Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Clin Gastroenterol Hepatol. 2013 Mar;11(3):232-9.e1. doi: 10.1016/j.cgh.2012.11.026. Epub 2012 Dec 4.
BACKGROUND & AIMS: Colorectal cancer (CRC) is the third most common cancer worldwide. Several preclinical and observational studies have shown that bisphosphonates may have chemopreventive effects against CRC. We performed a systematic review and meta-analysis of all studies evaluating the effect of bisphosphonates on the risk of CRC.
We conducted a systematic search of Medline, Embase, and Web of Science through August 2012 and manually reviewed the literature. Studies were included if they met the following criteria: (1) evaluated and clearly defined exposure to bisphosphonates, (2) reported CRC outcomes, and (3) reported relative risks or odds ratio (OR) or provided sufficient data for their estimation. Summary OR estimates with 95% confidence intervals (CIs) were estimated using the random-effects model. Statistical heterogeneity was assessed with the Cochran's Q and I(2) statistic.
We analyzed data from 6 population-based observational studies reporting 20,001 cases of CRC in 392,106 patients. A meta-analysis of these studies showed a statistically significant 17% reduction in CRC incidence with bisphosphonate use (unadjusted OR, 0.83; 95% CI, 0.76-0.90), with borderline heterogeneity across studies (Cochran's Q, P = .16; I(2) = 37%). This effect persisted after correcting for multiple covariates in individual studies (adjusted OR, 0.85; 95% CI, 0.74-0.98). When the analysis was restricted to women only, use of bisphosphonates was associated with a 16% reduction in CRC incidence, which bordered on statistical significance (n = 5 studies; adjusted OR, 0.84; 95% CI, 0.70-1.01). This chemopreventive effect of bisphosphonates was observed for proximal and distal colon cancers, as well as rectal cancer, independently.
Based on meta-analysis, bisphosphonate use is associated with a modest, but statistically significant, reduction in CRC risk.
结直肠癌（CRC）是全世界第三大常见癌症。一些临床前和观察性研究表明，双膦酸盐可能对 CRC 具有化学预防作用。我们对所有评估双膦酸盐对 CRC 风险影响的研究进行了系统评价和荟萃分析。
我们通过 2012 年 8 月对 Medline、Embase 和 Web of Science 进行了系统搜索，并手动审查了文献。如果研究符合以下标准，则将其纳入：（1）评估并明确界定双膦酸盐暴露，（2）报告 CRC 结果，以及（3）报告相对风险或比值比（OR）或提供足够的数据进行估计。使用随机效应模型估计具有 95%置信区间（CI）的汇总 OR 估计值。使用 Cochran's Q 和 I(2)统计量评估统计异质性。
我们分析了来自 6 项基于人群的观察性研究的数据，这些研究共纳入了 392,106 例患者中的 20,001 例 CRC 病例。对这些研究的荟萃分析显示，使用双膦酸盐可使 CRC 发病率降低 17%（未调整的 OR，0.83；95%CI，0.76-0.90），但研究间存在边缘异质性（Cochran's Q，P =.16；I(2) = 37%）。在对个体研究中的多个协变量进行校正后，这种效果仍然存在（校正后的 OR，0.85；95%CI，0.74-0.98）。当分析仅限于女性时，使用双膦酸盐与 CRC 发病率降低 16%相关，这一结果接近统计学意义（n = 5 项研究；校正后的 OR，0.84；95%CI，0.70-1.01）。这种双膦酸盐的化学预防作用独立地观察到近端和远端结肠癌以及直肠癌。
基于荟萃分析，双膦酸盐的使用与 CRC 风险适度但具有统计学意义的降低相关。
