Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.
BACKGROUND
Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation, proliferation and apoptosis, and may have a role in the aetiology of various cancers. Information on their role in pancreatic cancer is limited and was examined here in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition.


METHODS
Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in 422 cases and 422 controls matched on age, sex, study centre, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounding variables.


RESULTS
Neither circulating levels of IGF-I (OR=1.21, 95% CI 0.75-1.93 for top vs bottom quartile, P-trend 0.301), IGFBP-3 (OR=1.00, 95% CI 0.66-1.51, P-trend 0.79), nor the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level (OR=1.22, 95% CI 0.75-1.97, P-trend 0.27), were statistically significantly associated with the risk of pancreatic cancer. In a cross-classification, however, a high concentration of IGF-I with concurrently low levels of IGFBP-3 was related to an increased risk of pancreatic cancer (OR=1.72, 95% CI 1.05-2.83; P-interaction=0.154).


CONCLUSIONS
On the basis of these results, circulating levels of components of the IGF axis do not appear to be the risk factors for pancreatic cancer. However, on the basis of the results of a subanalysis, it cannot be excluded that a relatively large amount of IGF-1 together with very low levels of IGFBP-3 might still be associated with an increase in pancreatic cancer risk.
Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, University of Zurich, Hirschengraben 84, Zürich 8001, Switzerland. sabine.rohrmann@ifspm.uzh.ch
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Rohrmann
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Grote
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Becker
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Rinaldi
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Tjønneland
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Roswall
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Grønbæk
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Overvad
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Boutron-Ruault
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Clavel-Chapelon
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Racine
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Teucher
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Boeing
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Drogan
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Dilis
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Lagiou
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Trichopoulou
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Palli
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Tagliabue
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Tumino
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Vineis
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Mattiello
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Rodríguez
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Duell
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Molina-Montes
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Dorronsoro
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Huerta
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Ardanaz
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Jeurnink
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Peeters
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Lindkvist
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Johansen
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Sund
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Khaw
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Wareham
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Allen
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Crowe
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Fedirko
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Jenab
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Michaud
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Norat
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Riboli
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Bueno-de-Mesquita
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Kaaks
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004032:Diet; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008019:Life Style; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010190:Pancreatic Neoplasms / Q000453:epidemiology*; D012307:Risk Factors
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I