German Center for Neurodegenerative Diseases (DZNE) e. V., Bonn; AOK Research Institute (WIdO), Berlin; Federal Institute for Drugs and Medical Devices (BfArM), Bonn; Center for Translational Medicine, University Hospital Bonn.
Dtsch Arztebl Int. 2021 May 28;118(21):357-362. doi: 10.3238/arztebl.m2021.0129.
N-Nitrosodimethylamine (NDMA), classified as a probable human carcinogen, has been found as a contaminant in the antihypertensive drug valsartan. Potentially carcinogenic effects associated with the consumption of NDMAcontaminated valsartan have not yet been analyzed in large-scale cohort studies. We therefore carried out the study reported here to explore the association between NDMA-contaminated valsartan and the risk of cancer.
This cohort study was based on longitudinal routine data obtained from a large German statutory health insurance provider serving approximately 25 million insurees. The cohort comprised patients who had filled a prescription for valsartan in the period 2012-2017. The endpoint was an incident diagnosis of cancer. Hazard ratios (HR) for cancer in general and for certain specific types of cancer were calculated by means of Cox regression models with time-dependent variables and adjustment for potential confounders.
A total of 780 871 persons who had filled a prescription for valsartan between 2012 and 2017 were included in the study. There was no association between exposure to NDMA-contaminated valsartan and the overall risk of cancer. A statistically significant association was found, however, between exposure to NDMA-contaminated valsartan and hepatic cancer (adjusted HR 1.16; 95% confidence interval [1.03; 1.31]).
These findings suggest that the consumption of NDMA-contaminated valsartan is associated with a slightly increased risk of hepatic cancer; no association was found with the risk of cancer overall. Close observation of the potential long-term effects of NDMA-contaminated valsartan seems advisable.
N-亚硝基二甲胺（NDMA）被归类为可能的人类致癌物质，已在降压药缬沙坦中发现作为污染物。与消费 NDMA 污染的缬沙坦相关的潜在致癌作用尚未在大规模队列研究中进行分析。因此，我们进行了本报告中所述的研究，以探索 NDMA 污染的缬沙坦与癌症风险之间的关联。
这项队列研究基于从一家为约 2500 万被保险人提供服务的大型德国法定健康保险公司获得的纵向常规数据。该队列包括在 2012-2017 年期间开缬沙坦处方的患者。终点是癌症的确诊诊断。通过具有时间依赖性变量的 Cox 回归模型和对潜在混杂因素的调整，计算出一般癌症和某些特定类型癌症的癌症风险的危害比（HR）。
共有 780871 名在 2012 年至 2017 年间开缬沙坦处方的人被纳入研究。接触 NDMA 污染的缬沙坦与癌症总体风险之间没有关联。然而，接触 NDMA 污染的缬沙坦与肝癌之间存在统计学上显著的关联（调整后的 HR 为 1.16；95%置信区间 [1.03；1.31]）。
这些发现表明，消费 NDMA 污染的缬沙坦与肝癌风险略有增加有关；与癌症总体风险无关。似乎需要密切观察 NDMA 污染的缬沙坦的潜在长期影响。
