Insulin-like growth factor-I and insulin are associated with the presence and advancement of adenomatous polyps.
OBJECTIVE
Insulin and insulin-like growth factor-I (IGF-I) affect proliferation, differentiation, and apoptosis and are potential risk factors for colorectal cancer (CRC). Visceral obesity, possibly via hyperinsulinemia, has also been linked to CRC risk. We evaluated the relationship of insulin, IGF-I, insulin-like growth factor binding protein (IGFBP) 3, and visceral adipose tissue (VAT) in subjects with adenomatous polyps, the precursor lesion of colorectal cancer.


METHODS
Participants were asymptomatic subjects who underwent screening flexible sigmoidoscopy (FSG) within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Subjects underwent single-slice, computerized tomography scanning to measure VAT and serum fasting insulin, IGF-I, and IGFBP-3 measurements.


RESULTS
Four hundred fifty-eight subjects were enrolled, of which 202 subjects had an adenoma, 70 of which were an advanced adenoma. IGF-I (P = .02), IGF-I/IGFBP-3 ratio (P = .003), and insulin (P = .02) were significantly increased in subjects with adenomas compared with controls. In an unadjusted logistic regression analysis using sex-specific quartile cut points, subjects in quartile 4 in comparison with quartile 1 of IGF-I (odds ratio [OR] = 1.7; [95% CI: 1.0-2.9], Ptrend = .03), IGF-I/IGFBP-3 ratio (OR = 1.9 [95% CI: 1.1-3.3], Ptrend = .01), and insulin (OR = 2.1 [95% CI: 1.2-3.6], Ptrend = .04) were at increased risk of adenoma. When limiting the case group to advanced adenomas, the effect was more pronounced: IGF-I (OR = 2.8 [95% CI: 1.3-6.2], Ptrend = .006), IGF-I/IGFBP-3 ratio (OR = 2.3, [95% CI: 1.0-5.2], Ptrend = .04), and insulin (OR = 2.3 [95% CI: 1.1-4.9], Ptrend = .14). Visceral adipose tissue was not associated with adenoma risk.


CONCLUSIONS
Levels of IGF-I, ratio of IGF-I/IGFBP-3, and insulin are associated with adenomas and even more so with advanced adenomas. These data support the hypothesis that insulin and IGF-I may contribute to the development and advancement of adenomatous polyps.
Schoen
Robert E
RE
Department of Medicine, University of Pittsburgh, Pennsylvania 15213, USA. rschoen@pitt.edu
Weissfeld
Joel L
JL
Kuller
Lewis H
LH
Thaete
F Leland
FL
Evans
Rhobert W
RW
Hayes
Richard B
RB
Rosen
Clifford J
CJ
D018256:Adenomatous Polyps / Q000097:blood / Q000453:epidemiology / Q000473:pathology*; D000273:Adipose Tissue / Q000378:metabolism; D017677:Age Distribution; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D001707:Biopsy, Needle; D015331:Cohort Studies; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000097:blood / Q000453:epidemiology / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis / Q000097:blood*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000032:analysis / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D015995:Prevalence; D011336:Probability; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D017678:Sex Distribution; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3