Choi Hyo Geun, Lee Hong Kyu, Kang Ho Suk, Lim Hyun, Kim Joo-Hee, Kim Ji Hee, Kim Nan Young, Cho Seong-Jin, Nam Eun Sook, Min Kyueng-Whan, Kwon Mi Jung
Department of Otorhinolaryngology-Head & Neck Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Korea.
Department of Thoracic and Cardiovascular Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Korea.
Pharmaceuticals (Basel). 2022 Apr 22;15(5):517. doi: 10.3390/ph15050517.
Although safety concerns regarding proton pump inhibitor (PPI)/H2-receptor antagonists (H2RA) in the incident esophageal cancer have been raised, the Asian-based report is unclear. We investigated the estimated likelihood of incident esophageal cancer—its mortality depending on prior history of PPI/H2RA use—and gastroesophageal reflux disease (GERD) in Koreans. Using the Korean National Health Insurance Service-Health Screening Cohort data (2002−2015), a case−control study was retrospectively conducted, including 811 patients with incident esophageal cancer and 3244 controls matched with sex, age, income, and residence. Propensity score overlap weighting was adjusted to balance the baseline covariates. Overlap propensity score-weighted logistic regression analyses were assessed to determine associations of the prior exposure of PPI/H2RA (current vs. past) and the medication duration (<30-, 30−90-, vs. ≥90-days) with incident esophageal cancer and its mortality among the total participants or those with/without the GERD episodes, after adjusting for multiple covariates including PPI/H2RA. The current exposure to either PPI or H2RA showed higher odds for incident esophageal cancer than the nonuser group ([13.23; 95%CI 10.25−17.06] and [4.34; 95%CI 3.67−5.14], respectively), especially in all adults over the age of 40 years without GERD. Both current and past exposures to PPI showed a decreased probability of mortality compared with those of the nonuser group ([0.62; 95%CI 0.45−0.86] and [0.41; 95%CI 0.25−0.67], respectively). However, current or past exposure to H2RA harbored the mutually different likelihoods for mortality depending on the presence of GERD and old age. This study carefully speculates on the possible link between PPI/H2RA and incident esophageal cancer in the Korean population. Mortality appears to be affected by certain risk factors depending on drug types, exposure history, old age, and the presence of GERD.
尽管有人提出了关于质子泵抑制剂（PPI）/H2受体拮抗剂（H2RA）与食管癌发病之间的安全性问题，但基于亚洲的报告并不明确。我们调查了韩国人患食管癌的估计可能性——其死亡率取决于PPI/H2RA的既往使用史——以及胃食管反流病（GERD）。利用韩国国民健康保险服务健康筛查队列数据（2002 - 2015年），进行了一项回顾性病例对照研究，包括811例食管癌患者和3244例按性别、年龄、收入和居住地匹配的对照。采用倾向得分重叠加权法来平衡基线协变量。在调整包括PPI/H2RA在内的多个协变量后，进行重叠倾向得分加权逻辑回归分析，以确定PPI/H2RA的既往暴露情况（当前使用与过去使用）以及用药持续时间（<30天、30 - 90天、≥90天）与所有参与者或有/无GERD发作的参与者中食管癌发病及其死亡率之间的关联。当前使用PPI或H2RA的人群患食管癌的几率高于未使用者组（分别为[13.23；95%置信区间10.25 - 17.06]和[4.34；95%置信区间3.67 - 5.14]），尤其是在所有40岁以上无GERD的成年人中。与未使用者组相比，当前和过去使用PPI均显示死亡率降低（分别为[0.62；95%置信区间0.45 - 0.86]和[0.41；95%置信区间0.25 - 0.67]）。然而，当前或过去使用H2RA根据GERD的存在情况和年龄不同，死亡率的可能性也不同。本研究仔细推测了韩国人群中PPI/H2RA与食管癌发病之间可能的联系。死亡率似乎受某些风险因素影响，这些因素取决于药物类型、暴露史、年龄以及GERD的存在情况。
