The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area
Journal
Toxicology and Applied Pharmacology
Journal Volume
257
Journal Issue
3
Pages
349-355
Date Issued
2011
Author(s)
Su C.-T.
Chu J.-S.
Huang S.-P.
Yang H.-Y.
Chung C.-J.
Wu C.-C.
Hsueh Y.-M.
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. RCC patients with the p53 Arg/Arg genotype had a signicantly low percentage of inorganic arsenic, a low percentage of monomethylarsonic acid (MMA), and a high percentage of dimethylarsinic acid (DMA), which indicates efcient 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 (?14.02μg/L), had a signicantly higher RCC risk than those with the p53 Arg/Arg or MDM2 SNP309 TT genotypes and low urinary total arsenic. Taken together, this is the first study to show that a variant genotype of p53 Arg 72Pro or MDM2 SNP309 may modify the arsenic-related RCC risk even in a non-obvious arsenic exposure area. ? 2011 Elsevier Inc.
SDGs
Other Subjects
arginine; arsenic; cacodylic acid; guanosine; methanearsonic acid; proline; protein MDM2; protein p21; protein p53; thymidine; MDM2 protein, human; protein MDM2; protein p53; adult; article; cancer patient; cancer risk; controlled study; environmental exposure; female; genetic association; genetic polymorphism; genotype; human; human tissue; kidney carcinoma; major clinical study; male; methylation; single nucleotide polymorphism; urinalysis; case control study; codon; genetic predisposition; genetics; kidney tumor; middle aged; pathology; risk; urine; Arsenic; Carcinoma, Renal Cell; Case-Control Studies; Codon; Environmental Exposure; Female; Genetic Predisposition to Disease; Genotype; Humans; Kidney Neoplasms; Male; Middle Aged; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-mdm2; Risk; Tumor Suppressor Protein p53
Type
journal article