Grant Number:	5R21CA098348-02 Interpret this number
Primary Investigator:	Fowke, Jay
Organization:	Vanderbilt University
Project Title:	Adipose-Related Biomarkers of Prostate Cancer
Fiscal Year:	2004

DESCRIPTION (provided by applicant) Adipocytes highly express the GYP19 gene encoding aromatase, an enzyme responsible for metabolizing androgens (e.g., testosterone) to estrogen (E). Estrogens activate estrogen and androgen receptors in prostate cells, and E exposure may permit cancer of the prostate (CAP) to progress to clinical detection and androgen-independence. Recently, a preliminary investigation found the Arg264Cys polymorphism in CYP19 associated with increased CaP risk, suggesting that body adiposity affects prostate carcinogenesis by altering the androgen/estrogen balance. However, epidemiologic studies provide little support for a relationship between obesity and CaP, perhaps because it is difficult to estimate body adiposity in large epidemiologic studies. Our multi-disciplinary team from the fields of nutritional epidemiology, pathology, medical genetics, molecular biology, and urology propose to investigate the role of adipose and estrogen related biomarkers in prostate carcinogenesis. Toward this goal, this pilot molecular epidemiologic study aims to recruit men undergoing confirmatory diagnostic tests for CaP. Fasting blood samples will be collected, and diet, physical activity, body size, and other CaP risk factors will be measured during pretreatment interviews. The recruitment base includes clinical centers serving the African-American population of Nashville, TN. With the endorsement of clinical staff we expect to recruit 70% of all biopsy patients at these centers, providing 250 CaP cases during one year. A control group (n=250), matched to the age and race distribution of the case group, will be selected from men without CaP at biopsy. Bias in the analysis may be reduced by excluding controls with latent CaP, systematic data collection by trained interviewers, and analysis of pre-treatment blood samples. The association between CaP and CYP19 genetic polymorphisms (Arg264Cys, allele length) will be investigated using multivariable logistic regression controlling for genetic susceptibility to adipocyte differentiation (the Pro12Ala polymorphism of peroxisome proliferator activated receptor- y2), body adiposity (blood leptin), insulin resistance (blood insulin and Cpeptide), diet, physical activity, and other potential CaP risk factors. Greater body adiposity may advance prostate carcinogenesis through an estrogen mechanism, and an analysis of adipose-related biomarkers may suggest that weight reduction would decrease CaP risk or improve prognosis.





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