Insulin, glucose, insulin resistance, and incident colorectal cancer in male smokers.

Abstract

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 x 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.

• Authors: Paul J Limburg, Rachael Z Stolzenberg-Solomon, Robert A Vierkant, Katherine Roberts, Thomas A Sellers, Philip R Taylor, Jarmo Virtamo, James R Cerhan, Demetrius Albanes
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 4 Issue 12 Pg. 1514-21 (Dec 2006) ISSN: 1542-3565 [Print] United States
• PMID: 17162243 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Biomarkers, Tumor
• Blood Glucose
• Insulin

Topics

• Aged
• Biomarkers, Tumor (blood)
• Blood Glucose (metabolism)
• Colorectal Neoplasms (blood, epidemiology, etiology)
• Finland (epidemiology)
• Follow-Up Studies
• Humans
• Hyperinsulinism (blood, complications, epidemiology)
• Incidence
• Insulin (blood)
• Insulin Resistance (physiology)
• Male
• Middle Aged
• Prognosis
• Proportional Hazards Models
• Prospective Studies
• Risk Factors
• Smoking (adverse effects, epidemiology)