Our previous studies have well documented that the poor arsenic methylation capability is associated with an increased risk of urothelial carcinoma either in arseniasis endemic area or in non arsenic exposure area. At recent renal cell carcinoma (RCC) increases gradually, and it has no special risk factors and it do not have typical symptoms not easily to detect. Treatment is not efficient when the late stage of RCC is diagnosed. Therefore, it is very important to explore the risk factors of RCC. However, papers discussed carcinogenic mechanism of RCC is still sparse. Therefore, the specific aims of this project are to explore the association among arsenic methylation capability, arsenic methylation related enzymes genotype, 8-Hydroxydeoxyguanosine (8-OHdG), the polymorphism of insulin receptor substrates enzymes and renin-angiotensin-aldosterone system and RCC. This project is a three-year prospective study. We will use all study subjects recruited previously and they provided informed consents, and carried out questionnaire interview and their biospecimens including plasma, buffy coat, and urine were collected from non arsenic exposure area, and their urinary arsenic species were determined. We will continue to collect 150 RCC patients and 300 controls in next three years. First year we will use 150 RCC patients and 300 healthy controls recruited previously and 50 new RCC patients and new 100 controls to examine the polymorphism of arsenic methylation related enzymes (arsenic methyltransferase; AS3MT、purine nucleoside phosphorylases; PNP、Glutathione-S- transferase Omega; GSTO1and Glutathione-Stransferase Omega; GSTO2) of subjects. In addition, we will examine arsenic methylation capability of new RCC patients and controls. Second year we will continue to recruit new 50 RCC patients and 100 controls to examine the arsenic methylation capability, and arsenic methylation related enzymes genotype of subjects. In addition, we will analyze the polymorphism of insulin receptor substrates enzymes (insulin receptor substrate 1; IRS-1 (Gly972Arg)、insulin receptor substrate 2; IRS-2 (Gly1057Asp) and phosphatidylinositol 3- kinase; PI 3-K (Met326Ile)) and urinary 8-OHdG of all study subjects. Third year we will continue to recruit 50 RCC patients, and 100 controls to assay the arsenic methylation capability, and the polymorphism of arsenic methylation related enzymes and insulin receptor substrates enzymes, and urinary 8-OHdG. We will also analyze the polymorphism of renin-angiotensin-aldosterone system (angiotensinogen; AGT、 angiotensin-converting enzyme; ACE、angiotensin II typeⅠreceptor; AGT1R and CYP11B2) of all study subjects. This study will use external exposure dose, internal dose and susceptibility data to perform molecular epidemiology for examining arsenic methylation capability, 8-OHdG, and polymorphism of RAAS and insulin receptor substrates enzymes on RCC risk. Finally, we will incorporate all external exposure dose, internal dose and susceptibility data to perform statistical analyses. We anticipate setting up and evaluating the arsenic methylation capability, the polymorphism of arsenic methylation related enzymes, insulin receptor substrates enzymes and renin-angiotensin-aldosterone system, and urinary 8-OHdG on RCC risk in non arsenic exposure area. The findings from these three years projects are expected to publish in internationally prestigious journals.
|Effective start/end date||8/1/14 → 7/31/15|
- Arsenic Methylation Capability
- Arsenic Methylation Related Enzymes
- Genetic Polymorphism
- Insulin Receptor Substrates
- Renin-Angiotensin-Aldosterone System
- Renal Cell Carcinoma