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

https://doi.org/10.1016/j.cgh.2006.09.014Get rights and content

Background & Aims: Hyperinsulinemia is a putative colorectal cancer (CRC) risk factor. Insulin resistance (IR) commonly precedes hyperinsulinemia and can be quantitatively measured by 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 on the basis of 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 × fasting glucose/22.5. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by using age-adjusted and multivariable-adjusted Cox proportional hazards regression models. Results: Median (interquartile range) 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. On the basis of comparison of the highest versus lowest quartiles for each biomarker, insulin (HR, 1.84; 95% CI, 1.03–3.30) and HOMA-IR (HR, 1.85; 95% CI, 1.06–3.24) were significantly associated with incident CRC, whereas glucose was marginally associated with incident CRC (HR, 1.70; 95% CI, 0.92–3.13) in age-adjusted risk models. However, trends across biomarker quartiles were somewhat inconsistent (P trend = .12, .04, and .12, respectively), and multivariable adjustment generally attenuated the observed risk estimates. Conclusions: Data from this prospective study of male smokers provide limited support for hyperinsulinemia, hyperglycemia, and/or insulin resistance as CRC risk factors.

Section snippets

Materials and Methods

Details regarding design and conduct of the ATBC Study have been previously described.27 In brief, 29,133 men ages 50–69 years who lived in southwestern Finland and smoked at least 5 cigarettes per day were recruited between 1985–1988. Individuals with a previous cancer history (except non-melanoma skin cancer) were excluded. Enrolled trial participants provided a fasting blood sample before randomization, from which serum specimens were isolated, aliquoted, and stored deep-frozen at −70°C for

Results

Selected baseline characteristics of the CRC case and subcohort non-case subjects are shown in Table 1. CRC case subjects were slightly older (P < .001) and less physically active at work (P = .006) than the non-case subjects. Median (interquartile range) 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.

Discussion

In this prospective study of Finnish male smokers, baseline fasting insulin and HOMA-IR were positively associated with incident CRC in age-adjusted risk models. Glucose was also associated with increased CRC risk, but the age-adjusted risk estimate did not achieve statistical significance. These data add to the limited number of published reports wherein circulating insulin and/or glucose concentrations have been directly examined in relation to incident CRC. We also provide novel data

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    Supported by US Public Health Service contracts N01-CN-45165, N01-RC-45035, and N01-RC-37004; Intramural Research Program and the Division of Cancer Epidemiology and Genetics; National Cancer Institute, National Institutes of Health, Department of Health and Human Services; and supported by National Cancer Institute Grant K07 CA-92216 (P.J.L.).

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    Copyright © 2006 AGA Institute. Published by Elsevier Ltd. All rights reserved.