新疆维吾尔族和汉族乳腺癌与HLA-DRB1基因多态性的分析

Relationship between the polymorphism of HLA-DRB1 allele and susceptibility to breast cancer in Uygur and Han patients in the Xinjiang Region

目的 乳腺癌的发生和发展与遗传因素有确切的相关性。人类白细胞抗原DRB1（human leukocyte antigen DRB1,HLA-DRB1）与乳腺癌发生发展相关,且HLA-DRB1基因多态性具有种族和地域差异。本研究对新疆维吾尔族和汉族乳腺癌遗传易感性与HLA-DRB1基因多态性的关系进行探讨,旨在探寻新疆乳腺癌遗传易感预警信号,为明确HLA-DRB1基因多态性在乳腺癌发生中的作用及其可能的作用机制提供理论依据。方法 采用聚合酶链反应-序列特异性引物（polymerase chainreaction-sequence specific primers,PCR-SSP）和毛细管电泳测序（capillary electrophoresis sequencing,CE）技术,分析2013-01-01-2014-07-31新疆医科大学附属肿瘤医院198例乳腺癌患者（维吾尔族和汉族分别为98和100例）与230例体检健康者（维吾尔族和汉族各115例）的HLA-DRB1等位基因多态性;χ~2检验分别验证新疆地区乳腺癌、维吾尔族乳腺癌和汉族乳腺癌与其对照组间HLA-DRB1等位基因频率分布有无差异。结果 等位基因间比较,新疆地区乳腺癌与其健康对照组间DRB1＊01和DRB1＊16基因频率分布的差异均有统计学意义,χ~2=10.589,P〈0.05,OR=3.377;χ~2=12.408,P〈0.05,OR=0.354;维吾尔族乳腺癌与其对照组间DRB1＊01基因频率分布的差异有统计学意义,χ~2=10.180,P〈0.05,OR=4.551;汉族乳腺癌与其对照组间DRB1＊15和DRB1＊16基因频率分布的差异有统计学意义,χ~2=9.562,P〈0.05,OR=0.481;χ~2=9.463,P〈0.05,OR=0.135。等位基因亚型分析显示,维吾尔族乳腺癌DRB1＊0102基因频率分布高于对照组,差异有统计学意义,χ~2=6.805,P〈0.05,OR=9.745;汉族乳腺癌DRB1＊1501和DRB1＊1602的基因频率分布均低于对照组,差异有统计学意义,χ~2=9.535,P〈0.05,OR=0.454;χ~2=9.463,P〈0.05,OR=0.135。结论 维吾尔族和汉族乳腺癌遗传易感性可能与HLA-DRB1基因多态性相关,HLA-DRB1＊0102可能是维吾尔族乳腺癌的易感基因,而HLA-DRB1＊1501和HLA-DRB1＊1602可能是汉族乳腺癌的保护基因。

OBJECTIVE There is a definite correlation between the occurrence and development of breast cancer and genetic factors. HLA-DRB1 is associated with breast cancer and its allele polymorphisms have ethnic and regional diversi- ty. This study would discuss the relationship between the genetic susceptibility to Uygur and Han breast cancer and HLA-DRB1 allele polymorphisms, aim to explore breast cancer susceptibility warning signal in Xinjiang, and provide a theoretical basisis to explicit HLA-DRB1 polymorphisms role in breast cancer and its possible mechanism. METHODS PCR-SSP and CE were applied to analyze HLA-DRB1 polymorphisms in 198 patients with breast eancer（Uygur and Hanwere 98,100 cases）and 230 healthy controls（Uygur and Han each 115 cases）from January 1,2013 to July 31,2014 in Tumor Hospital of Xinjiang Medical University. Chi-square test was used to determine the differences of HLA-DRB1 al- lele frequency distributed between breast cancer groups among Uygur and Han and their controls in Xinjiang region re- spectively. RESULTS Differences in gene frequency distribution of DRB1 ＊ 01 and DRB1 ＊ 16 between women with breast cancer and its healthy control were statistically significant in Xinjiang Region（ χ2 = 10. 589, P〈0.05, OR= 3.377 ;χ2 =12. 408, P〈0.05, OR=0. 354）, and DRB1 ＊ 01 in Uygur patients（χ2 =10. 180, P〈0.05, OR=4. 551）, and also DRB1 ＊ 15 and DRB1 ＊ 16 in Han patients（χ2 =9. 562, P〈0.05, OR1=0. 481; χ2 =9. 463, P〈0.05, OR=0. 135）. Allele in subtype analysis showed that DRB1 ＊ 0102 alleles was significantly more frequent in Uygur patients in compari- son to controls（χ2 =6. 805, P〈0.05, OR=9. 745）, DRB1 ＊ 1501 and DRB1＊ 1602 alleles were less frequent in Han pa- tients compared with controls（χ2 =9. 535, P〈0.05, OR=0. 454; χ2 =9. 463, P〈0.05, OR=0. 135）. CONCLUSIONS The genetic susceptibility of Uygur and Han women with breast cancer may be associated with HLA-DRB1 polymorphism： HLA-DRB1 ＊ 0102 may be the susceptibility gene of the Uygur patients, HLA-DRB1 ＊1501 and HLA-DRB1 ＊1602 may be the protected gene of Han patients.