Insulin, Glucose, Insulin Resistance and Incident Colorectal Cancer in Male Smokers

Background & Aims—Hyperinsulinemia is a putative colorectal cancer (CRC) risk factor. Insulin resistance (IR) commonly precedes hyperinsulinemia and can be quantitatively measured using the homeostasis model assessment-insulin resistance (HOMA-IR) index. To date, few studies have directly examined serum insulin as an indicator of CRC risk and none have reported associations based on HOMA-IR. Methods—We performed a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (n=29,133). Baseline exposure and fasting serum biomarker data were available for 134 incident CRC case and 399 non-case subjects. HOMA-IR was derived as fasting insulin x fasting glucose/22.5. Hazard ratios and 95 % confidence intervals (HR; 95 % CIs) were estimated using age-adjusted and multivariable-adjusted Cox proportional hazards regression models. Results—Median (IQR) values for serum insulin, glucose and HOMA-IR were 4.1 (2.9–7.2) mIU/ L, 101 (94–108) mg/dL, and 0.99 (0.69–1.98) for case subjects and 4.1 (2.7–6.1) mIU/L, 99 (93– 107) mg/dL, and 1.02 (0.69–1.53) for non-case subjects, respectively. Based on comparison of th