Serum levels of C‐peptide, IGFBP‐1 and IGFBP‐2 and endometrial cancer risk; Results from the European prospective investigation into cancer and nutrition

Abstract

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 Cpeptide, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-2, and endometrial cancer risk. Among pre-and postmenopausal 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. . These associations were stronger among nonfasting women ( 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 5 1.28 [95% CI 0.67-2.45], p trend 5 0.42. Our results provide modest sup-

Tumor necrosis factor (TNF)‐α, soluble TNF receptors and endometrial cancer risk: The EPIC study

“…7,8 Briefly, women who did not use exogenous hormones at blood donation, who did not report hysterectomy or who did not have a previous diagnosis of cancer (except nonmelanoma skin cancer) were eligible for the study. The 270 incident epithelial endometrial cancer cases selected included 65 cases in Denmark, 57 in Italy, 41 in Spain, 33 in the United Kingdom, 33 in the Netherlands,…”

“…Serum sex hormones and C-peptide had been measured previously. 7,8 Odds ratios for endometrial cancer in relation to quartiles of TNF-a or sTNFRs were calculated by conditional logistic regression. Likelihood ratio tests were used to assess linear trends in ORs with assigned quantitative scores for the quartiles (cut-off points based on the distributions of the controls).…”

A Prospective Evaluation of Insulin and Insulin-like Growth Factor-I as Risk Factors for Endometrial Cancer

“…This is critical, given the mutual association of hyperinsulinemia and high estrogen levels with obesity. Two recent prospective investigations of endometrial cancer that lacked fasting blood specimens reported positive associations between C-peptide levels (a marker of pancreatic insulin secretion) and endometrial cancer risk (10,11), including one that also controlled for endogenous estrogen levels (10). In that study, adjustment for free estradiol levels attenuated the positive association of C-peptide with endometrial cancer.…”

Body Mass Index, Hormone Replacement Therapy, and Endometrial Cancer Risk: A Meta-Analysis

“…The potential role of obesity-associated chronic hyperinsulinemia is supported by observations that high insulin levels are associated with increased endometrial cancer risk (72,73). Chronic hyperinsulinemia also increases synthesis of androgen precursors peripherally, and as elevated plasma androstenedione and testosterone concentrations increase endometrial cancer risk in pre and postmenopausal women (69), hypersulinemia may be relevant in this cancer independent of menopausal status.…”