Circulating insulin-like growth factor binding protein-1 and the risk of pancreatic cancer

Brian M. Wolpin, Dominique S. Michaud, Edward L. Giovannucci, Eva S. Schernhammer, Meir J. Stampfer, Joann E. Manson, Barbara B. Cochrane, Thomas E. Rohan, Jing Ma, Michael N. Pollak, Charles S. Fuchs

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Abstract

Insulin-like growth factor (IGF)-I has growth-promoting effects on pancreatic cancer cells, and elevated fasting serum insulin has been linked to pancreatic cancer risk. IGF binding protein-1 (IGFBP-1) is a downstream target of insulin and inhibits IGF-I activity. To investigate whether prediagnostic plasma levels of IGFBP-1 are associated with pancreatic cancer risk, we did a prospective, case-control study nested within the Health Professionals Follow-up Study, the Nurses' Health Study, the Physicians' Health Study, and the Women's Health Initiative. We assayed circulating IGFBP-1 among 144 pancreatic cancer cases that occurred ≥4 years after plasma collection and in 429 controls, matched for date of birth, prospective cohort, smoking status, and fasting status. When compared with participants in the three highest quartiles of plasma IGFBP-1, those in the lowest quartile experienced a relative risk (RR) for pancreatic cancer of 2.07 [95% confidence intervals (95% CI), 1.26-3.39], after adjusting for other risk factors, including circulating IGF-I, IGF binding protein-3, and C-peptide. Only participants in the lowest quartile of plasma IGFBP-1 showed an elevated risk of pancreatic cancer. The influence of low plasma IGFBP-1 became progressively stronger with time; among cases diagnosed ≥8 years after blood collection, the adjusted RR was 3.47 (95% CI, 1.48-8.14), comparing the bottom versus the top three quartiles. The influence of plasma IGFBP-1 was most marked among participants who never smoked cigarettes (RR, 3.30; 95% CI, 1.48-7.35). Among participants in four U.S. prospective cohort studies, low plasma IGFBP-1 levels significantly predicted an increased risk of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)7923-7928
Number of pages6
JournalCancer Research
Volume67
Issue number16
DOIs
StatePublished - Aug 15 2007

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Insulin-Like Growth Factor Binding Protein 1
Pancreatic Neoplasms
Blood Proteins
Insulin-Like Growth Factor I
Confidence Intervals
Fasting
Health
Insulin
Insulin-Like Growth Factor Binding Protein 3
C-Peptide
Women's Health
Protein C
Tobacco Products
Case-Control Studies
Cohort Studies
Smoking
Nurses
Parturition
Prospective Studies
Physicians

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Wolpin, B. M., Michaud, D. S., Giovannucci, E. L., Schernhammer, E. S., Stampfer, M. J., Manson, J. E., ... Fuchs, C. S. (2007). Circulating insulin-like growth factor binding protein-1 and the risk of pancreatic cancer. Cancer Research, 67(16), 7923-7928. https://doi.org/10.1158/0008-5472.CAN-07-0373

Circulating insulin-like growth factor binding protein-1 and the risk of pancreatic cancer. / Wolpin, Brian M.; Michaud, Dominique S.; Giovannucci, Edward L.; Schernhammer, Eva S.; Stampfer, Meir J.; Manson, Joann E.; Cochrane, Barbara B.; Rohan, Thomas E.; Ma, Jing; Pollak, Michael N.; Fuchs, Charles S.

In: Cancer Research, Vol. 67, No. 16, 15.08.2007, p. 7923-7928.

Research output: Contribution to journalArticle

Wolpin, BM, Michaud, DS, Giovannucci, EL, Schernhammer, ES, Stampfer, MJ, Manson, JE, Cochrane, BB, Rohan, TE, Ma, J, Pollak, MN & Fuchs, CS 2007, 'Circulating insulin-like growth factor binding protein-1 and the risk of pancreatic cancer', Cancer Research, vol. 67, no. 16, pp. 7923-7928. https://doi.org/10.1158/0008-5472.CAN-07-0373
Wolpin BM, Michaud DS, Giovannucci EL, Schernhammer ES, Stampfer MJ, Manson JE et al. Circulating insulin-like growth factor binding protein-1 and the risk of pancreatic cancer. Cancer Research. 2007 Aug 15;67(16):7923-7928. https://doi.org/10.1158/0008-5472.CAN-07-0373
Wolpin, Brian M. ; Michaud, Dominique S. ; Giovannucci, Edward L. ; Schernhammer, Eva S. ; Stampfer, Meir J. ; Manson, Joann E. ; Cochrane, Barbara B. ; Rohan, Thomas E. ; Ma, Jing ; Pollak, Michael N. ; Fuchs, Charles S. / Circulating insulin-like growth factor binding protein-1 and the risk of pancreatic cancer. In: Cancer Research. 2007 ; Vol. 67, No. 16. pp. 7923-7928.
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