The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area

Chao Yuan Huang, Chien Tien Su, Jan Show Chu, Shu Pin Huang, Yeong Shiau Pu, Hsiu Yuan Yang, Chi Jung Chung, Chia Chang Wu, Yu Mei Hsueh

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)349-355
Number of pages7
JournalToxicology and Applied Pharmacology
Volume257
Issue number3
DOIs
Publication statusPublished - Dec 15 2011

Fingerprint

Arsenic
Polymorphism
Renal Cell Carcinoma
Codon
Cells
Genotype
Cacodylic Acid
Methylation
Genomic Instability
Carcinogenesis
Genes

Keywords

  • Arsenic
  • Arsenic methylation
  • MDM2
  • P53
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area. / Huang, Chao Yuan; Su, Chien Tien; Chu, Jan Show; Huang, Shu Pin; Pu, Yeong Shiau; Yang, Hsiu Yuan; Chung, Chi Jung; Wu, Chia Chang; Hsueh, Yu Mei.

In: Toxicology and Applied Pharmacology, Vol. 257, No. 3, 15.12.2011, p. 349-355.

Research output: Contribution to journalArticle

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