Prediagnostic BMI, Plasma C-Peptide Concentration, And Prostate Cancer-Specific Mortality In Men With Prostate Cancer: A Long-Term Survival Analysis

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 24 Nov 2008 - 3:00 PDT

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UroToday.com - A significant level of interest has developed in the association of prostate cancer (CaP) specific mortality (PCSM) with nutrition, lifestyle variables, and treatment effects. The data surrounding a man's body mass index (BMI) and PCSM is mixed, but likely suggest an association between high BMI and an increased risk of dying from CaP. But is there a test that links obesity with this increased risk? In the online edition of Lancet Oncology, Dr. Jing Ma and associates of Dr. Ed Giovannucci report that plasma concentrations of C-peptide and obesity predispose men with a subsequent diagnosis of CaP to a greater likelihood of PCSM.

The C-peptide link is based upon the fact that obesity causes metabolic changes to include hyperinsulinemia. C-peptide is a marker of insulin secretion that can be measured in plasma. This study assesses the role of pre-diagnostic BMI and C-peptide concentration in PCSM in the Physicians' Health Study, a randomized trial of aspirin and beta carotene in 22,071 US male physicians aged 40-84 in 1982. None had heart disease or major chronic illnesses. BMI was calculated at baseline and at the eighth year of follow-up. BMI was categorized as healthy, overweight or obese. Between 1982 and 1984, 14,916 men gave blood samples and 827 were assayed for C-peptide and 718 for PSA. The researchers assessed the predictors of lethal CaP and other potential confounding variables by BMI categories.

During the follow-up period, 2,546 men were diagnosed with CaP; 989 (38.8%) were overweight and 87 (3.4%) were obese. More obese men were past smokers and more likely to have extraprostatic or metastatic CaP or high Gleason grade tumors at diagnosis. BMI was not related to PSA concentration, which is important as other studies have suggested the increased circulating plasma volumes in obese men decrease their measurable PSA levels. Higher baseline C-peptide levels correlated with older age. During 24 years of follow-up, 281 of 2,546 men (11%) died from CaP and 485 (19%) died from other causes. A higher baseline BMI was significantly associated with a higher risk of PCSM, independent of age at diagnosis and baseline smoking status, compared with a healthy BMI (hazard ratio 1.47 for overweight men and 2.66 for obese men). This remained statistically significant after controlling for clinical stage and Gleason grade. Further controlling for PSA strengthened the association of being overweight (HR1.8), but attenuated the association for obesity (HR 1.6). Interestingly, among men diagnosed during the pre-PSA era, 33.7% died from CaP compared to 6.6% in the PSA screening era.

Among 117 men who died from CaP, a significantly higher proportion (21.4%) had baseline C-peptide in the highest quartile (HR 2.38 for PCSM) compared to the lowest quartile. The inclusion of BMI and clinical predictors in the same model attenuated the associations for both BMI and C-peptide concentrations, suggesting that part of the effect of BMI on CaP prognosis is mediated by insulin. Looking at the joint association between BMI and C-peptide concentration, increased risk of PCSM associated with higher concentrations of C-peptide was significant in overweight and obese men, but not in healthy men. Overweight men with C-peptide levels in the highest quartile were over four-times more likely to die from CaP than men of a healthy weight and with C-peptide levels in the lowest quartile.

Ma J, Li H, Giovannucci E, Mucci L, Qiu W, Nguyen PL, Gaziano JM, Pollak M, Stampfer MJ
Lancet Oncol. 2008 Oct 3. Epub ahead of print.
doi:10.1016/S1470-2045(08)70235-3

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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