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


CONCLUSIONS
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.
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. lmucci@hsph.harvard.edu
Lorelei A
LA
Mucci
Jennifer R
JR
Stark
Michael N
MN
Pollak
Haojie
H
Li
Tobias
T
Kurth
Meir J
MJ
Stampfer
Jing
J
Ma
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood*; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood*; D012307:Risk Factors
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I