Abstract A7: Differential glucose metabolites in prostate cancer aggressivity by ethnicity

The observation that chromosome 8q24 has multiple prostate cancer susceptibility loci that independently affect inherited risk for disease aggressivity suggested an underlying genetic basis for the observed disparities in prostate cancer risks between African Americans and Caucasians. We reasoned that genetic differences in glucose metabolism leading to subtle quantitative alterations in levels of glucose metabolites synergizes with genetic defects to selectively and adversely modulate disease onset, disease progression and disease outcome in African Americans compared to Caucasians. Consistent with this notion, we hypothesized that distinct and quantifiable differences in glucose metabolites underlie the prevalence of aggressive prostate cancer in African Americans relative to Caucasians. Towards this end, we have used ¹³C tracer-based methodology and quantitative ¹H NMR and ¹H-¹H TOCSY to perform comparative metabolomic analysis of age- and stage-matched representative cell lines derived from American American (PCa2b) and Caucasian (PC3). The data shows substantial differences in rates of glucose utilization and in rates of lactate secretion. Additional quantitative alterations were observed in key glucose metabolites. Differences in the genetic regulation of glucose metabolism and of its metabolites provide additional alternative explanation for the increased incidence and the poorer prognosis of prostate cancer in African-Americans compared to Caucasians.