Hirata Hiroshi, Hinoda Yuji, Kawamoto Ken, Kikuno Nobuyuki, Suehiro Yutaka, Okayama Naoko, Tanaka Yuichiro, Dahiya Rajvir
Department of Urology, Veterans Affairs Medical Center and University of California at San Francisco, San Francisco, California 94121, USA.
J Urol. 2008 May;179(5):2020-4. doi: 10.1016/j.juro.2008.01.009. Epub 2008 Mar 20.
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.
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.
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).
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.
错配修复系统是一种DNA修复机制，可纠正DNA复制错误期间的错配碱基。缺乏错配修复蛋白的癌细胞突变率增加10²至10³倍。错配修复基因的单核苷酸多态性已被证明会导致DNA修复活性降低。我们假设错配修复基因多态性可能是前列腺癌的危险因素，并且p53 Pro/Pro基因型携带者可能会影响MSH3和MSH6多态性。
通过单链构象多态性和聚合酶链反应-限制性片段长度多态性分析110例前列腺癌患者和110例健康对照的DNA样本，以确定2个错配修复基因（MSH3和MSH6）和p53密码子72上5个多态性位点的基因型频率。应用卡方检验比较患者和对照之间的基因型频率。
与对照相比，患者中MSH3 Pro222Pro的G/A+A/A基因型显著增加（OR 1.87，95%CI 1.0-3.5）。患者中MSH3外显子23 Thr1036Ala的A/G + G/G基因型频率也有增加趋势（OR 1.57，95%CI 0.92-2.72）。在p53密码子72 Arg/Pro + Pro/Pro携带者中，与对照相比，患者中MSH3外显子23的AG + GG基因型频率显著增加（OR 2.1，95%CI 1.05-4.34）。
据我们所知，这是关于前列腺癌中MSH3基因多态性关联的首次报道。这些结果表明MSH3多态性可能是前列腺癌的危险因素。
