Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Toxicol Appl Pharmacol. 2011 Dec 15;257(3):349-55. doi: 10.1016/j.taap.2011.09.018. Epub 2011 Sep 29.
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 p53Arg/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(72)Pro or MDM2 SNP309 may modify the arsenic-related RCC risk even in a non-obvious arsenic exposure area.
我们最近的研究表明，在低砷暴露地区生活的人群中，尿液总砷水平升高与肾细胞癌（RCC）风险增加有关。基因组不稳定性在砷致癌作用中很重要。本研究评估了在基因稳定性中起作用的 p53、p21 和 MDM2 多态性与砷相关的 RCC 风险之间的关系。在这里，我们发现与 p53 Arg/Arg 基因型和 MDM2 SNP309 TT 基因型相比，p53 Pro/Pro 基因型和 MDM2 SNP309 GG 基因型显著增加了 RCC 风险。p53Arg/Arg 基因型的 RCC 患者无机砷百分比显著降低，单甲基砷酸（MMA）百分比降低，二甲基砷酸（DMA）百分比升高，表明砷甲基化能力较强。p53 Arg/Pro + Pro/Pro 基因型或 MDM2 SNP309 TG+GG 基因型与高尿总砷（≥14.02μg/L）相结合的受试者，其 RCC 风险明显高于 p53 Arg/Arg 或 MDM2 SNP309 TT 基因型和低尿总砷的受试者。综上所述，这是第一项表明 p53 Arg(72)Pro 或 MDM2 SNP309 变异基因型甚至在非明显砷暴露地区也可能改变与砷相关的 RCC 风险的研究。
