Dai Zhi-Jun, Liu Xing-Han, Ma Yun-Feng, Kang Hua-Feng, Jin Tian-Bo, Dai Zhi-Ming, Guan Hai-Tao, Wang Meng, Liu Kang, Dai Cong, Yang Xue-Wen, Wang Xi-Jing
From the Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University (Z-JD, X-HL, X-JW, H-FK, H-TG, MW, KL, CD, X-WY, X-JW); Department of Immunology and Pathogenic Biology, Xi'an Jiaotong University (Y-FM); National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University (T-BJ); and Department of Anesthesia, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China (Z-MD).
Medicine (Baltimore). 2016 Jan;95(2):e2466. doi: 10.1097/MD.0000000000002466.
DNA polymerases are responsible for ensuring stability of the genome and avoiding genotoxicity caused by a variety of factors during DNA replication. Consequently, these proteins have been associated with an increased cancer risk. DNA polymerase kappa (POLK) is a specialized DNA polymerase involved in translesion DNA synthesis (TLS) that allows DNA synthesis over the damaged DNA. Recently, some studies investigated relationships between POLK polymorphisms and cancer risk, but the role of POLK genetic variants in breast cancer (BC) remains to be defined. In this study, we aimed to evaluate the effects of POLK polymorphisms on BC risk.We used the Sequenom MassARRAY method to genotype 3 single nucleotide polymorphisms (SNPs) in POLK (rs3213801, rs10077427, and rs5744533), in order to determine the genotypes of 560 BC patients and 583 controls. The association of genotypes and BC was assessed by computing the odds ratio (OR) and 95% confidence intervals (95% CIs) from logistic regression analyses.We found a statistically significant difference between patient and control groups in the POLK rs10077427 genotypic groups, excluding the recessive model. A positive correlation was also found between positive progesterone receptor (PR) status, higher Ki67 index, and rs10077427 polymorphism. For rs5744533 polymorphism, the codominant, dominant, and allele models frequencies were significantly higher in BC patients compared to healthy controls. Furthermore, our results indicated that rs5744533 SNP has a protective role in the postmenopausal women. However, we failed to find any associations between rs3213801 polymorphism and susceptibility to BC.Our results indicate that POLK polymorphisms may influence the risk of developing BC, and, because of this, may serve as a prognostic biomarker among Chinese women.
DNA聚合酶负责确保基因组的稳定性，并避免DNA复制过程中由多种因素引起的基因毒性。因此，这些蛋白质与癌症风险增加有关。DNA聚合酶κ（POLK）是一种参与跨损伤DNA合成（TLS）的特殊DNA聚合酶，它允许在受损DNA上进行DNA合成。最近，一些研究调查了POLK多态性与癌症风险之间的关系，但POLK基因变异在乳腺癌（BC）中的作用仍有待确定。在本研究中，我们旨在评估POLK多态性对BC风险的影响。我们使用Sequenom MassARRAY方法对POLK中的3个单核苷酸多态性（SNP）（rs3213801、rs10077427和rs5744533）进行基因分型，以确定560例BC患者和583例对照的基因型。通过逻辑回归分析计算优势比（OR）和95%置信区间（95%CI）来评估基因型与BC的关联。我们发现，在POLK rs10077427基因型组中，患者组和对照组之间存在统计学上的显著差异，不包括隐性模型。在孕激素受体（PR）阳性状态、较高的Ki67指数与rs10077427多态性之间也发现了正相关。对于rs5744533多态性，与健康对照相比，BC患者的共显性、显性和等位基因模型频率显著更高。此外，我们的结果表明，rs5744533 SNP对绝经后女性具有保护作用。然而，我们未发现rs3213801多态性与BC易感性之间存在任何关联。我们的结果表明，POLK多态性可能影响BC的发生风险，因此，在中国女性中可能作为一种预后生物标志物。
