Serum levels of C-peptide, IGFBP-1 and IGFBP-2 and endometrial cancer risk; results from the European prospective investigation into cancer and nutrition.
Cust AE., Allen NE., Rinaldi S., Dossus L., Friedenreich C., Olsen A., Tjønneland A., Overvad K., Clavel-Chapelon F., Boutron-Ruault MC., Linseisen J., Chang-Claude J., Boeing H., Schulz M., Benetou V., Trichopoulou A., Trichopoulos D., Palli D., Berrino F., Tumino R., Mattiello A., Vineis P., Quirós JR., Agudo A., Sánchez MJ., Larrañaga N., Navarro C., Ardanaz E., Bueno-de-Mesquita HB., Peeters PH., van Gils CH., Bingham S., Khaw KT., Key T., Slimani N., Riboli E., Kaaks R.
We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition, to examine the associations between prediagnostic serum concentrations of C-peptide, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-2, and endometrial cancer risk. Among pre- and post-menopausal women, who were not currently using exogenous hormones, 286 women developed incident endometrial cancer during an average 5.1 years follow-up. Using risk set sampling, 555 matched control subjects were selected. In conditional logistic regression models adjusted for matching factors only, endometrial cancer risk increased with increasing serum levels of C-peptide (relative risks (RR) for the top vs. bottom quartile = 2.13 [95% confidence interval (CI) 1.33-3.41], p(trend) = 0.001, and decreasing serum levels of IGFBP-2 (RR for the top vs. bottom quartile = 0.56 [95% CI 0.35-0.90], p(trend) = 0.03, but was not significantly associated with IGFBP-1 levels (RR for the top vs. bottom quartile = 0.76 [95% CI 0.47-1.21], p(trend) = 0.25). In BMI-adjusted models, only the C-peptide association remained marginally statistically significant (RR for the top vs. bottom quartile = 1.56 [95% CI 0.94-2.57], p(trend) = 0.05 for C-peptide; 0.84 [95% CI 0.50-1.40], p(trend) = 0.74 for IGFBP-2; and 1.08 [95% CI 0.65-1.78], p(trend) = 0.86 for IGFBP-1 levels). These associations were stronger among nonfasting women (< or =< or =6 hr since last meal; 63% of subjects) but were not evident among fasting women, although the interactions were not statistically significant. The C-peptide-risk association was substantially attenuated after adjustment for free estradiol in postmenopausal women (RR for the top vs. bottom quartile = 1.28 [95% CI 0.67-2.45], p(trend) = 0.42. Our results provide modest support to the hypothesis that hyperinsulinaemia is a risk factor for endometrial cancer.