He Xiaohong, Ye Feng, Zhang Jing, Cheng Qi, Shen Jiajie, Chen Huaizeng
Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Pathobiology. 2008;75(6):356-63. doi: 10.1159/000164220. Epub 2008 Dec 15.
DNA repair genes play a key role in maintaining genomic stability and integrity. DNA repair gene polymorphisms, such as those of XRCC3 and xeroderma pigmentosum, complementation group D and G (XPD, XPG), contribute to carcinogenesis. In this study, we investigated the correlation between cervical carcinoma risk and XRCC3, XPD, XPG genetic variants.
A case-control study of 400 cases including 200 carcinoma, 200 cervical intraepithelial neoplasia (CIN) and 200 normal women was performed. Four single nucleotide polymorphisms (SNPs) (XRCC3 Thr241Met, XPG His1104Asp, XPD Asp312Asn, and XPD Lys751Gln) were genotyped by mismatch amplification polymerase chain reaction.
Women carrying homozygous Asp1104Asp genotypes had a significantly decreased risk of cervical or cervical squamous cell carcinoma compared to His1104Asp or His1104His genotypes. Similarly, XPD Asn312Asn (AA) reduced the risk of cervical or cervical squamous cell carcinoma. No association of XRCC3 Thr241Met or XPD Lys751Gln and cervical carcinoma was found. None of the 4 SNPs influenced the risk of CIN in our study.
Our results support the hypothesis that genetic variations in DNA repair genes may contribute to an inherited genetic susceptibility to cervical carcinoma.
DNA修复基因在维持基因组稳定性和完整性方面发挥关键作用。DNA修复基因多态性,如X射线修复交叉互补基因3(XRCC3)以及着色性干皮病互补组D和G(XPD、XPG)的多态性,与癌症发生有关。在本研究中,我们调查了宫颈癌风险与XRCC3、XPD、XPG基因变异之间的相关性。
进行了一项病例对照研究,包括400例受试者,其中200例为宫颈癌患者,200例为宫颈上皮内瘤变(CIN)患者,200例为正常女性。通过错配扩增聚合酶链反应对四个单核苷酸多态性(SNP)(XRCC3第241位苏氨酸突变为甲硫氨酸、XPG第1104位组氨酸突变为天冬氨酸、XPD第312位天冬氨酸突变为天冬酰胺以及XPD第751位赖氨酸突变为谷氨酰胺)进行基因分型。
与携带第1104位组氨酸突变为天冬氨酸或第1104位组氨酸纯合子基因型的女性相比,携带第1104位天冬氨酸纯合子基因型的女性患宫颈癌或宫颈鳞状细胞癌的风险显著降低。同样,XPD第312位天冬酰胺纯合子(AA)降低了患宫颈癌或宫颈鳞状细胞癌的风险。未发现XRCC3第241位苏氨酸突变为甲硫氨酸或XPD第751位赖氨酸突变为谷氨酰胺与宫颈癌有关。在我们的研究中,这4个SNP均未影响CIN的风险。
我们的结果支持以下假设,即DNA修复基因的遗传变异可能导致宫颈癌的遗传易感性。