DNA修复基因XPD、XPA单核苷酸多态性与乳腺癌发病风险的相关性研究

Investigations on the association of single nucleotide polymorphisms of DNA repair XPD,XPA genes with the risk of breast cancer

目的探讨人类着色性干皮病基因D（XPD）的rs238406,rs13181,rs3810366,rs1799793,rs50872及着色性干皮病基因A（XPA）的rs1800975单核苷酸多态性与南京地区女性乳腺癌发病风险、病理特征与乳腺癌相关激素受体水平的相关性。方法采用病例-对照研究,选取298例女性乳腺癌患者作为病例组,298例健康女性作为对照组,用Sequenom Mass Array技术检测6个多态性位点的基因型,Logistic回归模型分析不同基因型与乳腺癌发生、病理特征和相关激素受体水平包括雌激素受体（ER）、孕激素受体（PR）及原癌基因人类表皮生长因子受体2（HER2或Cer B-2）的关系。结果 rs3810366（χ2=14.993,P=0.001）、rs1800975（χ2=8.336,P=0.015）、rs50872（χ2=8.735,P=0.013）位点的各基因型在两组中分布差异有统计学意义。rs3810366 CG基因型（OR=0.54,95%CI：0.37～0.78）在乳腺癌组中的频率（31.54%）低于对照组（46.98%）,GG/CG基因型发生乳腺癌的风险是健康人的0.71倍（OR=0.71,95%CI：0.51～1.00）。rs1800975位点的AG（OR=0.58,95%CI：0.39～0.85）、AA（OR=0.65,95%CI：0.42～0.90）、AA/AG（OR=0.60,95%CI：0.43～0.86）基因型与乳腺癌的发病风险均呈现负相关（OR〈1）;rs50872 CT（OR=1.64,95%CI：1.16～2.32）及TT/CT（OR=1.66,95%CI：1.18～2.30）是乳腺癌的风险因素。ER及Cer B-2水平可影响rs3810366基因位点在病例组与对照组中分布（P〈0.01）。PR与Cer B-2水平影响rs1800975基因位点在两组中的分布（P〈0.05）。对rs50872位点进行分析,在ER、PR及Cer B-2水平正常时,基因型在病例组与对照组中分布差异有统计学意义（P〈0.01）。结论 XPD基因的rs3810366、rs1800975及rs50872位点的单核苷酸多态性与乳腺癌的发生风险具有相关性。对于不同基因位点,ER、PR及Cer B-2的水平与乳腺癌的发生、发展有关。

Objective To investigate the associations of single nucleotide polymorphisms（ SNP） of rs238406,rs13181,rs3810366,rs1799793 and rs50872 in xeroderma pigmentosum group D（ XPD） gene and rs1800975 in xeroderma pigmentosum Group A（ XPA）gene with the risk,pathologic characteristics and related hormone receptor levels of female breast cancer in Nanjing region. Methods A total of 298 female patients with breast cancer and 298 healthy female controls were enrolled in this case-control study. The genotypes of 6 SNPs were determined by the Sequenom Mass Array,and the associations of different genotypes with the development,pathologic characteristics and related hormone receptor levels [including estrogen receptor（ ER）,progesterone receptor（ PR） and human epidermal growth factor receptor-2（ HER2,Cer B-2） ] of breast cancer were analyzed by logistic regression. Results There were significant differences in the frequency of rs3810366（ χ2= 14. 993,P = 0. 001）,rs1800975（ χ2= 8. 336,P = 0. 015） and rs50872（ χ2= 8. 735,P = 0. 013） genotypes between the case and control groups. For rs3810366,the frequency of CG genotype in the case group（ 31. 54%） was significantly lower than that in the control group（ 46. 98%）（ OR = 0. 54,95% CI： 0. 37-0. 78）,and the frequency of GG / CG genotype in the case group was 0. 71 times of that in the control（ OR = 0. 71,95% CI： 0. 51-1. 00）. For rs1800975,the frequencies of AG（ OR = 0. 58,95% CI： 0. 39-0. 85）,AA（ OR = 0. 65,95% CI： 0. 42-0. 90） and AA / AG（ OR = 0. 60,95% CI：0. 43-0. 86） were negatively related to the risk of breast cancer（ OR〈1）. However,for rs50872,the frequencies of CT（ OR = 1. 64,95% CI： 1. 16-2. 32） and TT / CT（ OR = 1. 65,95% CI： 1. 18-2. 30） genotypes were the risk factors of breast cancer. ER and Cer B-2 levels might influence on the distribution of rs3810366 gene locus in the case and control groups（ P〈0.01）. PR and Cer B-2 levels might influence on the distribution of rs1800975 gene locus in the case and control groups（ P〈0.05）. When the ER,PR and Cer B-2 levels were normal,there was significant difference in the distribution of rs50872 genotype between the case and control groups（ P〈0.01）. Conclusion The SNPs of rs3810366,rs1800975 and rs50872 in XPD gene were associated with the risk of breast cancer.Moreover,based on different gene loci,the levels of ER,PR and Cer B-2 were related to the occurrence and development of breast cancer.