Common Polymorphisms in the XPD and hOGG1 Genes Are Not Associated with the Risk of Colorectal Cancer in a Polish Population
Common Polymorphisms in the XPD and hOGG1 Genes Are Not Associated with the Risk of Colorectal Cancer in a Polish Population
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DOI：
10.1620/tjem.218.185
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发表时间：
2009-07-01
影响因子：
2.2
通讯作者：
Blasiak, Janusz
中科院分区：
文献类型：
--
作者：
Sliwinski, Tomasz;Krupa, Renata;Blasiak, Janusz
DNA修复基因的突变可能导致癌症风险增加，包括结直肠癌。着色性干皮病D组（XPD）蛋白和8-氧代鸟嘌呤糖基化酶1（hOGG 1）的人类同系物分别参与核苷酸切除修复和碱基切除修复。XPD和hOGG 1基因是高度多态性的，它们的一些多态性与几种类型的癌症相关。然而，它们的多态性与结直肠癌的风险之间的关系存在争议。因此，在本研究中，我们在波兰人群中寻找结直肠癌与两种常见多态性之间的关联：XPD基因中的A -> C颠换，其在密码子751处产生Lys到Gln的取代（Lys 751 Gln多态性; rs 28365048）和hOGG 1基因中的C -> G颠换导致密码子326处的Ser至Cys改变（Ser 326 Cys多态性; rs 1052133）。通过PCR和限制性片段长度多态性分析，确定100例结直肠癌患者和100例年龄、性别和种族匹配的无癌对照的外周血淋巴细胞的基因型。我们没有发现每个多态性与结直肠癌发生之间的统计学显著关联，也没有观察到每个多态性与结直肠癌进展（通过淋巴结转移、肿瘤大小和杜克分期评估）之间的任何关系。此外，这两个多态性的组合基因型与结直肠癌之间没有相关性。因此，在波兰人群中，XPD基因的Lys 751 Gln多态性和hOGG 1基因的Ser 326 Cys多态性与结直肠癌无关。
Mutations in the DNA repair genes may contribute to the increased risk of cancer, including colorectal cancer. Xeroderma pigmentosum group D (XPD) protein and human homolog of the 8-oxoguanine glycosylase 1 (hOGG1) are involved in nucleotide excision repair and base excision repair, respectively. The XPD and the hOGG1 genes are highly polymorphic, and some of their polymorphisms are associated with several types of cancers. However, there is controversy as to the relationship between their polymorphisms and the risk of colorectal cancer. In the present study, we therefore searched for the association in a Polish population between colorectal cancer and two common polymorphisms: an A -> C transversion in the XPD gene that produces a Lys-to-Gln substitution at codon 751 (the Lys751Gln polymorphism; rs28365048) and a C -> G transversion in the hOGG1 gene resulting in a Ser-to-Cys change at codon 326 (the Ser326Cys polymorphism; rs1052133). Genotypes were determined using peripheral blood lymphocytes of 100 colorectal cancer patients and 100 age-, sex- and ethnicity-matched cancer-free controls by PCR and restriction fragment-length polymorphism analysis. We did not find statistically significant association between each polymorphism and the occurrence of colorectal cancer, and did not observe any relationship between each polymorphism and colorectal cancer progression assessed by node metastasis, tumor size and Duke's stage. Moreover, there was no correlation between combined genotypes of the two polymorphisms and colorectal cancer. Therefore, the Lys751 Gln polymorphism of the XPD gene and the Ser326Cys polymorphism of the hOGG1 gene are not associated with colorectal cancer in a Polish population.