Benign prostatic hyperplasia is a significant risk factor for bladder cancer in diabetic patients: a population-based cohort study using the National Health Insurance in Taiwan

Abstract

BackgroundDiabetic patients have a higher risk of bladder cancer and benign prostatic hyperplasia (BPH). Theoretically, BPH patients may have an increased risk of bladder cancer because residual urine in the bladder surely increases the contact time between urinary excreted carcinogens and the urothelium. However, whether BPH increases bladder cancer risk in patients with type 2 diabetes has not been studied.MethodsThe reimbursement databases of all Taiwanese diabetic patients under oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006 and a total of 547584 men with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Incidences of bladder cancer for BPH by status and by duration were calculated and adjusted hazard ratios (95% confidence intervals) were estimated by Cox regression. The effects of diabetes duration and medications used for diabetic control in relation with bladder cancer risk were also evaluated by Cox regression in BPH men.ResultsThe incidences were 258.77 and 69.34 per 100,000 person-years for patients with and without BPH, respectively, adjusted hazard ratio 1.794 (1.572, 2.047). For BPH patients, those who underwent surgical procedures for BPH had a higher incidence than those who did not (355.45 vs. 250.09 per 100,000 person-years), respective adjusted hazard ratios: 2.459 (1.946, 3.109) and 1.709 (1.492, 1.958). The significantly higher risk could be demonstrated for BPH of any duration: respective adjusted hazard ratios 1.750 (1.430, 1.605), 1.844 (1.543, 2.203), 2.011 (1.680, 2.406) and 1.605 (1.341, 1.921) for BPH <1, 1–3, 3–5 and ≥5 years versus patients without BPH. Sensitivity analyses for patients aged ≥60 years and after excluding BPH patients with surgical procedures or without surgical procedures, respectively, yielded similar results. In BPH men, diabetes duration was not significantly related with bladder cancer; but metformin was consistently associated with a significantly lower risk, with adjusted hazard ratio of 0.719 (0.590, 0.875) for all ages and 0.742 (0.604, 0.912) for age ≥60 years.ConclusionsBPH is a significant risk factor for bladder cancer in men with type 2 diabetes. Metformin may protect against bladder cancer in BPH men.

A Review on Thiazolidinediones and Bladder Cancer in Human Studies

“…The adjusted hazard ratio (95% CI) for bladder cancer for ever-users versus never-users of rosiglitazone was 1.124 (0.923-1.369) [51]. The hazard ratio for pioglitazone and the limitations of the study have been discussed previously.…”

“…A recent study from Taiwan does not support an impact of insulin on the risk of bladder cancer incidence in patients with type 2 diabetes [51]. However, in another 12-year follow-up study of a national cohort of 86,939 patients with type 2 diabetes in Taiwan, insulin users had significantly higher risk of Downloaded by [Korea University] at 17:47 27 December 2014 bladder cancer mortality than nonusers with hazard ratios ranging from 1.877 to 2.502 in different analyses [102].…”

“…The major population-based cohorts used in these studies are derived from administrative databases, which include the Kaiser Permanente Northern California (KPNC) database in the United States [9,45], the US pharmacy claims database [46], the national health insurance in France (the CNAMTs study: Caisse Nationale d'Assurance Maladie des Travailleurs Salariés) [11], the Health Improvement Network (THIN) or General Practice Research Database (GPRD) in UK [47][48][49], and the National Health Insurance (NHI) reimbursement databases of Taiwan [50][51][52][53][54][55][56]. Hospital-based design was applied in a Japanese report [57] and in a Korean study [58].…”

“…Prostatic Hyperplasia) In a second study drawn from the entire national database, the association between benign prostatic hyperplasia and bladder cancer risk was evaluated in patients with type 2 diabetes, which showed an adjusted hazard ratio (95% CI) of 1.794 (1.572-2.047) for a diagnosis of benign prostatic hyperplasia [51]. In a subgroup analysis of 85,152 men with type 2 diabetes and having benign prostatic hyperplasia, the adjusted hazard ratios (95% CI) for bladder cancer in ever-users of pioglitazone and rosiglitazone were 1.023 (0.752-1.393) and 1.124 (0.923-1.369), respectively, while compared to never-users of the respective drugs.…”

“…For example, the UK GPRD was used in the studies by Mamtani and colleagues [47], Wei and associates [48] and Azoulay and coauthors [49]. On the other hand, Tseng [50][51][52][53], Chang and colleagues [54], Hsiao and associates [55] and Kao and coauthors [56] the Taiwanese NHI database for their studies. Some of the investigators used a retrospective cohort study design and some used a case-control design from the same databases (Table 2).…”