Insulin, glucose, insulin resistance, and incident colorectal cancer in male smokers.
OBJECTIVE
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.
Limburg
Paul J
PJ
Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. limburg.paul@mayo.edu
Stolzenberg-Solomon
Rachael Z
RZ
Vierkant
Robert A
RA
Roberts
Katherine
K
Sellers
Thomas A
TA
Taylor
Philip R
PR
Virtamo
Jarmo
J
Cerhan
James R
JR
Albanes
Demetrius
D
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D015994:Incidence; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology*
D014408:Biomarkers, Tumor; D001786:Blood Glucose; D007328:Insulin