Xue Fei, Xue Jiajing, Zhao Bingbing, Zhu Shuai
Department of General Surgery, Yan'an People's Hospital, Yan'an, China; 2Graduate Division, Xi'an Medical University, Xi'an, China.
Gut Liver. 2025 Apr 11. doi: 10.5009/gnl240440.
BACKGROUND/AIMS: Gastrointestinal diseases present a significant global health challenge and greatly impact healthcare expenditures. Despite alcohol, tobacco, and coffee being universally recognized risk factors for various gastrointestinal disorders, the exact causal linkages have not been clarified because of the predominance of observational studies on this topic. Mendelian randomization (MR) was used to explore to what extent alcohol, tobacco, and coffee increase the risk of developing 13 upper and lower gastrointestinal diseases.
Genetic data from large genome-wide association studies including GSCAN, FinnGen, UK Biobank, IIBDGC, GERA, and other consortia were used for both univariable and multivariable MR analyses. Single-nucleotide polymorphisms were used as instrumental variables and sensitivity analyses were conducted to identify potential pleiotropic effects.
Genetically predicted smoking was positively associated with esophageal cancer, Crohn's disease, gastric ulcer, irritable bowel syndrome, and gastroesophageal reflux risk, but was negatively associated with celiac disease risk. Alcohol intake was positively correlated with both esophageal cancer and chronic gastritis risk. These findings were confirmed by multivariable MR analyses, albeit with some variations. Coffee consumption was linked to esophageal cancer, but the association became nonsignificant after adjusting for hot beverage consumption.
This comprehensive MR study suggests that alcohol and tobacco consumption are associated with the occurrence of several gastrointestinal diseases. These results support the need for public health initiatives to reduce smoking and alcohol abuse, with the aim of preventing both upper and lower gastrointestinal diseases.
背景/目的：胃肠道疾病是一项重大的全球健康挑战，对医疗保健支出有很大影响。尽管酒精、烟草和咖啡被公认为是各种胃肠道疾病的危险因素，但由于关于该主题的观察性研究占主导地位，确切的因果关系尚未明确。采用孟德尔随机化（MR）方法来探究酒精、烟草和咖啡在多大程度上会增加患13种上、下胃肠道疾病的风险。
来自大型全基因组关联研究（包括GSCAN、芬兰基因库、英国生物银行、炎症性肠病基因组学联盟、遗传与环境因素对成人健康影响研究及其他合作项目）的基因数据用于单变量和多变量MR分析。单核苷酸多态性用作工具变量，并进行敏感性分析以识别潜在的多效性效应。
基因预测的吸烟与食管癌、克罗恩病、胃溃疡、肠易激综合征和胃食管反流风险呈正相关，但与乳糜泻风险呈负相关。酒精摄入与食管癌和慢性胃炎风险均呈正相关。这些发现通过多变量MR分析得到证实，尽管存在一些差异。咖啡消费与食管癌有关，但在调整热饮消费后，这种关联变得不显著。
这项全面的MR研究表明，饮酒和吸烟与几种胃肠道疾病的发生有关。这些结果支持开展公共卫生行动以减少吸烟和酗酒的必要性，旨在预防上、下胃肠道疾病。
