© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 7, 620-625,
April 7, 1999
© 1999 Oxford University Press
REPORTS |
Prospective Study of Colorectal Cancer Risk in Men and Plasma Levels of Insulin-Like Growth Factor (IGF)-I and IGF-Binding Protein-3
Affiliations of authors: J. Ma, Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston MA; M. N. Pollak, Y. Tao, Departments of Medicine and Oncology, Cancer Prevention Research Unit, Lady Davis Research Institute of the Jewish General Hospital and McGill University, Montreal, Canada; E. Giovannucci, Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School and Department of Nutrition, Harvard School of Public Health, Boston; J. M. Chan, Department of Epidemiology, Harvard School of Public Health; C. H. Hennekens, Department of Epidemiology, Harvard School of Public Health and Division of Preventive Medicine, Departments of Medicine and Ambulatory Care and Prevention, Brigham and Women's Hospital and Harvard Medical School; M. J. Stampfer, Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School and Departments of Nutrition and Epidemiology, Harvard School of Public Health.
Correspondence to: Jing Ma, M.D., Ph.D., Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave., Boston, MA 02115 (e-mail: Jing.Ma{at}channing.harvard.edu).
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 14 916 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.
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