title: Finasteride modifies the relation between serum C-peptide and prostate cancer risk: results from the Prostate Cancer Prevention Trial.
abstract: Hyperinsulinemia and obesity-related metabolic disturbances are common and have been associated with increased cancer risk and poor prognosis. To investigate this issue in relation to prostate cancer, we conducted a nested case-control study within the Prostate Cancer Prevention Trial (PCPT), a randomized, placebo-controlled trial testing finasteride versus placebo for primary prevention of prostate cancer. Cases (n = 1,803) and controls (n = 1,797) were matched on age, PCPT treatment arm, and family history of prostate cancer; controls included all eligible non-whites. Baseline bloods were assayed for serum C-peptide (marker of insulin secretion) and leptin (an adipokine) using ELISA. All outcomes were biopsy determined. Logistic regression calculated odds ratios (OR) for total prostate cancer and polytomous logistic regression calculated ORs for low-grade (Gleason <7) and high-grade (Gleason >7) disease. Results were stratified by PCPT treatment arm for C-peptide. For men on placebo, higher versus lower serum C-peptide was associated with a nearly 2-fold increased risk of high-grade prostate cancer (Gleason >7; multivariate-adjusted OR, 1.88; 95% confidence interval, 1.19-2.97; P(trend) = 0.004). When C-peptide was modeled as a continuous variable, every unit increase in log(C-peptide) resulted in a 39% increased risk of high-grade disease (P = 0.01). In contrast, there was no significant relationship between C-peptide and high-grade prostate cancer among men receiving finasteride. Leptin was not independently associated with high-grade prostate cancer. In conclusion, these results support findings from other observational studies that high serum C-peptide and insulin resistance, but not leptin, are associated with increased risk of high-grade prostate cancer. Our novel finding is that the C-peptide-associated risk was attenuated by use of finasteride.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA. mneuhous@fhcrc.org
authors.forename: Marian L
authors.initials: ML
authors.lastname: Neuhouser
authors.forename: Cathee
authors.initials: C
authors.lastname: Till
authors.forename: Alan
authors.initials: A
authors.lastname: Kristal
authors.forename: Phyllis
authors.initials: P
authors.lastname: Goodman
authors.forename: Ashraful
authors.initials: A
authors.lastname: Hoque
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.forename: Ann W
authors.initials: AW
authors.lastname: Hsing
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Howard L
authors.initials: HL
authors.lastname: Parnes
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
mesh_terms: D002096:C-Peptide / Q000097:blood*; D016022:Case-Control Studies; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D018120:Finasteride / Q000627:therapeutic use*; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000517:prevention & control*; D012307:Risk Factors
chemical_list: D002096:C-Peptide; D004791:Enzyme Inhibitors; D020738:Leptin; D018120:Finasteride