cancer in animal experiments.

摘要

目的

关于接触 N,N-二甲基甲酰胺(DMF)是否致癌,目前的流行病学证据有限。本研究旨在确定癌症死亡率与 DMF 暴露之间可能存在的关联。

方法

本研究纳入了 11953 名于 2000 年 1 月 1 日至 2004 年 12 月 31 日期间接触 DMF 的工人作为研究对象。使用尿中 DMF 的代谢物 N-甲基甲酰胺水平(UNMFL)进行暴露评估。将该队列与韩国国家统计局的死亡率数据相匹配,并对 2000 年至 2011 年期间的癌症死亡情况进行随访。以韩国男性为参照,计算 DMF 暴露工人的标准化死亡率比值(SMR)。对于暴露于不同水平 DMF 的工人,以无暴露工人为参照,计算调整后的危险比(HRadj;同时控制年龄和包括乙型肝炎和丙型肝炎在内的其他致癌物质暴露情况)。

结果

与非暴露工人相比,暴露于 7.5-<15mg/L(HRadj 2.72,95%置信区间 [CI] 1.09-6.81)和≥15mg/L(HRadj 2.41,95% CI 1.03-5.66)的工人的总体癌症死亡率的 HRadj 显著升高。暴露于≥15mg/L 的工人中肝癌死亡率(HRadj 3.73,95% CI 1.05-13.24)和暴露于 7.5-<15mg/L 的工人中肺癌死亡率(HRadj 14.36,95% CI 1.41-146.86)均显著升高。

结论

高 DMF 暴露工人的总体、肝脏和肺癌死亡率升高。我们的结果表明,DMF 可致癌,尤其是肝癌,这与动物实验中关于肝癌的早期研究结果一致。

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