Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands.
Int J Cancer. 2017 Jul 1;141(1):62-71. doi: 10.1002/ijc.30717.
Recent experimental and epidemiological studies have suggested that beta-blocker use might be associated with better cancer prognosis, but results were inconclusive and only few studies have investigated the association specifically for colorectal cancer (CRC) patients. We investigated this hypothesis using a linked dataset of the Eindhoven area of the Netherlands Cancer Registry and the PHARMO record linkage, including patients diagnosed with CRC between 1998 and 2011. Eligible patients were matched on propensity scores to control for potential confounders such as socio-demographic factors, comorbidity, cancer treatment and use of other medications. Controls were subsequently restricted to active comparators. The association between pre-diagnostic and time-dependent post-diagnostic beta-blocker use and overall survival was estimated using Cox proportional hazard regression models. Subgroup analyses by cancer site and stage and by beta-blocker type were conducted. Of 8,100 CRC patients with a median follow-up of 6.6 years, 1,813 (22%) used beta-blockers prior to diagnosis. In multivariate analysis, we observed no significant association in overall mortality for pre-diagnostic [hazard ratio 1.07, 95% confidence interval (0.96-1.19)] and post-diagnostic [1.10 (0.98-1.23)] beta-blocker use, respectively. Analyses by beta-blocker type, by cancer site, cancer stage and by cumulative dose showed no significant survival improvements for beta-blocker users. However, there was a significant association between cumulative duration of use of 1-12 months and increased overall mortality [1.20 (1.03-1.39)]. Thus, our results do not support the hypothesis of a beneficial effect of pre- or post-diagnostic beta-blocker intake on CRC prognosis, neither for specific patient subgroups nor for specific types of beta-blockers.
最近的实验和流行病学研究表明,β受体阻滞剂的使用可能与更好的癌症预后相关,但结果尚无定论,只有少数研究专门调查了β受体阻滞剂与结直肠癌(CRC)患者的相关性。我们使用荷兰癌症登记处埃因霍温地区的一个关联数据集和 PHARMO 记录链接来研究这一假设,该数据集包括 1998 年至 2011 年间诊断为 CRC 的患者。合格的患者通过倾向评分进行匹配,以控制潜在的混杂因素,如社会人口因素、合并症、癌症治疗和其他药物的使用。随后,将对照限制为活性对照。使用 Cox 比例风险回归模型估计诊断前和时间依赖性诊断后β受体阻滞剂使用与总生存之间的关联。进行了按癌症部位和阶段以及β受体阻滞剂类型的亚组分析。在中位随访 6.6 年的 8100 例 CRC 患者中,有 1813 例(22%)在诊断前使用了β受体阻滞剂。在多变量分析中,我们观察到诊断前[风险比 1.07,95%置信区间(0.96-1.19)]和诊断后[1.10(0.98-1.23)]β受体阻滞剂使用与总体死亡率均无显著关联。按β受体阻滞剂类型、癌症部位、癌症阶段和累积剂量进行的分析表明,β受体阻滞剂使用者的生存无显著改善。然而,使用 1-12 个月的累积时间与总死亡率增加之间存在显著关联[1.20(1.03-1.39)]。因此,我们的结果不支持诊断前或诊断后β受体阻滞剂摄入对 CRC 预后有益的假设,无论是对于特定的患者亚组还是对于特定类型的β受体阻滞剂。