HLA-DRB1座位的等位基因多态性与乳腺癌遗传易感关系的研究

Study on the association between HLA-DRB1 allele polymorphism and the genetic susceptibility with Breast Cancer

目的研究乳腺癌与人类白细胞抗原Ⅱ类基因DRB1座位等位基因的相关性。方法病例组为临床已确诊的乳腺癌患者112例,均使用LUMINEX 200液相分析平台,采用序列微珠综合分析实验技术(FLOW-SSO)方法进行HLA分型。对照组为"中华造血干细胞志愿捐献者资料库"广东分库的志愿捐献者20 621例,采用FLOW-SSO和SBT方法进行HLA分型,对不确定结果采用PCR-SSP分型试剂进行确认。所有检测样本的DNA使用瑞士TECAN公司DNA提取自动工作站从EDTA-K2抗凝的外周全血中抽提。结果在112例乳腺癌患者中共检测到HLA-DRB1座位等位基因27个。病例组与对照组两个群体的HLA-DRB1座位等位基因的分布差异有统计学意义(χ2=42.39,P<0.05)。其中HLA-DRB1*0408在病例组中的分布频率高于对照组(χ2=4.19,P<0.05),相对危险度RR=6.34(χ2=4.20,P<0.05);HLA-DRB1*0901在病例组中的等位基因频率为0.205 4,高于对照组中的0.150 1(χ2=5.33,P<0.05),相对危险度RR=1.63(χ2=6.50,P<0.05);HLA-DRB1*0701在病例组中的分布频率仅为0.026 8,低于对照组中的0.086 1(χ2=10.00,P<0.05),相对危险度RR=0.24(χ2=11.37,P<0.05)。其他等位基因的频率分布差异及相对危险度经χ2检验差异无统计学意义(P>0.05)。结论 HLA-DRB1*0408、HLA-DRB1*0901可能是乳腺癌的易感基因,而HLA-DRB1*0701可能是乳腺癌的保护基因。

Objective To examine the correlation between breast cancer and HLA-DRB1 alleles of class Ⅱ, Methods Using FLOW-SSO HLA typing methods and LUMINEX 200 liquid analysis platform to 112 cases of breast cancer patients, which have been confirmed by clinical cases group. Control group is the 20,621 volunteer donors, which from Guangdong sub-library,＂Chinese hematopoietic stem cell volunteer donor database ＂. PCR-SSP typing confirmed the ambiguous allele pairs. All DNA samples extracted from the peripheral blood of anticoagulant EDTA K2 by automatically extracted station of Swiss TECAN Company. Results 27 alleles of HLA-DRB1 were found in the 112 patients with breast cancer. The distribution of the allele HLA-DRB1 between the ease group and control group had the statistically significance（x2 = 42.39, v= 27, P〈0.05）. By further analysis, we found that the allele frequency of HLA DRB1 ＊ 0408 in case group was higher than that of the control group（AFcase group =0. 008 9,AF control group =0. 001 4,X2=4.19,P%0. 05）. Relative risk RR=6.34（X2=4. 20,P%0. 05）. The allele frequency of HLA-DRB1＊ 0901 in case group was 0. 205 4,while in control group was 0. 150 1,the case group was higher thant hat of the control group（x2 =5.33,P%0.05）. Relative risk RR=1.63（X2=6.50,P〈0.05）. The allele frequency of HLA DRB1＊ 0701 is 0. 026 8 in case group,while AF= 0. 086 1 in control group（x2 =10.00,P%0.05）. Relative risk RR=0.24（X2 =11.37,P〈0.05）. Other allele＇s frequency distributions and relative risk,which were examined by X2 test（P〉0.05） ,had no statistically significance. Conclusion HLA-DRB1＊ 0408 and HLA-DRB1＊ 0901 may be the two susceptibility genes of the breast cancer,and HLA-DRB1 ＊ 0701 may be the protected gene avoiding the breast cancer.