Chow W H, Finkle W D, McLaughlin J K, Frankl H, Ziel H K, Fraumeni J F
Division of Cancer Etiology, National Cancer Institute, Bethesda, Md, USA.
JAMA. 1995 Aug 9;274(6):474-7.
To examine the relationship of gastrointestinal disorders and their treatment to the risk of adenocarcinomas of the esophagus and gastric cardia (AEC).
A medical record-based case-control study, with data collected on a standardized form by a trained abstractor, blind to the case-control status.
A large prepaid health plan.
Case patients were plan members newly diagnosed with histologically confirmed AEC from 1986 to 1992. For each of the 196 eligible case patients, one control was selected who matched for membership at time of diagnosis, sex, year of birth, and duration of membership.
Association between AEC and history of gastroesophageal conditions and their treatment. Conditional logistic regression procedures were used for calculation of odds ratios (ORs) and corresponding 95% confidence intervals (Cls), with adjustment for race, smoking status, and body mass index. Medications were grouped into H2 antagonists (cimetidine, ranitidine, famotidine, and nizatidine) and anticholinergics (propantheline bromide, dicyclomine hydrochloride, Donnatal [combination of atropine sulfate, hyoscyamine sulfate, phenobarbital, and scopolamine hydrobromide], and Librax [combination of chlordiazepoxide hydrochloride and clidinium bromide]).
Significant twofold or greater risks of AEC were associated with a history of esophageal reflux, hiatal hernia, esophagitis/esophageal ulcer, and difficulty swallowing. The ORs increased with increasing number of these conditions. Although a fourfold risk was linked to four or more prescriptions for H2 antagonists, the risk was reduced to 1.5 (95% Cl, 0.4 to 5.4) after adjusting for the predisposing conditions. Further analysis revealed that the excess risk was restricted to persons with a history of gastroesophageal reflux and related conditions. No association was observed for overall use of anticholinergics. However, after adjustment for predisposing conditions, ORs decreased with increasing number of prescriptions for anticholinergics (P for trend = .08)
This study provides reassuring findings that use of H2 antagonists and anticholinergics does not increase AEC risk. It also quantifies the elevated risk of AEC associated with gastroesophageal reflux disease. Further research into reflux disease and the production of premalignant epithelial changes may help elucidate carcinogenic mechanisms and measures aimed at early detection and prevention of AEC.
研究胃肠道疾病及其治疗与食管和贲门腺癌（AEC）风险之间的关系。
一项基于病历的病例对照研究，由经过培训的提取人员使用标准化表格收集数据，提取人员对病例对照状态不知情。
一个大型的预付健康计划。
病例组患者为1986年至1992年新诊断为经组织学确诊的AEC的计划成员。对于196名符合条件的病例患者中的每一位，选择一名在诊断时的会员资格、性别、出生年份和会员期限相匹配的对照。
AEC与胃食管疾病病史及其治疗之间的关联。采用条件逻辑回归程序计算比值比（OR）和相应的95%置信区间（Cl），并对种族、吸烟状况和体重指数进行调整。药物分为H2拮抗剂（西咪替丁、雷尼替丁、法莫替丁和尼扎替丁）和抗胆碱能药物（溴丙胺太林、盐酸双环维林、唐那泰[硫酸阿托品、硫酸氢溴酸东莨菪碱、苯巴比妥和氢溴酸东莨菪碱的组合]和利眠宁[盐酸氯氮卓和溴化氯地昔宁的组合]）。
食管反流、食管裂孔疝、食管炎/食管溃疡和吞咽困难病史与AEC风险显著增加两倍或更多相关。这些疾病的数量增加，OR也增加。虽然四倍的风险与H2拮抗剂的四张或更多处方有关，但在对易感疾病进行调整后，风险降至1.5（95%Cl，0.4至5.4）。进一步分析表明，额外风险仅限于有胃食管反流和相关疾病病史的人。未观察到抗胆碱能药物总体使用与AEC之间的关联。然而，在对易感疾病进行调整后，OR随着抗胆碱能药物处方数量的增加而降低（趋势P = 0.08）。
本研究提供了令人安心的结果，即使用H2拮抗剂和抗胆碱能药物不会增加AEC风险。它还量化了与胃食管反流病相关的AEC风险升高。对反流病和癌前上皮变化产生的进一步研究可能有助于阐明致癌机制以及旨在早期检测和预防AEC的措施。
