河北省家族性和散发性乳腺癌易感基因1/2突变的研究

目的探讨河北省家族性和散发性乳腺癌患者乳腺癌易感基因(BRCA)1/2的突变位点及携带情况。方法采用聚合酶链反应-单链构象多态性分析和基因测序技术对18例家族性乳腺癌患者、50例散发性乳腺癌患者、23例乳腺良性疾病患者及20例健康对照组血样标本的基因组DNA进行BRCA1/2基因突变的检测。定性资料采用χ2检验和Fisher's确切概率法进行分析,定量资料采用t检验进行分析。结果 68例乳腺癌患者基因突变率为7.35%(5/68),均发生在BRCA1基因(162ATTTTT;4142GTTGTG;4196CAACAT;4196delA,4142GTTGTG;5379GAAAAA),无BRCA2基因突变,BRCA1基因的突变率高于BRCA2基因(χ2=4.829,P=0.028);其中,18例家族性乳腺癌基因突变3例,50例散发性乳腺癌突变2例,二者间差异无统计学意义(χ2=3.117,P=0.111)。乳腺良性疾病患者未见BRCA1/2基因突变。健康对照组未见BRCA1基因突变,但有1例BRCA2基因突变[TTTCAGA-TGTCAA(6291insG,6294delG)]。家族性乳腺癌患者、散发性乳腺癌患者、乳腺良性疾病患者和健康对照组的BRCA1基因突变率差异有统计学意义(χ2=8.248,P=0.041)。在1例家族性乳腺癌标本中发现1个核苷酸多态性位点,位于BRCA1第20外显子下游第35个碱基处GA(IVS20+35GA)。结论本研究丰富了中国人群BRCA1/2基因的突变谱,并为将来乳腺癌的普查和临床基因检测提供了筛查模式。

BRCA1/2 gene mutations of familial and sporadic breast cancer from Hebei Province in China

Objective To investigate the prevalence of BRCA（breast cancer susceptibility gene）1/2gene mutations among familial and sporadic breast cancer patients in Hebei Province of China.Methods The BRCA1/2gene mutation and genomic DNAs from peripheral blood cells of 18familial breast cancer patients,50 sporadic breast cancer patients,23breast benign tumor patients and 20health controls were studied using polymerase chain reaction-single strand conformation polymorphism analysis and DNA sequencing.Chi-square test or Fisher＇s exact propability test was used for analysis of qualitative data,and Student＇s t test was used for analysis of quantitative data.Results The incidence of gene mutation in breast cancer patients was 7.35%（5/68）.All of these mutations（162ATT〉TTT,4142GTT〉GTG,4196CAA〉CAT,4196delA,4142GTT〉GTG,5379GAA〉AAA） were localized in BRCA1instead of BRCA2.The mutation rate of BRCA1was much higher than that of BRCA2（χ^2=4.829,P=0.028）.Of the 68breast cancer patients,the BRCA1mutation rate of familial breast cancer（16.67%,3/18）was higher than that of sporadic breast cancer（4.00%,2/50）,but there was no significant difference（χ^2=3.117,P=0.111）.No BRCA1/2mutation was found in the breast benign tumor patients.No BRCA1 mutation but a BRCA2 mutation（TTTCAGA〉TGTCAA（6291insG,6294delG））was found in the health controls.There was a statistical difference in the BRCA1mutation rate among the familial breast cancer patients,the sporadic breast cancer patients,the breast benign tumor patients and the health controls（χ^2=8.248,P=0.041）.In addition,a mononucleotide polymorphism at the 35th base downstream from BRCA1exon 20G〉A（IVS20＋35G〉A）was found in one of the familial breast cancer patients.Conclusions Our data has enriched the information of mutation spectrum of BRCA1/2gene in Chinese population and also offer a recommended screening mode for clinical genetic testing policy in China.