WITHDRAWN: Oral bisphosphonates for the risk and survival of colorectal cancer: a quantitative synthesis of observational studies

Abstract

Several preclinical studies have suggested that bisphosphonates (BPs) may have anti-neoplastic effects against colorectal cancer (CRC). However, the magnitude of this association has not been fully determined. The aim of this study was to synthesize the existing evidence on the association between BP intake and risk or mortality of CRC. Three relevant databases including Pubmed, Embase and Cochrane Library were searched from initial to August 2017. Combined relative risks (RRs)or hazard ratios (HRs) with 95% confidence interval (95% CI) were pooled using a random-effects model. Thirteen studies enrolling 3,464,335 individuals were eligible for inclusion, with 11 studies investigating associations between BP use and CRC risk and 3 studies examining BP use and CRC mortality. Comparing with non-BP users, the summary RRs for CRC risk in BP users were 0.87 (95% CI, 0.79 to 0.97). Subgroup analyses revealed that this association was robust for nested case-control studies and especially evident for rectal cancer. We did not find survival benefits of BP use for CRC patients in terms of overall survival (HR 0.74, 95% CI 0.43 to 1.27) or cancer-specific survival (HR 0.71, 95% CI 0.44 to 1.15). Our findings suggest that oral BP use may be associated with reduced risk of CRC, while further larger cohort studies should be advocated to determine the true relationship between BP use and CRC mortality in specific patients.