Department of Pharmacology, School of Medicine, University of Athens, Athens, Greece; Hellenic Centre for Disease Control and Prevention, Athens, Greece; Department of Computer Science and Biomedical Informatics, University of Central Greece, Lamia, Greece.
Br J Clin Pharmacol. 2013 Sep;76(3):329-37. doi: 10.1111/bcp.12135.
A growing body of evidence suggests that bisphosphonates may have chemopreventive potential against colorectal cancer. Our aim was to examine this association through a meta-analysis of observational studies.
A comprehensive search for relevant articles published up to October 2012 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random effects and the fixed effects models. Subgroup and sensitivity analyses were also performed.
Eight large population-based epidemiological studies (one case-control, two nested case-control analyses within a cohort and five cohort studies), involving more than 630 000 participants, contributed to the analysis. We found no evidence of publication bias. However, significant heterogeneity was detected among the cohort studies. The analysis revealed a significant protective association between bisphosphonate use and colorectal cancer risk (fixed RR = 0.85, 95% CI 0.80, 0.90, random RR = 0.85, 95% CI 0.75, 0.96). When the analysis was stratified into subgroups according to study design, the association was inverse in both case-control and cohort studies, but only in the former was it statistically significant. The sensitivity analysis confirmed the stability of our results. Furthermore, we found evidence for a dose effect; Long term bisphosphonate use was associated with a 27% decrease in the risk of developing colorectal cancer as compared with non-use (RR = 0.73, 95% CI 0.57, 0.93).
Our findings support a protective effect of bisphosphonates against colorectal cancer. However, further evidence is warranted.
越来越多的证据表明，双膦酸盐类药物可能具有预防结直肠癌的化学预防作用。我们的目的是通过对观察性研究的荟萃分析来检验这种关联。
对截至 2012 年 10 月发表的相关文章进行了全面检索，对每篇研究进行了综述，并提取了数据。在进行荟萃分析之前，评估了研究的发表偏倚和异质性。使用随机效应和固定效应模型计算了合并的相对风险（RR）估计值和 95%置信区间（CI）。还进行了亚组和敏感性分析。
共有 8 项大型基于人群的流行病学研究（1 项病例对照研究，2 项队列内嵌套病例对照分析和 5 项队列研究），涉及超过 630000 名参与者，对分析做出了贡献。我们没有发现发表偏倚的证据。然而，队列研究之间存在显著的异质性。分析显示，双膦酸盐类药物的使用与结直肠癌风险之间存在显著的保护关联（固定 RR=0.85，95%CI 0.80，0.90，随机 RR=0.85，95%CI 0.75，0.96）。当根据研究设计对分析进行分层时，病例对照研究和队列研究都呈负相关，但只有前者具有统计学意义。敏感性分析证实了我们的结果是稳定的。此外，我们发现了剂量效应的证据；与不使用相比，长期使用双膦酸盐类药物与结直肠癌风险降低 27%相关（RR=0.73，95%CI 0.57，0.93）。
我们的研究结果支持双膦酸盐类药物对结直肠癌具有保护作用。然而，还需要进一步的证据。
