Mismatch repair gene MSH3 polymorphism is associated with the risk of sporadic prostate cancer
Mismatch repair gene MSH3 polymorphism is associated with the risk of sporadic prostate cancer
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DOI：
10.1016/j.juro.2008.01.009
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发表时间：
2008-05-01
影响因子：
6.6
通讯作者：
Dahiya, Rajvir
中科院分区：
文献类型：
--
作者：
Hirata, Hiroshi;Hinoda, Yuji;Dahiya, Rajvir
目的：错配修复系统是在DNA复制错误过程中纠正错配碱基的DNA修复机制。缺乏MMR蛋白的癌细胞的突变率增加了10(2)到10(3)倍。错配修复基因的单核苷酸多态可导致DNA修复活性下降。材料与方法：采用单链构象多态和聚合酶链式反应-限制性片段长度多态方法对110例前列腺癌患者和110例健康对照的DNA样本进行分析，检测MMR基因(MSH3和MSH6)和P53密码子72上5个多态位点的基因频率。结果：MSH3Pro222Pro的G/A+A/A等位基因频率显著高于对照组(OR1.87，95%CI 1.0~3.5)。MSH3外显子23 Thr1036Ala的A/G+G/G等位基因频率也有升高趋势(OR1.57，95%CI 0.92~2.72)。在P53密码子72 Arg/Pro+Pro/Pro携带者中，MSH3外显子23的AG+GG基因型频率显著高于对照组(OR2.1，95%CI 1.05~4.34)。结论：MSH3基因多态性与前列腺癌的关联尚属首次报道。这些结果提示，MSH3基因多态性可能是前列腺癌的危险因素。
Purpose: The mismatch repair system is a DNA repair mechanism that corrects mispaired bases during DNA replication errors. Cancer cells deficient in MMR proteins have a 10(2) to 10(3)-fold increase in the mutation rate. Single nucleotide polymorphisms of mismatch repair genes have been shown to cause a decrease in DNA repair activity. We hypothesized that mismatch repair gene polymorphism could be a risk factor for prostate cancer and p53 Pro/Pro genotype carriers could influence MSH3 and MSH6 polymorphisms.Materials and Methods: DNA samples from 110 patients with prostate cancer and 110 healthy controls were analyzed by single strand conformational polymorphism and polymerase chain reaction-restriction fragment length polymorphism to determine the genotypic frequency of 5 polymorphic loci on 2 MMR genes (MSH3 and MSH6) and p53 codon72. The chi-square test was applied to compare genotype frequency between patients and controls.Results: A significant increase in the G/A+A/A genotype of MSH3 Pro222Pro was observed in patients compared to controls (OR 1.87, 95% CI 1.0-3.5). The frequency of A/G + G/G genotypes of MSH3 exon23 Thr1036Ala also tended to increase in patients (OR 1.57, 95% CI 0.92-2.72). In p53 codon72 Arg/Pro + Pro/Pro carriers the frequency of the AG + GG genotype of MSH3 exon23 was significantly increased in patients compared to controls (OR 2.1, 95% CI 1.05-4.34).Conclusions: To our knowledge this is the first report of the association of MSH3 gene polymorphisms in prostate cancer. These results suggest that the MSH3 polymorphism may be a risk factor for prostate cancer.