Background/Objectives: The association between gastroesophageal reflux disease (GERD) and extraesophageal malignancies remains unclear. This study aimed to systematically evaluate the relationship between GERD and these cancers. Methods: PubMed, Embase, Scopus, Cochrane Library, and Web of Science were searched for studies reporting risk estimates—risk ratios (RRs), odds ratios (ORs), hazard ratios (HRs), or standardized incidence ratios (SIRs)—of GERD and extraesophageal malignancies. Mendelian randomization (MR) studies with available risk estimates and 95% confidence intervals (CIs) were also included. Pooled estimates with 95% CIs were calculated using a random-effects model. Results: As of 21 May 2025, a total of 37 studies were included in the analysis. GERD was significantly associated with an increased risk of several extraesophageal malignancies, including pharyngeal cancer (pooled RR = 2.04; 95% CI: 1.38–3.02), with a particularly high risk observed for hypopharyngeal cancer (RR = 2.95; 95% CI: 1.99–4.37; I2= 60.24%). Elevated risks were also identified for laryngeal cancer (RR = 2.23; 95% CI: 1.41–3.52) and lung cancer (RR = 1.20; 95% CI: 1.01–1.42). No significant association was found between GERD and colorectal cancer (RR = 1.19; 95% CI: 0.68–2.09), and findings regarding oral cancer were inconsistent across studies. Six MR studies confirmed a positive causal relationship between GERD and lung cancer, while one MR study suggested a potential causal association with oral cancer and another with pancreatic cancer. Conclusions: Our findings suggest that GERD may be a significant risk factor for pharyngeal, laryngeal and lung cancers. Appropriate evaluation and surveillance in patients with GERD may be warranted.
背景/目的：胃食管反流病（GERD）与食管外恶性肿瘤之间的关联尚不明确。本研究旨在系统评估GERD与这些癌症之间的关系。方法：检索PubMed、Embase、Scopus、Cochrane Library和Web of Science数据库中报告GERD与食管外恶性肿瘤风险估计值（风险比[RR]、比值比[OR]、风险比[HR]或标准化发病率[SIR]）的研究。同时纳入具有可用风险估计值及95%置信区间（CI）的孟德尔随机化（MR）研究。采用随机效应模型计算合并估计值及95% CI。结果：截至2025年5月21日，共纳入37项研究进行分析。GERD与多种食管外恶性肿瘤风险增加显著相关，包括咽癌（合并RR=2.04；95% CI：1.38–3.02），其中下咽癌风险尤为突出（RR=2.95；95% CI：1.99–4.37；I²=60.24%）。喉癌（RR=2.23；95% CI：1.41–3.52）和肺癌（RR=1.20；95% CI：1.01–1.42）风险亦显著升高。GERD与结直肠癌无显著关联（RR=1.19；95% CI：0.68–2.09），而口腔癌的研究结果在不同研究间存在不一致性。六项MR研究证实GERD与肺癌存在正向因果关系，一项MR研究提示其与口腔癌可能存在因果关联，另一项研究则提示与胰腺癌存在潜在因果关联。结论：本研究提示GERD可能是咽癌、喉癌和肺癌的重要风险因素。对GERD患者进行适当评估与监测具有必要性。
肿瘤(癌症)患者之家