Lagergren J, Bergström R, Adami H O, Nyrén O
Karolinska Institutet and Danderyd Hospital, Stockholm, Sweden.
Ann Intern Med. 2000 Aug 1;133(3):165-75. doi: 10.7326/0003-4819-133-3-200008010-00007.
The incidence of esophageal adenocarcinoma is increasing rapidly. Gastroesophageal reflux is a strong risk factor for this disease. The increase in incidence of esophageal adenocarcinoma coincided with the introduction of medications that promote reflux by relaxing the lower esophageal sphincter (LES), such as nitroglycerin, anticholinergics, beta-adrenergic agonists, aminophyllines, and benzodiazepines.
To test the possible association between use of LES-relaxing medications and risk for adenocarcinoma of the esophagus and gastric cardia.
A nationwide population-based case-control study with in-person interviews.
Sweden, 1995 through 1997.
189 patients with newly diagnosed esophageal adenocarcinoma, 262 with adenocarcinoma of the gastric cardia, and 167 with esophageal squamous-cell carcinoma were compared with 820 population-based controls.
Estimated incidence rate ratios, calculated by using multivariate logistic regression from case-control data with adjustment for potential confounding.
Past use of LES-relaxing drugs was positively associated with risk for esophageal adenocarcinoma. Among daily, long-term users (>5 years) of LES-relaxing drugs, the estimated incidence rate ratio was 3.8 (95% CI, 2.2 to 6.4) compared with persons who had never used these drugs. Drugs of all classes contributed to the increased risk, but the association was particularly strong for anticholinergics. Short-term use of other types of LES-relaxing drugs did not seem to be strongly associated with risk. The association almost disappeared after adjustment for reflux symptoms, indicating that promotion of reflux is the link between use of LES-relaxing drugs and esophageal adenocarcinoma. If 15,490 men in any age group take LES-relaxing drugs daily for 5 years, 1 additional case of adenocarcinoma would be expected (number needed to treat for harm); in men older than 60 years of age, the number needed to treat for harm is 5,570. Assuming a causal relation, about 10% of the esophageal adenocarcinomas occurring in the population may be attributable to intake of LES-relaxing drugs. Cardia adenocarcinoma and esophageal squamous-cell carcinoma were not associated with use of LES-relaxing drugs.
The widespread use of LES-relaxing drugs may have contributed to the increasing incidence of esophageal adenocarcinoma.
食管腺癌的发病率正在迅速上升。胃食管反流是该疾病的一个重要危险因素。食管腺癌发病率的增加与一些通过松弛食管下括约肌（LES）促进反流的药物的使用有关，如硝酸甘油、抗胆碱能药物、β-肾上腺素能激动剂、氨茶碱和苯二氮䓬类药物。
检测使用LES松弛药物与食管和贲门腺癌风险之间的可能关联。
一项基于全国人口的病例对照研究，并进行面对面访谈。
瑞典，1995年至1997年。
189例新诊断的食管腺癌患者、262例贲门腺癌患者和167例食管鳞状细胞癌患者与820名基于人群的对照者进行比较。
通过多因素逻辑回归对病例对照数据进行分析，并对潜在混杂因素进行调整后计算估计发病率比。
既往使用LES松弛药物与食管腺癌风险呈正相关。在每日长期（>5年）使用LES松弛药物的人群中，与从未使用过这些药物者相比，估计发病率比为3.8（95%CI，2.2至6.4）。所有类型的药物均导致风险增加，但抗胆碱能药物的关联尤为强烈。短期使用其他类型的LES松弛药物似乎与风险无强烈关联。在调整反流症状后，这种关联几乎消失，表明促进反流是使用LES松弛药物与食管腺癌之间的联系。如果任何年龄组的15490名男性每日服用LES松弛药物5年，预计会额外出现1例腺癌病例（危害所需治疗人数）；在60岁以上的男性中，危害所需治疗人数为5570。假设存在因果关系，人群中约10%的食管腺癌可能归因于LES松弛药物的摄入。贲门腺癌和食管鳞状细胞癌与使用LES松弛药物无关。
LES松弛药物的广泛使用可能导致了食管腺癌发病率的上升。
