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

Background: Leading a Western lifestyle, being overweight, and being sedent ary are associated with an increased risk of colorectal cancer. Recent theo ries propose that the effects of these risk factors may be mediated by incr eases 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 thro ugh June 1991 and stored in a biorepository. C-peptide (a marker for insuli n secretion), IGF-I, and IGF-binding proteins (IGFBPs)-1, -2, and -3 were a ssayed in the serum of 102 women who subsequently developed colorectal canc er 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 od ds ratio (OR) of 2.92 (95% confidence interval [CI] = 1.26-6.75) for the hi ghest 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; Pt-rend <.001) for the highest versus the low est quintiles, A statistically significant decrease in colorectal cancer ri sk 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 qui ntile of IGFBP-2 levels (P-trend = .06; OR = 0.38 [95% CI = 0.15-0.94]). Co lorectal cancer risk showed a modest but statistically nonsignificant posit ive association with levels of IGF-I and was statistically significantly in creased 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 ass ociated with a Western lifestyle may increase colorectal cancer risk, possi bly by decreasing IGFBP-1 and increasing the bioactivity of IGF-I.