Rare Earth Element Concentrations, Speciation, and Fractionation along Groundwater Flow Paths: The Carrizo Sand (Texas) and Upper Floridan Aquifers

Abstract

Our recent study demonstrated the increased risk of renal cell carcinoma (RCC) associated with high urinary total arsenic levels among people living in a low arsenic exposure area. Genomic instability is important in arsenic carcinogenesis. This study evaluated the relationship between the polymorphisms of p53, p21, and MDM2, which plays a role in gene stability, and the arsenic-related RCC risk. Here, we found that p53 Pro/Pro genotype and MDM2 SNP309 GG genotype significantly increased RCC risk compared to the p53 Arg/Arg genotype and MDM2 SNP309 TT genotype. Subjects with the p53 Arg/Arg genotype had a significantly low percentage of inorganic arsenic, a low percentage of monomethylarsonic acid (MMA), and a high percentage of dimethylarsinic acid (DMA), which indicates efficient arsenic methylation capacity. Subjects with the p53 Arg/Pro+Pro/Pro genotype or MDM2 SNP309 TG+GG genotype, in conjunction with high urinary total arsenic (>15.95μg/g creatinine), had a significantly higher RCC risk than those with the p53 Arg/Arg or MDM2 SNP30 TT genotypes and low urinary total arsenic. Taken together, this is the first study to show that a variant genotype of p53 Arg(72)Pro or MDM2 SNP309 may modify the arsenic-related RCC risk even in a non-obvious arsenic exposure area.