Risk of ovarian cancer in relation to prediagnostic levels of C-peptide, insulin-like growth factor binding proteins-1 and -2 (USA, Sweden, Italy)

Objective: To investigate the association of prediagnostic circulating levels of C-peptide, as a marker of pancreatic insulin secretion, and IGF binding proteins -1 and -2, as indicators of the biologically active IGF-I concentration, with risk of developing ovarian cancer. Methods: The study was nested within three prospective cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). Case subjects were 132 women with primary invasive epithelial ovarian cancer diagnosed at least one year after blood donation. For each case, two control subjects were selected, matching the case subject on cohort, menopausal status, age and date of recruitment (n = 263). Only women who did not use exogenous hormones at blood donation were included in the study. Results: Odds ratios and their 95% confidence intervals for risk of developing ovarian cancer over quartiles of peptides concentrations after adjustment for BMI and fasting were: 1.00, 0.66 (0.35–1.23), 0.96 (0.51–1.82) and 0.89 (0.44–1.81) for C-peptide; 1.00, 1.10 (0.58–2.09), 1.07 (0.55–2.04) and 0.79 (0.38–1.62) for IGFBP-1; and 1.00, 1.01 (0.54–1.89), 0.98 (0.51–1.88) and 0.87 (0.45–1.68) for IGFBP-2. In women who had ovarian cancer diagnosis before age 55 the ORs for the top tertiles of IGFBP-1 and IGFBP-2 were 0.51 (0.18–1.49) and 0.53 (0.18–1.54), respectively. Conclusions: This study does not support an independent direct etiological role of C-peptide in ovarian cancer pathogenesis, but suggests a possible protective effect of circulating IGFBP-1 and -2 in women who develop ovarian cancer before age 55.