Serum C-peptide, insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women.

Abstract

BACKGROUND:

Leading a Western lifestyle, being overweight, and being sedentary are associated with an increased risk of colorectal cancer. Recent theories propose that the effects of these risk factors may be mediated by increases in circulating insulin levels and in the bioactivity of insulin-like growth factor (IGF)-I. To test this hypothesis, we conducted a case-control study nested within a cohort of 14 275 women in New York.

METHODS:

We used blood samples that had been obtained from these women from March 1985 through June 1991 and stored in a biorepository. C-peptide (a marker for insulin secretion), IGF-I, and IGF-binding proteins (IGFBPs)-1, -2, and -3 were assayed in the serum of 102 women who subsequently developed colorectal cancer and 200 matched control subjects. Logistic regression was used to relate cancer risk to these peptide levels, by adjustment for other risk factors. All statistical tests used are two-sided.

RESULTS:

Colorectal cancer risk increased with increasing levels of C-peptide (P:(trend) =.001), up to an odds ratio (OR) of 2. 92 (95% confidence interval [CI] = 1.26-6.75) for the highest versus the lowest quintiles, after adjustment for smoking. For colon cancer alone (75 case subjects and 146 control subjects), ORs increased up to 3.96 (95% CI = 1.49-10.50; P:(trend) <.001) for the highest versus the lowest quintiles. A statistically significant decrease in colorectal cancer risk was observed for increasing levels of IGFBP-1 (P:(trend) =.02; OR in the upper quintile = 0.48 [95% CI = 0.23-1. 00]), as well as for the highest quintile of IGFBP-2 levels (P:(trend) =.06; OR = 0.38 [95% CI = 0.15-0.94]). Colorectal cancer risk showed a modest but statistically nonsignificant positive association with levels of IGF-I and was statistically significantly increased for the highest quintile of IGFBP-3 (OR = 2.46 [95% CI = 1. 09-5.57]).

CONCLUSIONS:

Chronically high levels of circulating insulin and IGFs associated with a Western lifestyle may increase colorectal cancer risk, possibly by decreasing IGFBP-1 and increasing the bioactivity of IGF-I.

• Authors: R Kaaks, P Toniolo, A Akhmedkhanov, A Lukanova, C Biessy, H Dechaud, S Rinaldi, A Zeleniuch-Jacquotte, R E Shore, E Riboli
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 92 Issue 19 Pg. 1592-600 (Oct 04 2000) ISSN: 0027-8874 [Print] United States
• PMID: 11018095 (Publication Type: Journal Article)

Chemical References

• C-Peptide
• Insulin-Like Growth Factor Binding Protein 1
• Insulin-Like Growth Factor Binding Protein 2
• Insulin-Like Growth Factor Binding Protein 3
• Insulin-Like Growth Factor Binding Proteins
• Insulin-Like Growth Factor I

Topics

• Adult
• Body Mass Index
• C-Peptide (blood)
• Case-Control Studies
• Colorectal Neoplasms (blood, etiology)
• Female
• Humans
• Insulin-Like Growth Factor Binding Protein 1 (blood)
• Insulin-Like Growth Factor Binding Protein 2 (blood)
• Insulin-Like Growth Factor Binding Protein 3 (blood)
• Insulin-Like Growth Factor Binding Proteins (blood)
• Insulin-Like Growth Factor I (metabolism)
• Logistic Models
• Middle Aged
• New York
• Odds Ratio
• Prospective Studies
• Risk
• Risk Factors