Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers.
BACKGROUND
Obesity, diabetes mellitus, and glucose intolerance have been associated with increased pancreatic cancer risk; however, prediagnostic serum insulin concentration has not been evaluated as a predictor of this malignancy.


OBJECTIVE
To investigate whether prediagnostic fasting glucose and insulin concentrations and insulin resistance are associated with subsequent incidence of exocrine pancreatic cancer in a cohort of male smokers.


METHODS
A case-cohort prospective study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1985-1988) cohort of 29,133 male Finnish smokers ages 50 to 69 years. The study included 400 randomly sampled subcohort control participants and 169 incident pancreatic cancer cases that occurred after the fifth year of follow-up. All participants were followed up through December 2001 (up to 16.7 years of follow-up).


METHODS
Incident exocrine pancreatic cancer identified from the Finnish Cancer Registry.


RESULTS
After adjusting for age, smoking, and body mass index, higher baseline fasting serum concentrations of glucose, insulin, and insulin resistance were positively associated with pancreatic cancer. The presence of biochemically defined diabetes mellitus (glucose, > or =126 mg/dL [> or =6.99 mmol/L]) and insulin concentration in the highest vs lowest quartile both showed a significant 2-fold increased risk (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.04-4.35; and HR, 2.01; 95% CI, 1.03-3.93; respectively). There were significant interactions for all the biomarker exposures by follow-up time, such that the positive associations were stronger among the cases that occurred more than 10 years after baseline (highest vs lowest quartile: glucose, HR, 2.16; 95% CI, 1.05-4.42; P for trend = .02; insulin, HR, 2.90; 95% CI, 1.22-6.92; P for trend = .005; and insulin resistance, HR, 2.71; 95% CI, 1.19-6.18; P for trend = .006).


CONCLUSIONS
These results support the hypothesis that exposure to higher insulin concentrations and insulin resistance predicts the risk of exocrine pancreatic cancer.
Stolzenberg-Solomon
Rachael Z
RZ
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Rockville, Md 20852, USA. rs221z@nih.gov
Graubard
Barry I
BI
Chari
Suresh
S
Limburg
Paul
P
Taylor
Philip R
PR
Virtamo
Jarmo
J
Albanes
Demetrius
D
D001786:Blood Glucose / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000453:epidemiology* / Q000209:etiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D001786:Blood Glucose; D007328:Insulin