Xie Shao-Hua, Jernberg Tomas, Mattsson Fredrik, Lagergren Jesper
Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden.
Oncotarget. 2017 May 23;8(21):34727-34735. doi: 10.18632/oncotarget.16151.
Gastrointestinal cancers are characterized by a male predominance, suggesting a role of sex hormones. We hypothesized that digitalis medication, due to its estrogenic properties, decreases the risk of male-predominated gastrointestinal cancers.
Long -term digitalis use (≥2 years) was followed by decreased risk for several gastrointestinal cancers, but associations were statistically significant only for liver cancer (hazard ratio [HR]=0.40, 95% confidence interval (CI) 0.16-0.98). Short-term (<1 year) use was associated with an increased risk of esophageal squamous cell carcinoma (HR=1.79, 95% CI 1.01-3.17), colorectal cancer (HR=1.72, 95% CI 1.57-1.89), gallbladder cancer (HR=1.93, 95% CI 1.04-3.59), and pancreatic cancer (HR=1.33, 95% CI 1.00-1.76), but no such increase was found among long-term users.
We performed a nationwide population-based cohort study in Sweden. Participants included 156,385 individuals using digitalis and a reference group of 551,933 users of organic nitrates between 2005 and 2013, who were identified in the Swedish Prescribed Drug Register. New diagnoses of gastrointestinal cancers were identified from the Swedish Cancer Register. Hazard ratios of gastrointestinal cancers in digitalis users compared to users of organic nitrates were calculated from Cox proportional hazards regression with adjustment for sex, age, municipality of residence and comorbidity.
This study suggests a decreased risk of male-predominated gastrointestinal cancers, particularly of liver cancer, in long-term users of digitalis. Short-term use may be associated with an increased risk of esophageal squamous cell carcinoma, colorectal cancer, gallbladder cancer, and pancreatic cancer.The use of digitalis as preventive or therapeutic agents remains to be fully evaluated.
胃肠道癌症的特点是男性居多，这表明性激素发挥了作用。我们推测，洋地黄药物因其雌激素特性，可降低以男性为主的胃肠道癌症的风险。
长期使用洋地黄（≥2年）后，多种胃肠道癌症的风险降低，但仅肝癌的关联具有统计学意义（风险比[HR]=0.40，95%置信区间[CI]0.16 - 0.98）。短期（<1年）使用与食管鳞状细胞癌风险增加相关（HR=1.79，95%CI 1.01 - 3.17）、结直肠癌（HR=1.72，95%CI 1.57 - 1.89）、胆囊癌（HR=1.93，95%CI 1.04 - 3.59）和胰腺癌（HR=1.33，95%CI 1.00 - 1.76），但长期使用者中未发现此类增加。
我们在瑞典进行了一项基于全国人口的队列研究。参与者包括2005年至2013年间使用洋地黄的156,385人以及作为参照组的551,933名使用有机硝酸盐的使用者，他们在瑞典处方药登记册中被识别。胃肠道癌症的新诊断信息来自瑞典癌症登记册。通过Cox比例风险回归计算洋地黄使用者与有机硝酸盐使用者相比胃肠道癌症的风险比，并对性别、年龄、居住市和合并症进行了调整。
本研究表明，长期使用洋地黄的人群中，以男性为主的胃肠道癌症，尤其是肝癌的风险降低。短期使用可能与食管鳞状细胞癌、结直肠癌、胆囊癌和胰腺癌风险增加相关。洋地黄作为预防或治疗药物的用途仍有待全面评估。
