) Increasing evidence from epidemiologic and migration studies that dietary fat may increase the risk of developing prostate cancer (CaP) and progression to advanced disease. Our hypotheses are: 1) Androgens (and estrogen) and their metabolites are important modifiers of CaP initiation, progression and growth; 2) Dietary fat and fiber intake has an important impact on CaP progression and outcome with high fat/low fiber diets creating a favorable environment for cancer growth; 3) Diet, androgen metabolism and progression of CaP are linked. The adverse effects of high fat and low fiber intake are mediated via changes in androgen (and/or estrogen) metabolism; 4) Decreasing fat intake and increasing dietary fiber will alter sex steroid metabolism, change the micoenvironment within the prostate, and slow or prevent the progression of subclinical CaP to its more aggressive state.
The specific aim of the study is to examine androgens (and estrogens) levels, their intermediates, and metabolism in normal men (50 to 60 years) before and after dietary fat/fiber modulation. Forty men will be recruited where androgen (and estrogen) metabolism will be measured before and after 8 weeks of dietary modulation from the traditional American high fat (over 30 percenr of total caloric intake), low fiber (less than 20g/day) to a low fat (10 to 15 percent of total calories), high fiber (25 to 25g/day) diet. The specific parameters to be measured before and after diet modulation include: 1) circulating and urinary androgens and estrogens and their metabolites measured by radioimmunoassay and gas chromatography-mass spectroscopy respectively; 2) serum production and metabolic clearance rates of testerone (T) (determine after stable isotope labeled T infusion to steady state levels; 3) specific activity of labeled/unlabeled urinary metabolites of androgens during steady state infusions of stable isotope labeled T to determine the proportion of metabolites derived from T versus other substrates; 4) total energy expenditure determine by doubly labeled water method to characterize the effects of diet modulation on energy balances. These studies will characterize the effects of reducing fat and increasing fiber in the diet in androgen and estrogen metabolism. These data will provide the basis for future long term outcome studies to assess the effect of diet modulation of specific parameters of sex steroid metabolism and their impact on the development and progression of CaP in high risk population.
| Wang, Christina; Catlin, Don H; Starcevic, Borislav et al. (2005) Low-fat high-fiber diet decreased serum and urine androgens in men. J Clin Endocrinol Metab 90:3550-9 |
| Wang, Christina; Catlin, Don H; Demers, Laurence M et al. (2004) Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metab 89:534-43 |
| Wang, Christina; Catlin, Don H; Starcevic, Borislav et al. (2004) Testosterone metabolic clearance and production rates determined by stable isotope dilution/tandem mass spectrometry in normal men: influence of ethnicity and age. J Clin Endocrinol Metab 89:2936-41 |
| Starcevic, B; DiStefano, E; Wang, C et al. (2003) Liquid chromatography-tandem mass spectrometry assay for human serum testosterone and trideuterated testosterone. J Chromatogr B Analyt Technol Biomed Life Sci 792:197-204 |
