Thiazolidinediones and risk of colorectal cancer in patients with diabetes mellitus: A meta-analysis.

Background/Aims: A growing body of evidence has suggested that thiazolidinediones (TZDs) potentially reduce the risk of colorectal cancer (CRC). This study aimed to evaluate the effect of TZDs on CRC risk in patients with diabetes mellitus (DM). Patients and Methods: A systematic search of electronic databases was performed for studies evaluating the exposure to TZDs and reporting CRC risk in diabetic patients. Pooled estimates with 95% confidence intervals (CIs) were estimated using fixed or random effects models. Results: A total of 10 observational studies reporting more than 18,972 CRC cases in 2,470,768 DM patients were included. Meta-analysis showed a 9% reduction in CRC risk associated with TZDs use in all studies [relative risk (RR) =0.91, 95% CI = 0.84-0.99, P = 0.03] and cohort studies (RR = 0.89, 95% CI = 0.80-0.99, P = 0.04), respectively. However, such effect was not shown in case-control studies. In subgroup analyses, lower CRC risk was found in Asian population (RR = 0.40, 95% CI = 0.29-0.53, P = 0.00), and a trend toward lower CRC risk was observed in US population (RR = 0.94, 95% CI = 0.88-1.01, P = 0.08). CRC risk was significantly modified with non-pioglitazone TZD use (RR = 0.88, 95% CI = 0.82-0.95, P = 0.00), but not with pioglitazone use (RR = 0.95, 95% CI = 0.89-1.01, P = 0.11). No significant difference was observed with cancer site (colon or rectum). There was considerable inherent heterogeneity across studies, partly explained by study location. Conclusions: This meta-analysis supports a protective association between TZDs use and CRC risk in patients with DM. Future well-designed prospective studies with larger cohorts would be needed to understand this association better.