2020年由于N-亚硝基二甲胺杂质的存在，雷尼替丁，作为广泛应用的最常见的组胺H2受体拮抗剂（H2RA），被召回。鉴于世界范围内对这种药物的暴露，与摄入已知致癌物质相关的癌症发生潜在风险成为重要的流行病学关切。本研究集使用美国、英国、德国、西班牙、法国、韩国和台湾的3个医疗保险索赔和9个电子健康记录数据库进行了新用户主动比较的国际网络队列研究。大规模倾向性评分匹配用于最小化观察到的协变量与阴性对照结果的混杂。经验校准用于解释未观察到的混杂。所有数据库都映射到一个共同的数据模型。使用随机效应的荟萃分析将数据库特定的估计值进行组合。研究对象包括在1986年1月至2020年12月期间使用H2RA超过30天、具有1年间歇期的至少20岁的无癌症史的个体。数据由2021年4月至9月进行分析。主要暴露是雷尼替丁与其他H2RA（法莫替丁、马法替丁、硝替丁和罗沙替丁）的使用。主要结局是任何癌症，不包括非黑色素瘤皮肤癌。次要结局包括所有癌症，除甲状腺癌外的16种癌症亚型以及全因死亡率。在11个数据库的1,183,999名个体中，确定了909,168名个体（平均年龄为56.1岁；507,316名（55.8%）为女性）作为雷尼替丁的新用户，274,831名个体（平均年龄为58.0岁；145,935名（53.1%）为女性）作为其他H2RA的新用户。雷尼替丁用户的癌症发病率为1000人年14.30次事件，而其他H2RA用户为1000人年15.03次事件。经过倾向性评分匹配后，与其他H2RA用户相比，雷尼替丁的癌症风险相似（发病率：1000人年15.92次事件对1000人年15.65次事件；经校准的荟萃分析危险比为1.04；95% CI，0.97-1.12）。在校准后，雷尼替丁使用与任何次要结局之间未发现显著关联。在该队列研究中，雷尼替丁使用与其他H2RA使用相比，并未增加癌症风险。需要进一步研究雷尼替丁与癌症发展的长期关联。

Ranitidine, the most widely used histamine-2 receptor antagonist (H2RA), was withdrawn because of N-nitrosodimethylamine impurity in 2020. Given the worldwide exposure to this drug, the potential risk of cancer development associated with the intake of known carcinogens is an important epidemiological concern.To examine the comparative risk of cancer associated with the use of ranitidine vs other H2RAs.This new-user active comparator international network cohort study was conducted using 3 health claims and 9 electronic health record databases from the US, the United Kingdom, Germany, Spain, France, South Korea, and Taiwan. Large-scale propensity score (PS) matching was used to minimize confounding of the observed covariates with negative control outcomes. Empirical calibration was performed to account for unobserved confounding. All databases were mapped to a common data model. Database-specific estimates were combined using random-effects meta-analysis. Participants included individuals aged at least 20 years with no history of cancer who used H2RAs for more than 30 days from January 1986 to December 2020, with a 1-year washout period. Data were analyzed from April to September 2021.The main exposure was use of ranitidine vs other H2RAs (famotidine, lafutidine, nizatidine, and roxatidine).The primary outcome was incidence of any cancer, except nonmelanoma skin cancer. Secondary outcomes included all cancer except thyroid cancer, 16 cancer subtypes, and all-cause mortality.Among 1 183 999 individuals in 11 databases, 909 168 individuals (mean age, 56.1 years; 507 316 [55.8%] women) were identified as new users of ranitidine, and 274 831 individuals (mean age, 58.0 years; 145 935 [53.1%] women) were identified as new users of other H2RAs. Crude incidence rates of cancer were 14.30 events per 1000 person-years (PYs) in ranitidine users and 15.03 events per 1000 PYs among other H2RA users. After PS matching, cancer risk was similar in ranitidine compared with other H2RA users (incidence, 15.92 events per 1000 PYs vs 15.65 events per 1000 PYs; calibrated meta-analytic hazard ratio, 1.04; 95% CI, 0.97-1.12). No significant associations were found between ranitidine use and any secondary outcomes after calibration.In this cohort study, ranitidine use was not associated with an increased risk of cancer compared with the use of other H2RAs. Further research is needed on the long-term association of ranitidine with cancer development.