XPD基因单核苷酸多态性与乳腺癌易感性Meta分析

Meta-analysis of the association between XPDgene single nucleotide polymorphisms and breast cancer

目的既往关于核苷酸剪切修复通路中,着色性干皮病基因D(xeroderma pigmentosum group D,XPD)基因单核苷酸多态性Lys751Gln和Arg156Arg与乳腺癌易感性关系研究的结论存在争议。本研究采用Meta分析方法定量评价Lys751Gln和Arg156Arg与乳腺癌易感性关系。方法全面检索CNKI、万方、Pubmed、Cochrane Library和EMBASE数据库中关于Lys751Gln、Arg156Arg与乳腺癌易感性关系的文献,Rev Man 5.0和StataSE 12.0软件进行Meta分析,合并OR值及95%CI绘制森林图。逐一剔除每项研究进行敏感性分析,漏斗图法和Begger’s检验判断发表偏倚,假阳性结果报告率(false positive report probability,FPRP)评价假阳性错误概率。结果共纳入37篇文献,包括17 692例乳腺癌患者和18 325例对照。Lys751Gln位点CC基因型相对于AA基因型是乳腺癌发生的危险因素,OR=1.27,95%CI为1.07~1.50,P=0.01,FPRP值为0.043;显性模型OR=1.13,95%CI为1.02~1.24,P=0.02,FPRP值为0.082;隐性模型OR=1.24,95%CI为1.05~1.46,P=0.01,FPRP值为0.082。亚组分析结果中发现,仅在非亚洲人群中该关联差异有统计学意义,AC相对于AA,OR=1.07,95%CI为1.01~1.13,P=0.01;CC相对于AA,OR=1.30,95%CI为1.08~1.57,P=0.01;显性模型OR=1.17,95%CI为1.04~1.31,P=0.01;隐性模型OR=1.26,95%CI为1.05~1.52,P=0.01。未得到Arg156Arg位点与乳腺癌发生有意义的结果,P>0.05。结论 XPD基因Lys751Gln位点与乳腺癌的发生存在一定的关联,尚未发现Arg156Arg位点与乳腺癌的发病有关。

OBJECTIVE Previous studies on the association between Lys751 Gln and Arg156 Arg and breast cancer susceptibility for Xeroderma pigmentosum group D(XPD)gene SNPS in nucleotide excision repair pathways are controversial.In this paper,meta-analysis was used to quantitatively evaluate the relationship between Lys751 Gln and Arg156 Arg and breast cancer susceptibility.METHODS CNKI,Wanfang database,Pubmed,Cochrane Library and EMBASE were used for literature searching.Rev Man 5.0 and StataSE 12.0 were used to carry out the meta-analysis.Pooled ORs and 95%confidence interval were calculated to form forest plots.Sensitivity analysis by omitting each study one by one were performed;funnel plots and Begger`s test were used to assess the publication bias;the false positive report probability(FPRP)was used to reduce the probability of false-positive findings.RESULTS A total of 37 studies were included with 17,692 cases and 18,325 controls.Compared to AA genotype,Lys751 Gln CC genotype was a risk factor for breast cancer,OR=1.27,95%CI=1.07-1.50,P=0.01,FPRP=0.043.The dominance model OR=1.13,95%CI=1.02-1.24,P=0.02,FPRP=0.082.The recessive model OR=1.24,95%CI=1.05-1.46,P=0.01,FPRP=0.082.Subgroup analysis results showed that the statistical significance only in non-Asian populations,AC versus AA:OR=1.07,95%CI=1.01-1.13,P=0.01.CC Versus AA,OR=1.30,95%CI=1.08-1.57,P=0.01.The dominance model OR=1.17,95%CI=1.04-1.31,P=0.01.The recessive model OR=1.26,95%CI=1.05-1.52,P=0.01.No significant link between Arg156 Arg and breast cancer was found,P>0.05.CONCLUSIONS Lys751 Gln of XPD was associated with breast cancer.While Arg156 Arg has not been found to be associated with breast cancer.