Association between C-Peptide Concentration and Prostate Cancer Incidence in the CLUE II Cohort Study

Abstract

Diabetes, characterized by perturbations in insulin production and signaling, is inversely associated with prostate cancer risk irrespective of stage. Obesity, a diabetes risk factor, is inversely associated with localized disease but positively associated with advanced disease. To understand the complex association between hyperinsulinemia and prostate cancer, we evaluated the association of plasma C-peptide, an insulin secretion marker, with prostate cancer risk in a case-control study nested in a prospective community cohort. Prostate cancer cases (n = 264) and matched controls (n = 264) were identified in the CLUE II cohort between 1989 (baseline) and 2002. C-peptide concentration was measured in baseline plasma by ELISA. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression, adjusting for being overweight or obese and family history. Median C-peptide concentration was lower in cases (1,180 pmol/L) than in controls (1,365 pmol/L; P = 0.03). Men in the highest (versus lowest) fourth of C-peptide had a lower risk for prostate cancer (OR, 0.65; 95% CI, 0.37-1.14; P-trend = 0.08), primarily localized disease (OR, 0.44; 95% CI, 0.19-1.03; P-trend = 0.04). Associations were similar to overall, when excluding cases diagnosed during the first 5 years of follow-up, men with diabetes, or men who had not had a prostate-specific antigen test. C-peptide concentration was inversely associated with subsequent diagnosis of prostate cancer, primarily localized disease, similar to the association for obesity. However, we cannot rule out detection bias that might result if men with higher C-peptide have lower prostate-specific antigen irrespective of whether prostate cancer is present or not. Cancer Prev Res; 3(10); 1334-41. ©2010 AACR.

Association of IL10 and Other immune response‐ and obesity‐related genes with prostate cancer in CLUE II

“…Consistent with this difference and as we have shown previously 23, cases also had a slightly lower C-peptide concentration, a marker of insulin secretion. Among prostate cancer cases, 68.7% were diagnosed as clinically organ-confined and 60.9% were low grade.…”

“…First degree family history of prostate cancer was obtained from the 1996 follow-up questionnaire, the first one after the brief baseline survey, which was available for 64.8% of men in the analysis. Plasma concentrations of total cholesterol (mg/dL), C-reactive protein (mg/L) 22, and C-peptide (pmol/L) 23 were measured previously using an enzymatic method 24 in a commercial laboratory; using an immunoturbidimetric assay (Roche Diagnostics, Indianapolis, IN), and ELISA (ALPCO Diagnostics, Windham, NH) in the laboratory of Dr. Nader Rifai at Children’s Hospital Boston, respectively.…”

Insulin use is not significantly predictive for prostate cancer mortality in diabetic patients: a 12‐year follow‐up study

“…However, a lack of association between insulin level and prostate cancer was noted in some earlier studies [13,14] and in another recently published Health Professionals Follow‐up Study in the USA, which showed that prostate cancer risk was not associated with long‐term exposure to diet with a high insulin response [15]. Interestingly, C‐peptide (a marker for insulin secretion) was found to be inversely associated with prostate cancer in a nested case–control study in the USA (even though the investigators could not rule out a possibility of detection bias) [16].…”

Prediagnostic plasma IGFBP‐1, IGF‐1 and risk of prostate cancer

“…However, direct epidemiologic evidence linking circulating insulin and prostate cancer risk is limited and mixed: a case-control 19 and a recent case-cohort study 20 observed positive associations, whereas three other prospective studies observed no association. 10,21,22 In addition, findings are inconclusive between Cpeptide, a marker for insulin secretion, and risk of prostate cancer, 14,[23][24][25] including a recent analysis in HPFS (highest vs. lowest quartile OR 5 1.05, 95% CI 5 0.82-1.34, p trend 5 0.95). 14 The modulation of IGF-1 activity by IGFBP-1 is complex.…”