胃食管反流病（GERD）是一种常见疾病，其特征是胃内容物反流到食管。尽管 GERD 在世界范围内广泛流行，但 GERD 与各种癌症风险之间的因果关系尚未完全确定，过去的医学研究常常低估或忽视这种关系。本研究进行了孟德尔随机化 (MR) 来调查 GERD 与 19 之间的因果关系不同的癌症。我们利用了来自 129,080 名 GERD 患者和 473,524 名对照者的数据，以及从英国生物银行和各种全基因组关联研究 (GWAS) 联盟获得的癌症相关数据。与 GERD 相关的单核苷酸多态性 (SNP) 被用作工具变量，利用逆方差加权、加权中位数和 MR-Egger 等方法来解决潜在的多效性和混杂因素。GERD 与九种癌症的较高风险显着相关。即使在调整了所有已知的风险因素（包括吸烟、饮酒、重度抑郁症和体重指数（BMI））之后，这些关联仍然显着，大多数癌症的风险较高。例如，总体肺癌的调整风险为（OR，1.23；95% CI：1.14-1.33），肺腺癌的调整风险为（OR，1.18；95% CI：1.03-1.36），肺鳞状细胞癌的调整风险为（ OR，1.35；95% CI：1.19-1.53​​），而口腔癌和咽癌则为（OR，1.73；95% CI：1.22-2.44）。尤其值得注意的是，食管癌的风险增加至（OR，2.57；95% CI：1.23-5.37）。中介分析进一步强调 GERD 在 BMI、吸烟、重性抑郁和癌症风险之间的关系中发挥着重要的中介作用。这项研究确定了 GERD 与癌症风险增加之间的显着因果关系，强调了其在癌症发展中的作用，并强调了将 GERD 纳入癌症风险评估的必要性。将 GERD 管理纳入癌症预防策略。© 2024。作者。

Gastroesophageal reflux disease (GERD) is a common condition characterized by the reflux of stomach contents into the esophagus. Despite its widespread prevalence worldwide, the causal link between GERD and various cancer risks has not been fully established, and past medical research has often underestimated or overlooked this relationship.This study performed Mendelian randomization (MR) to investigate the causal relationship between GERD and 19 different cancers. We leveraged data from 129,080 GERD patients and 473,524 controls, along with cancer-related data, obtained from the UK Biobank and various Genome-Wide Association Studies (GWAS) consortia. Single nucleotide polymorphisms (SNPs) associated with GERD were used as instrumental variables, utilizing methods such as inverse variance weighting, weighted median, and MR-Egger to address potential pleiotropy and confounding factors.GERD was significantly associated with higher risks of nine types of cancer. Even after adjusting for all known risk factors-including smoking, alcohol consumption, major depression, and body mass index (BMI)-these associations remained significant, with higher risks for most cancers. For example, the adjusted risk for overall lung cancer was (OR, 1.23; 95% CI: 1.14-1.33), for lung adenocarcinoma was (OR, 1.18; 95% CI: 1.03-1.36), for lung squamous cell carcinoma was (OR, 1.35; 95% CI: 1.19-1.53), and for oral cavity and pharyngeal cancer was (OR, 1.73; 95% CI: 1.22-2.44). Especially noteworthy, the risk for esophageal cancer increased to (OR, 2.57; 95% CI: 1.23-5.37). Mediation analyses further highlighted GERD as a significant mediator in the relationships between BMI, smoking, major depression, and cancer risks.This study identifies a significant causal relationship between GERD and increased cancer risk, highlighting its role in cancer development and underscoring the necessity of incorporating GERD management into cancer prevention strategies.© 2024. The Author(s).