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

doi:10.1016/j.taap.2011.09.018

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 journal › Article › peer-review

23 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 language	English
Pages (from-to)	349-355
Number of pages	7
Journal	Toxicology and Applied Pharmacology
Volume	257
Issue number	3
DOIs	https://doi.org/10.1016/j.taap.2011.09.018
Publication status	Published - Dec 15 2011

Keywords

Arsenic
Arsenic methylation
MDM2
P53
Renal cell carcinoma

ASJC Scopus subject areas

Toxicology
Pharmacology

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10.1016/j.taap.2011.09.018

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

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.",

keywords = "Arsenic, Arsenic methylation, MDM2, P53, Renal cell carcinoma",

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

note = "Funding Information: The study was supported by grants from the National Science Council of the ROC ( NSC 86-2314-B-038-038, NSC 87-2314-B-038-029, NSC-88-2314-B-038-112, NSC-89-2314-B038-049, SC-89-2320-B038-013, NSC-90-2320-B-038-021, NSC-91-3112-B-038-0019, NSC-92-3112-B-038-001, NSC-93-3112-B-038-001, NSC-94-2314-B-038-023, NSC-95-2314-B-038-007, NSC-96-2314-B038-003, NSC-97-2314-B-038-015-MY3 (1–3), NSC-97-2314-B-038-015-MY3 (2–3), NSC-97-2314-B-038-015-MY3 (3–3) ), and from the Department of Health, Executive Yuan of the ROC ( DOH99-TD-C-111-001, DOH100-TD-C-111-001 ).",

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T1 - The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area

AU - Huang, Chao Yuan

AU - Su, Chien Tien

AU - Chu, Jan Show

AU - Huang, Shu Pin

AU - Pu, Yeong Shiau

AU - Yang, Hsiu Yuan

AU - Chung, Chi Jung

AU - Wu, Chia Chang

AU - Hsueh, Yu Mei

N1 - Funding Information: The study was supported by grants from the National Science Council of the ROC ( NSC 86-2314-B-038-038, NSC 87-2314-B-038-029, NSC-88-2314-B-038-112, NSC-89-2314-B038-049, SC-89-2320-B038-013, NSC-90-2320-B-038-021, NSC-91-3112-B-038-0019, NSC-92-3112-B-038-001, NSC-93-3112-B-038-001, NSC-94-2314-B-038-023, NSC-95-2314-B-038-007, NSC-96-2314-B038-003, NSC-97-2314-B-038-015-MY3 (1–3), NSC-97-2314-B-038-015-MY3 (2–3), NSC-97-2314-B-038-015-MY3 (3–3) ), and from the Department of Health, Executive Yuan of the ROC ( DOH99-TD-C-111-001, DOH100-TD-C-111-001 ).

PY - 2011/12/15

Y1 - 2011/12/15

N2 - 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.

AB - 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.

KW - Arsenic

KW - Arsenic methylation

KW - MDM2

KW - P53

KW - Renal cell carcinoma

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

Abstract

Keywords

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