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Insulin and Insulin-like Growth Factor Biomarkers and Prognosis of Prostate Cancer-specific Mortality

Principal Investigator
Name
Jing Ma
Degrees
-
Institution
Brigham & Women Hospital
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2011-0181
Initial CDAS Request Approval
Nov 14, 2011
Title
Insulin and Insulin-like Growth Factor Biomarkers and Prognosis of Prostate Cancer-specific Mortality
Summary
ABSTRACT: One of the overarching challenges in prostate cancer (PC) research is to distinguish aggressive from indolent disease. Current treatment decision for men with localized PC has been primarily depend on PSA, T-category, and Gleason score to determine appropriate treatment. Because of our limited ability to identify which men will progress and die of the disease, most of these men opt for radical treatment, causing many men to be over-treated and suffer from associated side effects. It is therefore clear that additional biologically relevant markers are urgently needed to improve prognostication above and beyond clinical characteristics. We have recently found that in the Harvard cohorts elevated BMI and plasma C-peptide levels (a marker of insulin production) were significantly predictive for PC-specific mortality (PCSM) independent of the DAmico risk and adding these risk factors to DAmico risksignificantly improved prediction of PCSM and all-cause mortality. We propose to use data from four cohorts of PC patients, the two Harvard cohorts, the American Cancer Society cohort, and the PLCO to conduct the following specific aims: 1. Among men who developed localized PC, we will continue our work on building and validating the best predictive model for PC-specific mortality and all-cause mortality with the biomarkers in combination with the DAmico risk or in the Kattan nomogram in the PHS and the HPFS (training set); 2. Validate these models using prediagnostic baseline blood samples in the ACS and PLCO cohorts (validation I); 3. We will then validate these models using blood samples collected at diagnosis among the ~4000 PC patients in the PLCO, when all the PC were detected by PSA screening (validation II). These well-characterized cohorts with blood samples collected before-, and at-diagnosis, the long-term complete follow-up of fatal PC and all-cause mortality provide an unique opportunity to independently validate our preliminary findings.
Aims

Hypothesis: We hypothesize that a host with systemic energetic dysregulation (overweight/obese and/or hyperinsulinemic) may prestage the microenvironment within distant tissues to receive incoming cancer cells, and that the host-tumor interaction could be crucial in promoting micometastasis (14-19). Primary Aims: 1. Among men who developed localized PC, we will continue our work on building and validating the best predictive model for PC-specific mortality and all-cause mortality with the biomarkers in combination with the DAmico risk or in the Kattan nomogram in the PHS and the HPFS (training set); 2. Validate these models using prediagnostic baseline blood samples in the ACS and PLCO cohorts (validation I); 3. We will then validate these models using blood samples collected at diagnosis among a subcohort of 30% of the ~4000 men with localized PC in the PLCO, when all the PC were detected by PSA screening (validation II). Secondary Aim: 4. we will conduct subgroup analyses to determine if the risk prediction of fatal prostate cancer differs by age at diagnosis, family history of PC and race, which may provide some insight into the racial disparity of this disease; 5. Meanwhile, we will evaluate lifestyle and dietary determinants of C-peptide and IGFs in these men. We will compare the predictability of baseline biomarkers to diagnostic biomarkers and, based on the results we will form the final recommendation for clinical prognosis of future fatal PC.

Collaborators

Sarah Daugherty (NCI DCEG)
Michael Pollak (McGill University)
Nancy R. Cook (Brigham & Womens Hospital)
PAUL L NGUYEN (Brigham & Womens Hospital)
weiliang Qiu (Brigham & Womens Hospital)
Regina Ziegler (NCI DCEG)
Mandy Black (NCI DCEG)
Orestis Panagiotou (NCI DCEG)
Yan Li (NCI DCEG)
Bob Hoover (NCI DCEG)

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