Background: Epidemiological studies have shown that diabetes mellitus (DM) is associated with an increased risk of cancer. The aim of this study was to examine the association of diabetes with subsequent internal cancers in an arsenic-exposed area where the prevalence of diabetes is remarkably higher than in the general Taiwan population. Methods: The southwestern cohort was recruited from blackfoot disease (BFD) endemic townships with high arsenic levels in their well water, while the northeastern cohort was recruited from four townships in the Lanyang Basin with low-to-moderate arsenic level in their well water. These two cohorts were combined and a total of 9525 subjects were recruited for the analysis. The disease status of the subjects, including diabetes, hypertension or dyslipidemia, was ascertained through linkage with the computerized Taiwan National Health Insurance (NHI) database, while the cancer status of the subjects was ascertained through linkage with National Cancer Registry and via the NHI database for major illness/injury certificates/catastrophic illness cards. The subjects were followed from study entry through December 31, 2009. Cox regression analysis with time-dependent DM status was used to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for developing internal malignancies. Results: Diabetic patients had a 58% higher risk of any site internal cancer compared to non-DM individuals (HR, 1.58; 95% CI: 1.39-1.79) after adjusting for age, sex, education level, cigarette smoking, alcohol drinking, geographical location, cumulative arsenic exposure and history of hypertension or dyslipidemia. A significant association of DM with cancers of the stomach (HR, 1.75; 95% CI: 1.12-2.76), colon (HR, 1.76; 95% CI: 1.20-2.59), liver (HR, 2.46; 95% CI: 1.81-3.34), pancreas (HR, 2.80; 95% CI: 1.30-6.20) and lungs (HR, 1.35; 95% CI: 1.04-1.76) was observed. The association with lung, bladder and kidney cancer was largely confined to diabetic patients with arsenic level in consumed water ≧500. μg/L, while the association with other cancer sites did not show such an effect. With the adjustment of arsenic exposure, marked attenuation for the association was observed, suggesting high level arsenic exposure plays an important role in the development of diabetes mellitus and concomitantly lung, bladder and kidney cancer.
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