Urinary Total Arsenic Levels, Arsenic Methylation Capacity, Plasma Selenium Concentrations and Genetic Polymorphisms of Glutathione Peroxidase and Selenoprotein and Prostate Cancer

Our previous studies have well documented that the inefficient arsenic methylation capacity was associated with an increased risk of urothelial carcinoma either in arseniasis endemic area or in non-obvious arsenic exposure area. We also found that urinary total arsenic level was significantly associated with the odds ratio of chronic kidney disease and renal cell carcinoma in a dose-response relationship. Incidence and mortality of prostate cancer increased year by year, raises an important public health issue in Taiwan. Therefore, it is very important to explore the etiology of prostate cancer. Previous epidemiologic studies from Taiwan populations chronically exposed to high arsenic levels in drinking water showed a significant mortality of prostate cancer, with a dose-response relationship. Previous studies used arsenic concentrations in drinking water as an arsenic exposure index mostly; however, the investigation is needed to use internal dose index such as urinary total arsenic level as an arsenic exposure index to determine whether urinary total arsenic level and arsenic methylation capacity are associated with prostate cancer. Arsenic and selenium have marked differences in their biological effects. Selenium is an essential trace element necessary for antioxidant enzyme activity. Plasma selenium concentrations can be used as an index of selenium intake. Selenium has a protective effect against arsenic induced oxidative damage. Many antioxidant enzymes were regulated by selenium, which including glutathione peroxidase (GPX) and selenoprotein P. The association between the polymorphisms of GPX (GPX1 rs1050450, GPX2 rs4902346, GPX3 rs4958872 and GPX4 rs713041and rs2075710) and selenoprotein P (SEPP1 rs3797310 and SEP15 rs5859) and prostate cancer was reported inconsistently from previous studies. Therefore, the specific aims of this project are to explore the association among urinary total arsenic levels, arsenic methylation capacity, plasma selenium concentrations, and gene polymorphism of GPX (GPX1 rs1050450, GPX2 rs4902346, GPX3 rs4958872 and GPX4 rs713041and rs2075710) and selenoprotein P (SEPP1 rs3797310 and SEP15 rs5859) and prostate cancer. In addition, we will explore the interaction of urinary total arsenic levels, arsenic methylation capacity, plasma selenium concentrations, and gene polymorphism of GPX and selenoprotein P on prostate cancer after adjustment for other risk factors. This project is a one-year prospective study. We will use 300 prostate cancer patients and 300 healthy controls recruited previously in our pilot study from the National Taiwan University Hospital and the Taipei Municipal Wan Fang Hospital. This study was approved by the Research Ethics Committee of National Taiwan University Hospital and Taipei Medical University, and all participants provided their written informed consent before questionnaire interviews and biological specimen collection including plasma, buffy coat, and urine. The urinary arsenic species levels and plasma selenium concentration of 300 prostate cancer patients and 300 healthy controls were measured already, and the manuscript about the association between urinary total arsenic levels, arsenic methylation capacity and plasma selenium levels and prostate cancer was submitted. We will continue to recruit 75 prostate cancer patients and 75 healthy controls respectively in next year. We will examine new study subjects’ urinary arsenic species levels using established methods-high performance liquid chromatograph linked to hydride generator and atomic absorption spectrophotometry, and their plasma selenium concentrations were measured by established methods-inductively coupled plasma mass. We also examine the gene polymorphisms of GPX (GPX1 rs1050450, G'PX2 rs4902346, GPX3 rs4958872 and GPX4 rs713041and rs2075710) and selenoprotein P (SEPP1 rs3797310 and SEP15 rs5859) using polymerase chain reaction-restriction fragment length polymorphism method for all study subjects in this project. This study will use external exposure dose, internal dose and susceptibility genes to perform molecular epidemiology of prostate cancer for examining the association among urinary total arsenic levels, arsenic methylation capacity, plasma selenium concentrations, and gene polymorphisms of GPX (GPX1 rs1050450, Gp^2 rs4902346, GPX3 rs4958872 and GPX4 rs713041and rs2075710) and selenoprotein P (SEPP1 rs3797310 and SEP15 rs5859) and prostate cancer after adjustment for other risk factors. We will incorporate all external exposure dose, internal dose and susceptibility genes to perform statistical analyses. We anticipate setting up and evaluating the association between urinary total arsenic levels, arsenic methylation capacity, plasma selenium concentrations, and gene polymorphisms of GPX (GPX1 rs1050450, GPX2 rs4902346, GPX3 rs4958872 and GPX4 rs713041and rs2075710) and selenoprotein P (SEPP1 rs3797310 and SEP15 rs5859) and prostate cancer. We expect to understand a part of mechanisms on prostate cancer. The findings from this project are expected to publish in internationally prestigious journals.