DNA repair gene XRCC3 polymorphisms and cancer risk: a meta-analysis of 48 case-control studies
DNA repair gene XRCC3 polymorphisms and cancer risk: a meta-analysis of 48 case-control studies
复制标题
DOI：
10.1038/sj.ejhg.5201681
复制
发表时间：
2006-10-01
影响因子：
5.2
通讯作者：
Li, Yao
中科院分区：
文献类型：
--
作者：
Han, Shizhong;Zhang, Hong-Tao;Li, Yao
X 射线修复交叉互补组 3 (XRCC3) 是高度怀疑的癌症易感性候选基因。然而，癌症中 XRCC3 多态性（4541A > G、Thr(241)Met、17893A > G）的关联研究显示了相互矛盾的结果。因此，我们进行了荟萃分析，以更好地评估所谓的关联。我们选择了 48 项符合条件的病例对照研究进行荟萃分析，其中包括 24 975 名癌症患者和 34 209 名对照。总体而言，携带 XRCC3 Met/Met 基因型的个体在隐性遗传模型下表现出较小的癌症风险。亚组和荟萃回归分析证明了 XRCC3 Met/Met 基因型在不同亚组癌症易感性中的作用的不同情况。特别是，乳腺癌的风险显着增加（OR，1.14；P = 0.0004；95% CI，1.06-1.23；异质性 P = 0.37），头颈癌、膀胱癌的风险升高但不显着，令人惊讶的是，非黑色素瘤皮肤癌的风险显着降低（OR，0.76；P = 0.007；95% CI， 0.62-0.93；异质性 P = 0.61）。在基于人群的病例对照研究中观察到癌症风险显着升高，但在巢式或医院研究中未观察到。同样，我们发现在显性遗传模型下，A4541G 患癌症的风险显着增加，而 A17893G 患癌症的风险却降低。我们的荟萃分析结果支持 XRCC3 可能代表一种低外显率的易感基因，特别是对于乳腺癌、膀胱癌、头颈癌和非黑色素瘤皮肤癌。应该需要一项更大规模的研究来进一步评估特定种族人群中 XRCC3 多态性和组织特异性癌症风险的基因-基因和基因环境相互作用。
The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility. However, association studies on the XRCC3 polymorphisms (4541A > G, Thr(241)Met, 17893A > G) in cancer have shown conflicting results. Therefore, we performed a meta-analysis to better assess the purported associations. Forty eight eligible case-control studies including 24 975 cancer patients and 34 209 controls were selected for our meta-analysis. Overall, individuals carrying the XRCC3 Met/Met genotype showed a small cancer risk under a recessive genetic model. The subgroup and meta-regression analysis demonstrated different scenarios concerning the XRCC3 Met/Met genotype's role in cancer susceptibility for different subgroups. Specially, there was a significantly increased risk of breast cancer (OR, 1.14; P = 0.0004; 95% CI, 1.06-1.23; P = 0.37 for heterogeneity), elevated but not significant risk of cancer for head and neck, bladder, surprisingly, a significantly decreased risk of non-melanoma skin cancer (OR, 0.76; P = 0.007; 95% CI, 0.62-0.93; P = 0.61 for heterogeneity). A significantly elevated risk of cancer was observed in population-based case-control studies but not in nested or hospital based studies. Similarly, we found a significantly increased risk of cancer for A4541G and a decreased risk for A17893G under dominant genetic models. Our meta-analysis results support that the XRCC3 might represent a low-penetrance susceptible gene especially for cancer of breast, bladder, head and neck, and non-melanoma skin cancer. A single larger study should be required to further evaluate gene-gene and gene environment interactions on XRCC3 polymorphisms and tissue-specific cancer risk in an ethnicity specific population.