© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 23, 1947-1948,
December 6, 2000
© 2000 Oxford University Press
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More About: 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: A. C. Paterson, G. S. Baldwin, A. Shulkes (Department of Surgery), K. S. Leeding, L. A. Bach (Department of Medicine), Austin and Repatriation Medical Centre, University of Melbourne, Australia; F. A. Macrae, Department of Gastroenterology, The Royal Melbourne Hospital.
Correspondence to: Professor Arthur Shulkes, D.Sc., Department of Surgery, Austin and Repatriation Medical Centre, University of Melbourne, Vic 3084, Australia (e-mail: aas{at}unimelb.edu.au).
Several recent epidemiologic studies (1–5) have implicated high levels of insulin-like growth factor-I (IGF-I) in plasma as a risk factor for prostate, breast, and colorectal cancers. The biologic evidence in favor of an important role for IGF-I in the development of colorectal and other cancers is strong (1,3,4). IGF-I stimulates transformation and inhibits apoptosis, IGF-I receptors and peptide are expressed by colorectal carcinomas (CRCs), and exogenous IGF-I stimulates proliferation of CRC cells. Two case–control studies (3,4) examined the relationship between IGF-I levels and CRC risk and concluded that an elevation in circulating IGF-I levels was associated with an increased risk of the disease. However, in both of these studies, the mean serum concentrations were similar in case and control subjects. A statistically significant increased risk was evident only when the subjects in the extreme upper and lower quintiles were compared (3,4). Renehan et al. (6) found no association between the presence of adenomas and the concurrent serum concentration of IGF-I.
We have taken a different approach and measured circulating IGF-I in subjects at risk of developing CRC because of either family history of CRC or the presence of polyps detected at colonoscopy. At the time of colonoscopy, blood was collected and IGF-I levels was measured in three groups of subjects: 1) subjects referred for colonoscopy subsequently shown to be negative for CRC (n = 34), 2) subjects with a family history of CRC (n = 62), and 3) subjects with a history of adenomatous polyps or polyps found at the colonoscopy (n = 78). [Relative risk of groups 2 and 3 of developing CRC increased twofold to sixfold compared with the average risk in the whole population (7).] Plasma IGF-I was measured by use of a radioimmunoassay (GroPep, Adelaide, Australia).
As shown in Table 1
, the mean concentration and 95% confidence intervals (CIs) of IGF-I in control subjects was 213 (95% CI = 180–247) ng/mL, which was not statistically significantly different from the subjects with a family history of CRC (202 [95% CI = 177–227] ng/mL) (P = .600) but was statistically significantly higher than the group with polyps (169 [149–189] ng/mL) (P = .019). Since IGF-I levels are inversely related to age (1–4), multivariate analysis was performed to compensate for the fact that the patients with polyps were older. There was still no evidence for an elevation of IGF-1 levels in the "high-risk" subjects (i.e., those with a positive history of polyps or a family history of CRC). The IGF-I concentrations adjusted for age were 202 (95% CI = 171–233) ng/mL (control), 190 (95% CI = 166–214) ng/mL (family history of CRC), and 183 (95% CI = 161–205) ng/mL (past or current polyps). There was no statistically significant difference between the three groups following adjustment for age (P = .501). When subjects were further subdivided to the highest risk category by selecting those with a family history of CRC plus the presence of polyps or history of adenomatous polyps, the IGF-I concentration (185 [95% CI = 154–215] ng/mL; n = 43) remained similar and not significantly different from the control value (P = .196). The IGF-I concentration in the polyp group was similar in patients with adenomatous (152 [95% CI = 127–177] ng/mL; n = 39) or nonadenomatous (186 [95% CI = 156–217] ng/mL; n = 39) polyps (P = .077).
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We conclude that concentrations of IGF-I in the plasma of patients at increased risk of developing CRC are no higher than concentrations in control subjects. The present results provide no support for the concept of identifying individuals with a high risk of developing CRC on the basis of circulating IGF-I concentrations. A similar conclusion has recently been reached with respect to prostate cancer (5).
REFERENCES
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Shaneyfelt T, Husein R, Bubley G, Mantzoros CS. Hormonal predictors of prostate cancer: a meta-analysis. J Clin Oncol 2000;18:847–53.
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Ma J, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, et al. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst 1999;91:620–5.
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Renehan AG, O'Dwyer ST, Shalet SM. Re: Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3 [letter]. J Natl Cancer Inst 1999;91:2051–2.
7 Australian Cancer Network. Guidelines for the prevention, early detection and management of colorectal cancer. National Health and Medical Research Council of Australia, Canberra (Australia): Commonwealth Government of Australia; 1999.
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