Plasma levels of acid-labile subunit, free insulin-like growth factor-I, and prostate cancer risk: a prospective study

Cancer Epidemiol Biomarkers Prev. 2010 Feb;19(2):484-91. doi: 10.1158/1055-9965.EPI-09-0836.


Background: The acid-labile subunit (ALS) acts in the insulin-like growth (IGF) system by binding circulating IGF-I in a ternary complex with binding protein (IGFBP)-3 to prevent IGF-I from crossing the endothelial barrier. Given the role of the IGF system in prostate cancer, ALS may influence carcinogenesis by modulating IGF-I levels or bioavailability.

Methods: We undertook a prospective study nested in the Physicians' Health Study to examine ALS, free IGF-I, and prostate cancer. We assayed circulating levels of ALS and IGF components among 545 incident cases and 545 matched controls. We calculated relative risks (RR) and 95% confidence intervals (95% CI) adjusted for life-style factors, total IGF-I, and IGFBP3.

Results: ALS was positively correlated with total IGF-I (r = 0.58), IGFBP3 (r = 0.68), and free IGF-I (r = 0.36). Comparing highest versus lowest quartiles, we found no association between free IGF-I and prostate cancer risk (RR, 0.9; 95% CI, 0.6-1.3). In contrast, ALS was positively associated with risk among men in the 2nd (RR, 1.5; 94% CI, 1.0-2.3), 3rd (RR, 1.6; 94% CI, 1.1-2.5), and 4th quartiles (RR, 1.4; 94% CI, 0.9-2.1) compared with lowest quartile. The association was stronger for advanced stage tumors (RR, 2.0; 94% CI, 0.8-4.6). There was a suggestion of an interaction between ALS and total IGF-I, whereby high circulating IGF-I was associated with an increased risk of advanced prostate cancer among men with low but not higher ALS levels.

Discussion: Plasma ALS is positively associated with prostate cancer risk, and may interact biologically with IGF-I to affect carcinogenesis. These data provide further support for the role of the IGF axis in prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Carrier Proteins / blood*
  • Glycoproteins / blood*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor I / analysis*
  • Male
  • Middle Aged
  • Prospective Studies
  • Prostatic Neoplasms / blood*
  • Risk Factors


  • Biomarkers, Tumor
  • Carrier Proteins
  • Glycoproteins
  • Insulin-Like Growth Factor Binding Protein 3
  • insulin-like growth factor binding protein, acid labile subunit
  • Insulin-Like Growth Factor I