Corley Douglas A, Levin Theodore R, Habel Laurel A, Buffler Patricia A
Northern California Kaiser Permanente Division of Research, Oakland 94612, USA.
Am J Gastroenterol. 2006 May;101(5):937-44. doi: 10.1111/j.1572-0241.2006.00539.x.
Medications that may increase gastroesophageal reflux could be risk factors for esophageal adenocarcinoma; however, epidemiologic studies present conflicting results. We evaluated patients with a high-risk condition, Barrett's esophagus, to identify risk factors that may act early in the carcinogenic process.
We conducted a nested case-control study within a large integrated health-services organization. Electronic databases were used to identify incident diagnoses of Barrett's esophagus (cases); two controls were matched to each case. Electronic databases provided information on the use of medications that may induce reflux (nitrates, calcium channel blockers, xanthines, benzodiazepines, and beta agonists) and potential confounders. A supplemental mailed questionnaire evaluated additional potential confounders.
We identified 421 cases and selected 842 controls. The association between any medication use and a Barrett's esophagus diagnosis was modified by age; an increased risk was observed only among subjects <70 yr of age (adjusted odds ratio [OR] = 2.6; 95% confidence interval [CI] 1.5-4.6). A Barrett's esophagus diagnosis was associated with asthma medication use (OR 5.8; 95% CI 2.2, 14.9), but not with the other medications studied. Subgroup analyses suggested that medication use was not independently associated with reflux symptoms and that adjustment for asthma symptoms substantially reduced the association between medication use and a Barrett's esophagus diagnosis.
The use of medications that may induce reflux was associated with a Barrett's esophagus diagnosis among younger persons. This association was only observed with asthma medications; the analyses suggested the possibility of confounding by indication, whereby reflux may cause both asthma and Barrett's esophagus.
可能增加胃食管反流的药物可能是食管腺癌的危险因素;然而,流行病学研究结果相互矛盾。我们评估了患有高危疾病巴雷特食管的患者,以确定可能在致癌过程早期起作用的危险因素。
我们在一个大型综合医疗服务机构内进行了一项巢式病例对照研究。使用电子数据库识别巴雷特食管的新发诊断病例(病例组);每个病例匹配两名对照。电子数据库提供了有关可能诱发反流的药物(硝酸盐、钙通道阻滞剂、黄嘌呤、苯二氮䓬类药物和β受体激动剂)的使用情况以及潜在混杂因素的信息。一份补充邮寄问卷评估了其他潜在混杂因素。
我们识别出421例病例并选择了842名对照。任何药物使用与巴雷特食管诊断之间的关联因年龄而异;仅在年龄<70岁的受试者中观察到风险增加(校正比值比[OR]=2.6;95%置信区间[CI]1.5 - 4.6)。巴雷特食管诊断与哮喘药物使用相关(OR 5.8;95%CI 2.2,14.9),但与其他研究药物无关。亚组分析表明,药物使用与反流症状并非独立相关,并且对哮喘症状进行校正后,药物使用与巴雷特食管诊断之间的关联大幅降低。
可能诱发反流的药物使用与较年轻人群的巴雷特食管诊断相关。仅在哮喘药物使用中观察到这种关联;分析提示可能存在指征性混杂,即反流可能同时导致哮喘和巴雷特食管。