Polymorphisms of the DNA polymerase β gene in breast cancer
Polymorphisms of the DNA polymerase β gene in breast cancer
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DOI：
10.1007/s10549-006-9357-y
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发表时间：
2007-06-01
影响因子：
3.8
通讯作者：
Blasiak, Janusz
中科院分区：
文献类型：
--
作者：
Sliwinski, Tomasz;Ziemba, Pawel;Blasiak, Janusz
DNA聚合酶β（Pol β）在碱基切除修复途径中在受损DNA的脱嘌呤/脱嘧啶位点处提供大部分间隙填充合成。已在各种癌中鉴定出编码DNA pol β的基因中的突变。我们进行了一项病例对照研究，以测试pol β基因中两种多态性之间的关联：密码子242处的Pro -> Arg改变（Pro242 Arg多态性）和密码子289处的Lys -> Met改变（Lys 289 Met多态性）与乳腺癌风险和癌症进展之间的关联。采用PCR-RFLP方法对150例乳腺癌患者和150例年龄匹配的无癌妇女（对照组）外周血淋巴细胞DNA进行基因型测定。乳腺癌发生与Lys 289 Met多态性的Met/Met表型[比值比（OR）3.67; 95%置信区间（CI）1.87-7.56]和Pro 242 Lys多态性的Pro/Arg表型之间存在强相关性（OR 1.96; Lys 289 Met的Met/Met表型和Pro/Met表型之间的多态性-多态性相互作用（95%CI 1.15-3.34）被发现。Pro242 Arg变异体的Arg表型增加了乳腺癌的风险（OR 3.05; 95%CI 1.31-7.09）。我们没有观察到研究的多态性和乳腺癌进展之间的任何相关性评估的淋巴结转移，肿瘤大小和布卢姆-理查森分级。结论：Pol β可能在乳腺癌的发生发展中起一定作用，Pol β基因Lys 289 Met多态性可作为乳腺癌独立的早期分子诊断标志物。Pro242 Arg多态性可能通过与Lys 289 Met的相互作用而参与肿瘤的发生，因此可作为一种依赖性的辅助标志物。
DNA polymerase beta (Pol beta) provides most of the gap-filling synthesis at apurinic/apyrimidine sites of damaged DNA in the base excision repair pathway. Mutations in the gene encoding DNA pol beta have been identified in various carcinomas. We performed a case-control study to test the association between two polymorphisms in the pol beta gene: a Pro -> Arg change at codon 242 (the Pro242Arg polymorphism) and a Lys -> Met change at codon 289 (the Lys289Met polymorphism) and breast cancer risk and cancer progression. Genotypes were determined in DNA from peripheral blood lymphocytes of 150 breast cancer patients and 150 cancer-free, age-matched women (controls) by PCR-RFLP. A strong association between breast cancer occurrence and the Met/Met phenotype of the Lys289Met polymorphism [odds ratio (OR) 3.67; 95% confidence interval (CI) 1.87-7.56] and the Pro/Arg phenotype of the Pro242Lys polymorphism (OR 1.96; 95% CI 1.15-3.34) was found. Polymorphism-polymorphism interaction between the Met/Met phenotype of the Lys289Met and the Pro/Arg phenotype of the Pro242Arg variants increased the risk of breast cancer (OR 3.05; 95% CI 1.31-7.09). We did not observe any correlation between studied polymorphisms and breast cancer progression evaluated by node-metastasis, tumor size and Bloom-Richardson grading. In conclusion, Pol beta may play a role in the breast carcinogenesis and the Lys289Met polymorphism of the pol beta gene may be considered as an independent, early, molecular diagnostic marker in breast cancer. The Pro242Arg polymorphism may contribute to the carcinogenesis through the interaction with the Lys289Met and therefore may be regarded as a dependent, auxiliary marker.