Dietary Carcinogens and DNA Adducts in Prostate Cancer

Abstract

Prostate cancer (PC) is the most commonly diagnosed non-cutaneous cancer and the second leading cause of cancer-related to death in men. The major risk factors for PC are age, family history, and African American ethnicity. Epidemiological studies have reported large geographical variations in PC incidence and mortality, and thus lifestyle and dietary factors influence PC risk. High fat diet, dairy products, alcohol and red meats, are considered as risk factors for PC. This book chapter provides a comprehensive, literature-based review on dietary factors and their molecular mechanisms of prostate carcinogenesis. A large portion of our knowledge is based on epidemiological studies where dietary factors such as cancer promoting agents, including high-fat, dairy products, alcohol, and cancer-initiating genotoxicants formed in cooked meats have been evaluated for PC risk. However, the precise mechanisms in the etiology of PC development remain uncertain. Additional animal and human cell-based studies are required to further our understandings of risk factors involved in PC etiology. Specific biomarkers of chemical exposures and DNA damage in the prostate can provide evidence of cancer-causing agents in the prostate. Collectively, these studies can improve public health research, nutritional education and chemoprevention strategies.

Figure 1:

Effect of Arachidonic acid (AA) and its metabolite prostaglandin E2 (PGE2) on cell signaling in human prostate cells

Figure 2:

Effect of pro-inflammatory cytokines such as IL-6 and IL-1 on the activation and the cross talk of STAT-3 and NF-κB pathways

Figure 3:

Insulin/IGF signaling in prostate carcinogenesis.

Figure 4:

Chemical structures of prevalent HAAs in cooked meat.

Figure 5:

Representative chromatograms at the MS² scan stage of human prostate samples that were negative and positive for dG-C8-PhIP.

Figure 6:

Metabolic activation of PhIP and dG-C8-PhIP formation in human prostate.