Serum IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio and risk of pancreatic cancer in the prostate, lung, colorectal, and ovarian cancer screening trial.
BACKGROUND
Experimental evidence suggests that an overexpression of insulin-like growth factor (IGF)-I is implicated in human pancreatic tumors. Increased IGF-II and decreased IGF binding protein (IGFBP)-3 serum concentrations have been linked to a number of other cancers.


METHODS
We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort of men and women 55 to 74 years of age at baseline to test whether prediagnostic circulating IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio concentrations were associated with exocrine pancreatic cancer risk. Between 1994 and 2006, 187 incident cases of pancreatic adenocarcinoma occurred (follow-up of up to 11.7 years). Two controls (n = 374), who were alive at the time the case was diagnosed, were selected for each case and matched by age, race, sex, and date of blood draw. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) with the use of conditional logistic regression, adjusting for smoking.


RESULTS
IGF-I, IGF-II, and IGFBP-3 concentrations were not significantly associated with pancreatic cancer (highest compared with lowest quartile: OR, 1.58; 95% CI, 0.91-2.76; and P-trend = 0.25; OR, 0.86; 95% CI, 0.49-1.50; and P-trend = 0.31; and OR, 0.88; 95% CI, 0.51-1.51; and P-trend = 0.47, respectively). However, a significant positive trend was observed with high IGF-I/IGFBP-3 molar ratio levels (highest compared with lowest quartile: OR, 1.54; 95% CI, 0.89-2.66; P-trend = 0.04).


CONCLUSIONS
A higher IGF-I/IGFBP-3 molar ratio represents increased free IGF-I, which may be a risk factor for pancreatic cancer.


CONCLUSIONS
Our results highlight the importance of this biomarker for further investigation in large prospective cohort studies and pooled analysis with other prospective cohorts.
Douglas
Jason B
JB
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Rockville, Maryland, USA.
Silverman
Debra T
DT
Pollak
Michael N
MN
Tao
Yuzhen
Y
Soliman
Amr S
AS
Stolzenberg-Solomon
Rachael Z
RZ
D000230:Adenocarcinoma / Q000097:blood; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood*; D012307:Risk Factors
D014408:Biomarkers, Tumor; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II