Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan, R.O.C.
Anticancer Res. 2010 Feb;30(2):529-33.
The DNA repair gene XRCC4, a member of the protein family involved in non-homologous end-joining repair pathway, plays a major role in repairing DNA double-strand breaks. XRCC4 is important in maintaining the overall genome stability, and it is also thought to play a key role in human carcinogenesis. We investigated some novel polymorphic variants of XRCC4, including C-1622T (rs7727691), G-1394T (rs6869366), G-652T (rs2075685), C-571T (rs2075686), intron3 DIP (rs28360071), S247A (rs3734091) and intron7 DIP (rs28360317), and analyzed the association of specific genotype with susceptibility to childhood leukemia.
In total, 266 children with leukemia and 266 age-matched healthy controls recruited from the China Medical Hospital in Central Taiwan were genotyped investigating the association of these polymorphisms with childhood leukemia.
We found differences in frequency of the XRCC4 G-1394T and intron 3 genotype, but not the XRCC4 codon 247, or intron 7, between the childhood leukemia and control groups. Our data indicated the G allele of G-1394T and deletion of intron 3 are clear risk factors of susceptibility to childhood leukemia (p=0.0022 and 0.0075). As for XRCC4 C-1622T and C-571T, there was no difference in the distribution between the two groups. The analysis of joint effect for XRCC4 G-1394T and intron 3 showed that individuals with GT at G-1394T and DD at intron 3 present the highest potential for developing childhood leukemia than other groups (odds ratio=4.94, 95% confidence interval=1.01-24.27, p=0.0404).
Our findings suggest that the G allele of XRCC4 G-1394T and deletion of intron 3 may be responsible for childhood leukemia and may be useful in early detection of child leukemia.
DNA 修复基因 XRCC4 是参与非同源末端连接修复途径的蛋白家族的成员，在修复 DNA 双链断裂方面发挥着重要作用。XRCC4 对于维持基因组的整体稳定性至关重要，并且被认为在人类致癌作用中也发挥着关键作用。我们研究了 XRCC4 的一些新的多态性变异，包括 C-1622T（rs7727691）、G-1394T（rs6869366）、G-652T（rs2075685）、C-571T（rs2075686）、内含子 3 DIP（rs28360071）、S247A（rs3734091）和内含子 7 DIP（rs28360317），并分析了特定基因型与儿童白血病易感性的关联。
共招募了来自中国台湾中部中国医药大学附属医院的 266 名白血病患儿和 266 名年龄匹配的健康对照者，研究了这些多态性与儿童白血病的关系。
我们发现 XRCC4 G-1394T 和内含子 3 基因型的频率存在差异，但 XRCC4 密码子 247 或内含子 7 则没有差异。我们的数据表明，G-1394T 的 G 等位基因和内含子 3 的缺失是儿童白血病易感性的明确危险因素（p=0.0022 和 0.0075）。至于 XRCC4 C-1622T 和 C-571T，两组之间的分布没有差异。XRCC4 G-1394T 和内含子 3 的联合作用分析表明，G-1394T 为 GT 且内含子 3 为 DD 的个体发生儿童白血病的可能性最高，高于其他组（比值比=4.94，95%置信区间=1.01-24.27，p=0.0404）。
我们的研究结果表明，XRCC4 G-1394T 的 G 等位基因和内含子 3 的缺失可能与儿童白血病有关，并且可能有助于儿童白血病的早期检测。
