Ethnic Pharmacogenomic Differences in the Management of Asian Patients with Metastatic Prostate Cancer

Progression to metastatic disease occurs in about half of all men who develop prostate cancer (PC), one of the most common cancers in men worldwide. Androgen deprivation therapy has been the mainstay therapy for patients with metastatic PC (mPC) since the 1940s. In the last decade, there has been unprecedented advancement in systemic therapies, e.g., taxane, androgen-signalling pathway inhibitors, and biomarker-driven targeted therapies for various stages of disease, resulting in overall survival improvement. Adding to ongoing controversies over how best to treat these patients is the recognition that ethnicity may influence prognosis and outcomes. This review discusses recent evidence for the impacts of Asian ethnicity specifically, which includes environmental, sociocultural, and genetic factors, on the approach to pharmacological management of mPC. Clear inter-ethnic differences in drug tolerability, serious adverse events (AEs), and genetic heterogeneity must all be considered when dosing and scheduling for treatment, as well as designing future precision studies in PC.

Germline genetic variation in prostate susceptibility does not predict outcomes in the chemoprevention trials PCPT and SELECT

Background The development of prostate cancer can be influenced by genetic and environmental factors. Numerous germline SNPs influence prostate cancer susceptibility. The functional pathways in which these SNPs increase prostate cancer susceptibility are unknown. Finasteride is currently not being used routinely as a chemoprevention agent but the long term outcomes of the PCPT trial are awaited. The outcomes of the SELECT trial have not recommended the use of chemoprevention in preventing prostate cancer. This study investigated whether germline risk SNPs could be used to predict outcomes in the PCPT and SELECT trial. Methods Genotyping was performed in European men entered into the PCPT trial (n = 2434) and SELECT (n = 4885). Next generation genotyping was performed using Affymetrix® Eureka™ Genotyping protocols. Logistic regression models were used to test the association of risk scores and the outcomes in the PCPT and SELECT trials. Results Of the 100 SNPs, 98 designed successfully and genotyping was validated for samples genotyped on other platforms. A number of SNPs predicted for aggressive disease in both trials. Men with a higher polygenic score are more likely to develop prostate cancer in both trials, but the score did not predict for other outcomes in the trial. Conclusion Men with a higher polygenic risk score are more likely to develop prostate cancer. There were no interactions of these germline risk SNPs and the chemoprevention agents in the SELECT and PCPT trials.

The burden of prostate cancer in Canada

The clinical and economic burden of prostate cancer in Canada is substantial,and is rising. Studies indicate that 1 in 7 men will develop prostate cancer duringtheir lifetime, and another 1 in 27 will die because of it. It is estimated that4300 Canadian men will die of prostate cancer in 2008. Age, family history, raceand diet are all risks associated with the development of prostate cancer. A diagnosisof cancer carries a significant burden and like other cancers is a cause ofsignificant anxiety and depression. Uncertainty regarding the value of screeningfor prostate cancer has been, and continues to be, a challenge for primarycare physicians and urologists.