中文摘要：

目的探讨DNA同源重组修复基因RAD51—G135C和XRCC3-C241T多态性与伴重现染色体易位急性髓系白血病（AML）发生的关系。方法共收集625例初治原发性AML患者的骨髓、806名患者一级亲属和704名与患者无血缘关系正常人的外周血样本，常规提取基因组DNA。用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法分析RAD51-G135C和XRCC3-C241T基因多态性。选取XRCC3-C241T不同基因型细胞系进行体外照射，用TaqMan实时定量PCR法检测CBFβ-MYH11融合基因mRNA的相对表达量。结果同正常人和一级亲属比较，XRCC3-C241T变异基因型（C／T＋T／T）能明显提高inv（16）／t（16；16）／CBFβ-MYH11（＋）AML的发病风险，风险值分别提高了6．22倍（P〈0．001）和6．99倍（P〈0．001）；同正常人和一级亲属比较，RAD51-G135C纯合变异基因型（C／C）亦能明显提高inv（16）／t（16；16）／CBVβ-MYH11（＋）AML的发病风险，风险值分别提高了0．87倍（P=0．010）和1．15倍（P=0．001）。经照射后，XRCC3-C241T纯合变异型HL-60细胞系CBFβ-MYH11融合基因mRNA表达量是野生型KG1a细胞系的59．49倍。RAD51-G135C和XRCC3-C241T多态性位点基因型与t（15；17）／PML—RARα（＋）AML、t（8；21）／AML1-ETO（＋）AML和11q23异常AML发生风险无明显相关性。结论XRCC3-C241T变异基因型和RAD51-G135C纯合变异基因型可显著增高inv（16）／t（16；16）／CBFβ-MYH11（＋）AML发生的风险。

英文摘要：

Objective To investigate the relationship between DNA homologous recombination （HR） repair genes RAD51-G135C/XRCC3-C241T polymorphisms and development of acute myeloid leukemia （AML） with recurrent chromosome translocation. Methods Genomic DNA was extracted from bone marrow cells of 625 de novo AML patients and peripheral blood cells of 806 patient family members and 704 unrelated volunteers. Genotypes of RAD51-G135C and XRCC3-C241T were analyzed by PCR-RFLP. Cell lines with genotypes differed from XRCC3-C241T were selected and irradiated in vitro. The CBFI3-MYH11 fusion gene was detected by TaqMan real-time PCR. Results The XRCC3-C241T variant （C/T ＋ T/T） showed 6.22-fold and 6.99-fold increase in the risk of developing the AML with inv （ 16 ）/t （ 16;16 ）/CBFβ- MYH11 as compared with the volunteer and family member controls respectively; the RAD51-G135C homozygote-type （C/C） variant showed 0.87-fold （ P = 0. 010） and 1.15-fold （ P = 0. 001 ） respectively increase in the risk of this subtype AML. In the irradiated group, the CBFβ-MYH11 mRNA level in HL-60 ceils was 59.49 times increased than that in KGla cells. However, the RAD51-G135C and XRCC3-C241T variants had no correlations with the risk of development of t（ 15;17 ）/PML-RARcL （ ＋ ）AML, t（8;21 ）/AML1-ETO （ ＋ ） AML and 1 lq23 AML subtypes. Conclusion The XRCC3-C241T variant and the RAD51-G135C homozygote-type significantly increase the risk of the development of AML with inv（16）/t（16;16）/CBFβ-MYHI 1.