散发性乳腺癌与BRCA2基因rs206115位点多态性的相关分析
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摘要
目的探讨散发性乳腺癌与乳腺癌易感基因2(BRCA2)基因rs206115位点多态性的相关性。方法收集2015年12月至2016年12月就诊于内蒙古医科大学附属医院乳腺外科并经病理确诊的原发性散发性乳腺癌患者(病例组)和良性乳腺疾病患者(对照组)各101例,采用PCR及直接测序方法分析患者BRCA2基因rs206115位点多态性。使用SPSS17.0软件进行统计学分析。结果汉族和蒙古族患者rs206115位点均可检测出3种基因型:AA型、AG型和GG型。与对照组比较病例组rs206115位点基因多态性差异无统计学意义(χ~2=3.490,P=0.175),与对照组比较,病例组中等位基因A分布频率显著增高(χ~2=4.259,P=0.039)。结论 BRCA2基因rs206115位点A基因可能是蒙汉族散发性乳腺癌的易感基因之一。
Objective To analyze the correlation between polymorphism of the BRCA2 gene rs206115 loci and sporadic breast cancer in Inner Mongolia. Methods We enrolled patients from the Affiliated Hospital of Inner Mongolia Medical University from December 2015 to December 2016 who underwent breast surgery and were confirmed by pathology,resulting in a total of 101 cases of primary sporadic breast cancer(case group) and benign breast diseases(control group). DNA was extracted from blood samples and analyzed using polymerase chain reaction(PCR) and direct sequencing methods for determining the BRCA2 gene rs206115 loci polymorphism. SPSS 17.0 was used for statistical analysis. Results In this experiment,regardless of whether the patients were Han or Mongolian,the rs206115 loci could be detected in 3 kinds of genotypes:AA,AG,and GG. The BRCA2 gene rs206115 locus gene polymorphism was not significantly different between the case and control groups(χ~2=3.490,P = 0.175). The A allele frequency of the BRCA2 gene rs206115 loci in the case group was significantly increased compared to the control group(χ~2=4.259,P = 0.039). Conclusion The A allele of rs206115 may be one of the susceptibility alleles in sporadic breast cancer in Mongolian and Han populations.
Objective To analyze the correlation between polymorphism of the BRCA2 gene rs206115 loci and sporadic breast cancer in Inner Mongolia. Methods We enrolled patients from the Affiliated Hospital of Inner Mongolia Medical University from December 2015 to December 2016 who underwent breast surgery and were confirmed by pathology,resulting in a total of 101 cases of primary sporadic breast cancer(case group) and benign breast diseases(control group). DNA was extracted from blood samples and analyzed using polymerase chain reaction(PCR) and direct sequencing methods for determining the BRCA2 gene rs206115 loci polymorphism. SPSS 17.0 was used for statistical analysis. Results In this experiment,regardless of whether the patients were Han or Mongolian,the rs206115 loci could be detected in 3 kinds of genotypes:AA,AG,and GG. The BRCA2 gene rs206115 locus gene polymorphism was not significantly different between the case and control groups(χ~2=3.490,P = 0.175). The A allele frequency of the BRCA2 gene rs206115 loci in the case group was significantly increased compared to the control group(χ~2=4.259,P = 0.039). Conclusion The A allele of rs206115 may be one of the susceptibility alleles in sporadic breast cancer in Mongolian and Han populations.
引文
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[3]HEDAU S,BATRA M,SINGH UR,et al.Expression of BRCA1and BRCA2 proteins and their correlation with clinical staging in breast cancer[J].J Cancer Res Ther,2015,11(1):158-163.DOI:10.4103/0973-1482.140985.
[4]MCPHERSON K,STEEL CM,DIXON JM.Breast cancer-epidemiology,risk factors,and genetics[J].BMJ,2000,321(7261):624-628.DOI:10.1136/bmj.321.7261.624.
[5]GODET I,GILES DM.BRCA1 and BRCA2 mutations and treatment strategies for breast cancer[J].Integr Cancer Sci Ther,2017,4(1):10.DOI:10.15761/ICST.1000228.
[6]BAYNES C,HEALEY CS,POOLEY KA,et al.Common variants in the ATM,BRCA 1,BRCA2,CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk[J].Breast Cancer Res,2007,9(2):R27.DOI:10.1186/bcr3591.
[7]FIGUEIREDO JC,BROOKS JD,CONTI DV,et al.Risk of contralateral breast cancer associated with common variants in BRCA1 and BRCA2:potential modifying effect of BRCA1/BRCA2 mutation carrier status[J].Breast Cancer Res Treat,2011,127(3):819-829.DOI:10.1007/s10549-010-1285-1.
[8]刘璐.BRCA2基因启动子区多态性在乳腺癌预后中的研究及BRCA2基因启动子的克隆和分析[D].苏州大学,2013.
[9]马金柱,刘明.乳腺癌易感基因1、2在散发性乳腺癌中的表达及意义[J].中华医学杂志,2014,90(44):3515-3518.DOI:10.3760/cma.j.issn.0376-2491.2014.44.015.
[10]SHIMELIS H,MESMAN RLS,VON NICOLAI C,et al.BRCA2 hypomorphic missense variants confer moderate risks of breast cancer[J].Cancer Res,2017,77(11):2789-2799.DOI:10.1158/0008-5472.CAN-16-2568.
[11]王雯,马志萍,古丽那尔·阿布拉江,等.维吾尔族和汉族散发性乳腺癌患者BRCA1/2基因突变的检测[J].基础医学与临床,2017,37(1):50-55.DOI:10.16352/j.issn.1001-6325.2017.01.009.
[12]DANFORTH DN.Genomic changes in normal breast tissue in women at normal risk or at high risk for breast cancer[J].Breast Cancer(Auckl),2016,10(1):109-146.DOI:10.4137/BCBCR.S39384.
[13]HAMDI Y,SOUCY P,KUCHENBAEKER KB,et al.Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential alleic expression:identification of a modifier of breast cancer risk at locus 11q22.3[J].Breast Cancer Res Treat,2017,161(1):117-134.DOI:10.1007/s10549-016-4018-2.
[14]KUCHENBAECKER KB,MCGUFFOQ L,BARROWDALE D,et al.Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers[J].J Nat Cancer Inst,2017,109(7):1-15.DOI:10.1093/jnci/djw302.