Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3.
BACKGROUND
Insulin-like growth factor-I (IGF-I) is a potent mitogen for normal and neoplastic cells, whereas IGF-binding protein-3 (IGFBP-3) inhibits cell growth in many experimental systems. Acromegalics, who have abnormally high levels of growth hormone and IGF-I, have higher rates of colorectal cancer. We therefore examined associations of plasma levels of IGF-I and IGFBP-3 with the risk of colorectal cancer in a prospective case-control study nested in the Physicians' Health Study.


METHODS
Plasma samples were collected at baseline from 14916 men without diagnosed cancer. IGF-I, IGF-II, and IGFBP-3 were assayed among 193 men later diagnosed with colorectal cancer during 14 years of follow-up and among 318 age- and smoking-matched control subjects. All P values are two-sided.


RESULTS
IGFBP-3 levels correlated with IGF-I levels (r=.64) and with IGF-II levels (r=.90). After controlling for IGFBP-3, age, smoking, body mass index (weight in kg/[height in m]2), and alcohol intake, men in the highest quintile for IGF-I had an increased risk of colorectal cancer compared with men in the lowest quintile (relative risk [RR]=2.51; 95% confidence interval [CI]=1.15-5.46; P for trend = .02). After controlling for IGF-I and other covariates, men with higher IGFBP-3 had a lower risk (RR=0.28; 95% CI=0.12-0.66; P for trend = .005, comparing extreme quintiles). The associations were consistent during the first and the second 7-year follow-up intervals and among younger and older men. IGF-II was not associated with risk.


CONCLUSIONS
Our findings suggest that circulating IGF-I and IGFBP-3 are related to future risk of colorectal cancer.
Ma
J
J
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Jing.Ma@channing.harvard.edu
Pollak
M N
MN
Giovannucci
E
E
Chan
J M
JM
Tao
Y
Y
Hennekens
C H
CH
Stampfer
M J
MJ
D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood*; 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; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II