Polymorphism of XRCC1 (at codon 399) and susceptibility to breast cancer, a meta-analysis of the literatures
Polymorphism of XRCC1 (at codon 399) and susceptibility to breast cancer, a meta-analysis of the literatures
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DOI：
10.1007/s10549-008-0051-0
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发表时间：
2009-05-01
影响因子：
3.8
通讯作者：
Ansari-Lari, Maryam
中科院分区：
文献类型：
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作者：
Saadat, Mostafa;Ansari-Lari, Maryam
X射线修复交叉互补组1（XRCC 1）蛋白在碱基切除修复中起重要作用。已经描述了XRCC 1基因中的几种多态性，包括Arg 399 Gln。以前的研究调查Arg 399 Gln XRCC 1基因多态性与乳腺癌风险之间的关联，结果不一致。本研究采用Meta分析的方法，探讨XRCC 1基因（外显子10，Arg 399 Gln）中常见的遗传变异与乳腺癌风险之间的关系。我们确定了36项与XRCC 1 Arg 399 Gln多态性和乳腺癌风险相关的合格研究。这些研究包括43，716例受试者（20，837例患者和22，879例对照）。我们首先估计了Arg/Gln和Gln/Gln基因型与野生型Arg/Arg纯合子相比的风险，然后评估了Gln/Gln与（Arg/Gln+Arg/Arg）和（Gln/Gln +Arg/Gln）与Arg/Arg的风险，分别假设399 Gln等位基因变异的隐性和显性效应。研究之间存在显著异质性。总体OR值显示乳腺癌风险与XRCC 1基因型无关。当研究分为亚洲和西方国家时，研究之间的异质性显著降低。在亚洲国家的研究中，XRCC 1基因多态性与乳腺癌风险之间存在显著相关性。在亚洲国家，Arg/Gln与Arg/Arg（OR = 0.98，95% CI：0.88-1.10）和Gln/Gln+Arg/Gln与Arg/Arg（OR = 1.05，95% CI：0.95-1.18）与乳腺癌风险增加无关。Gln/Gln与Arg/Arg（OR = 1.46，95%CI：1.19-1.79）和Gln/Gln与Arg/Gln+Arg/Arg（OR = 1.49，95%CI：1.22-1.81）相比，均增加了危险性。因此，399 Gln等位基因可能作为一个隐性等位基因与乳腺癌的风险。
The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair. Several polymorphisms in the XRCC1 gene have been described, including Arg399Gln. Previous studies investigating the association between genetic polymorphism of Arg399Gln XRCC1 and risk of breast cancer have provided inconsistent results. A meta-analysis was conducted to investigate the association between common genetic variant in the XRCC1 gene (exon 10, Arg399Gln) with breast cancer risk. We identified 36 eligible studies, in relation to the Arg399Gln polymorphism of XRCC1 and risk of breast cancer. These studies comprised of 43,716 subjects (20,837 patients and 22,879 controls). We first estimated the risk of the genotypes Arg/Gln and Gln/Gln compared with the wild-type Arg/Arg homozygote, and then evaluated the risk of Gln/Gln versus (Arg/Gln+Arg/Arg) and (Gln/Gln+Arg/Gln) versus Arg/Arg, which assumed recessive and dominant effects, respectively, of the variant 399Gln allele. There was significant heterogeneity between studies. The overall ORs showed that the breast cancer risk were not associated with the XRCC1 genotypes. The heterogeneity between studies decreased dramatically when studies stratified into Asian and Western countries. There was significant association between the polymorphism of XRCC1 and breast cancer risk among studies of Asian countries. In Asian countries the Arg/Gln versus Arg/Arg (OR = 0.98, 95% CI: 0.88-1.10) and Gln/Gln+Arg/Gln versus Arg/Arg (OR = 1.05, 95% CI: 0.95-1.18) were not associated with increased risk of breast cancer. On the other hand, both Gln/Gln versus Arg/Arg (OR = 1.46, 95% CI: 1.19-1.79) and Gln/Gln versus Arg/Gln+Arg/Arg (OR = 1.49, 95% CI: 1.22-1.81) increased the risk. Therefore, it could be concluded that 399Gln allele might act as a recessive allele in its association with breast cancer risk.