Kwon Mi Jung, Kang Ho Suk, Choi Hyo Geun, Kim Joo-Hee, Kim Ji Hee, Bang Woo Jin, Yoo Dae Myoung, Lee Na-Eun, Han Kyeong Min, Kim Nan Young, Hong Sangkyoon, Lee Hong Kyu
Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Republic of Korea.
Division of Gastroenterology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Republic of Korea.
Cancers (Basel). 2025 Mar 4;17(5):877. doi: 10.3390/cancers17050877.
BACKGROUND/OBJECTIVES: Proton pump inhibitors (PPIs) are widely used for acid-related gastrointestinal disorders, but their potential association with lung cancer risk and mortality remains underexplored and debated. This study sought to investigate the association between PPI use and lung cancer likelihood and mortality, focusing on the impact of PPI exposure history and duration.
This study utilized data from 6795 lung cancer patients, 27,180 matched controls, and 4257 deceased and 2538 surviving lung cancer patients from the Korean National Health Insurance Service's Health Screening Cohort (2002-2019). Propensity score overlap weighting and logistic regression models were applied to assess the correlations between PPI usage history and duration with lung cancer risk and mortality, while standardized differences ensured balanced baseline characteristics.
Overall, PPI use was modestly associated, with a 19% increased likelihood of lung cancer occurrence (95% confidence intervals (CI): 1.12-1.26). Interestingly, prolonged PPI use (≥30 days) was linked to a 13% reduction in lung cancer incidence (95% CI: 0.80-0.94), particularly in subgroups such as older adults (≥70 years), individuals with gastroesophageal reflux disease (GERD) or hypertension, and those with low alcohol consumption. Conversely, overall PPI usage was linked with a 36% increased mortality likelihood among lung cancer patients (95% CI: 1.20-1.55), with prolonged use further correlating with a 27% higher mortality risk (95% CI: 1.05-1.53), especially in high-risk subgroups, including smokers, underweight individuals, and those with hypercholesterolemia or GERD.
These findings may suggest a complex and context-dependent relationship between PPI use and lung cancer outcomes, emphasizing the need for individualized risk assessments and careful prescribing practices.
背景/目的：质子泵抑制剂（PPIs）被广泛用于治疗与酸相关的胃肠道疾病，但其与肺癌风险和死亡率之间的潜在关联仍未得到充分研究和讨论。本研究旨在探讨PPIs使用与肺癌发生可能性及死亡率之间的关联，重点关注PPIs暴露史和使用时长的影响。
本研究利用了来自韩国国民健康保险服务健康筛查队列（2002 - 2019年）的6795例肺癌患者、27180例匹配对照以及4257例已故肺癌患者和2538例存活肺癌患者的数据。采用倾向得分重叠加权法和逻辑回归模型来评估PPIs使用史和使用时长与肺癌风险及死亡率之间的相关性，同时通过标准化差异确保基线特征的平衡。
总体而言，使用PPIs与肺癌发生可能性适度相关，肺癌发生可能性增加19%（95%置信区间（CI）：1.12 - 1.26）。有趣的是，长期使用PPIs（≥30天）与肺癌发病率降低13%相关（95%CI：0.80 - 0.94），特别是在老年人群（≥70岁）、患有胃食管反流病（GERD）或高血压的个体以及低酒精摄入量人群等亚组中。相反，总体PPIs使用与肺癌患者死亡率增加36%相关（95%CI：1.20 - 1.55），长期使用进一步与死亡率风险升高27%相关（95%CI：1.05 - 1.53），尤其是在包括吸烟者、体重过轻个体以及患有高胆固醇血症或GERD的人群等高风险亚组中。
这些发现可能表明PPIs使用与肺癌结局之间存在复杂且依赖于背景的关系，并强调了进行个体化风险评估和谨慎处方的必要性。
