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SWOG SELECT-PCPT Biorepository: Specimen Use

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The projects below all make use of biospecimens and associated clinical data from the SWOG SELECT-PCPT biorepository. They were chosen in early 2011 through a peer-review process designed to encourage the development of novel translational research that uses these resources.

Approved Projects

Title: External validation of the PCPT calculator and the body mass index adjusted PCPT calculator
PI: Yuanyuan Liang, Ph.D.
Institution: University of Texas Health Sciences Center San Antonio

ABSTRACT (provided by applicant):
The PCPT prostate cancer risk calculator and the updated body mass index (BMI) adjusted PCPT calculator are available online for a man and his physician to assess his risk of prostate cancer if prostate biopsy were performed. The purposes of this study are to conduct external validation of the PCPT calculator and the BMI-adjusted PCPT calculator, and to assess the differences in diagnostic performance due to race and the effect of selenium and vitamin E, alone and in combination on the diagnostic performances of the original and the BMI-adjusted PCPT calculators using the participants in SELECT.


Title: Plasma Tocopherols and Risk of Prostate Cancer in SELECT
PI: Demetrius Albanes, M.D.
Institution: National Cancer Institute (NCI)

ABSTRACT (provided by applicant):
Although α-tocopherol supplementation did not reduce prostate cancer incidence in SELECT or the Physicians' Health Study-II, observational data as well as results from the ATBC Study of smokers (1) indicate that risk reduction with either circulating or supplemental α-tocopherol may be limited to advanced cases, or to current/former smokers. Data from prospective serologic studies of vitamin E and prostate cancer risk complement controlled supplementation trial data. We propose to determine whether baseline circulating tocopherols are prospectively associated with prostate cancer risk in the SELECT prostate cancer case-cohort study. Possible interactions with smoking, trial interventions, and race will be specifically tested.


Title: Plasma 25(OH)-Vitamin D and Risk of Prostate Cancer in SELECT
PI: Demetrius Albanes, M.D.
Institution: National Cancer Institute (NCI)

ABSTRACT (provided by applicant):
There is substantial interest in cancer prevention properties of vitamin D. Nested case-control studies of prostate cancer risk and circulating 25-hydroxyvitamin D (25(OH)D), the accepted biomarker of vitamin D status, have been inconclusive, however. Given trends toward high dose vitamin D supplementation and the clinical significance of prostate cancer, a more definitive understanding of vitamin D status and prostate cancer is needed. We propose to determine whether baseline circulating 25(OH)D is prospectively associated with prostate cancer risk in the SELECT prostate cancer case-cohort study. Possible interactions with the SELECT vitamin E and selenium interventions and race will be specifically tested.


Title: Methionine Metabolism and Prostate Cancer: Prospective Analyses in SELECT and PCPT
PI: Jay Fowke, Ph.D.
Institution: Vanderbilt University Medical Center

ABSTRACT (provided by applicant):
Recent reports suggest sarcosine may be a valuable marker of aggressive prostate cancer. However, our preliminary data suggest a broader role of methionine metabolism in prostate cancer, regulated by glycine N-methyltransferase (GNMT) and other candidate genes responsible for the availability of methyl donors such as S- adenosylmethionine (SAM). We will use data and biospecimens collected within SELECT and PCPT to determine and validate the association between plasma and genetic markers of methionine metabolism and prostate cancer. Our results may identify a metabolic target for behavioral or drug strategies to reduce prostate cancer treatment burden or improve prognosis.


Title: Prospective Evaluation of Intraprostatic Inflammation and Focal Atrophy in Men without an Indication for Biopsy in the Etiology of Prostate Cancer
PI: Elizabeth Platz, Sc.D., M.P.H.
Institution: John Hopkins Bloomberg School of Public Health

ABSTRACT (provided by applicant):
We hypothesize that chronic intraprostatic inflammation and focal atrophy cause prostate cancer. To address this hypothesis, we propose to link PCPT and SELECT to form a new cohort: men negative for prostate cancer on PCPT end-of-study biopsy who later enrolled in SELECT. Using biopsy tissue, we will evaluate prostate cancer risk in association with the 1) prevalence/extent of inflammatory infiltrates and type of immune cells; and 2) prevalence/extent, morphologic type, and biological characteristics of focal atrophy. Findings from this prospective study may have important clinical and public health implications for preventing the most commonly diagnosed cancer in US men.


Title: A Functional Variant in NKX3.1 as a Predictor for Success in the Antioxidant Chemoprevention of Prostate Cancer
PI: Sarki Abdulkadir, M.D.
Institution: Vanderbilt University Medical Center

ABSTRACT (provided by applicant):
We propose a functional variant in the prostate tumor suppressor gene NKX3.1 as a biomarker for predicting the response to antioxidant chemoprevention for prostate cancer. NKX3.1 regulates ROS levels in the prostate, and Nkx3.1 -/- mice develop prostatic intraepithelial neoplasia. Antioxidant exposure is widely believed to reduce prostate cancer risk, but surprisingly, antioxidant treatment increased prostatic epithelial proliferation in Nkx3.1 -/- mice. This functional NKX3.1 variant decreases human prostate NKX3.1 expression, and based on our animal research we hypothesize that SELECT and PCPT participants with the NKX3.1 risk allele and low oxidative stress levels will be at increased risk of developing prostate cancer.


Title: Selenium Supplementation and Risk of Diabetes and Other Cardio-Metabolic Abnormalities
PI: Alan Kristal, Ph.D.
Institution: Fred Hutchinson Cancer Research Center

ABSTRACT (provided by applicant):
Multiple studies have found increased risks of diabetes and hyperlipidemias associated with high serum selenium (Se). This proposal examines whether Se supplementation was associated with pre-clinical progression of diabetes, dyslipidemias and hypertension, measured by changes in biomarkers (HbA1c, total:HDL cholesterol, ApoB:ApoA1, systolic and diastolic blood pressure) between baseline and approximately year 5 post-randomization. This study also examines whether Se supplementation was associated with clinical outcomes, including diabetes, hypercholesterolemia, and hypertension, expanding upon previously published analyses. Analyses will test whether effects of Se supplementation were larger among men with high baseline serum Se. Results of this study may have high public health impact.
 
     
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