The role of molecular genetics in chemoprevention studies of prostate cancer.
Research into the molecular genetics of prostate cancer to date has largely focused on the possible existence of one or several single-locus high-penetrance susceptibility genes and several candidate regions have been Identified, but confirmatory studies of these regions have been inconclusive. Increasingly, attention has turned to identification of candidate genes which may increase prostate cancer risk because their products play an important role in possible etiological pathways for prostate cancer. Of various such pathways which have been suggested for prostate cancer, the best studied in terms of molecular genetics is the androgen signalling pathway. Two genes in this pathway, the androgen receptor (AR) gene and the steroid 5-alpha reductase type II (SRD5A2) gene, have been under particular scrutiny and polymorphic markers in each of these genes that reproducibly predict prostate cancer risk have been identified. Such studies may have important implications for prostate cancer chemoprevention trials. As etiological pathways become better understood at the molecular level, piecing together multiple genetic variants in a pathway will allow identification of high-risk individuals and potential targets for chemopreventive interventions. Moreover, understanding the role of these genes in prostate cancer etiology may help in defining heterogeneity in response to such interventions. Finally, these genes or their products may themselves be legitimate targets for building a chemoprevention strategy.
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D000728:Androgens / Q000235:genetics / Q000378:metabolism*; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D004341:Drug Evaluation / Q000379:methods; D005820:Genetic Testing; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000517:prevention & control; D015398:Signal Transduction / Q000235:genetics; D014810:Vitamin E / Q000235:genetics / Q000378:metabolism*
D000728:Androgens; D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D014810:Vitamin E