家族性乳腺癌家系成员乳腺癌易感基因突变的研究

目的研究河北省地区家族性乳腺癌家系中的患者及健康一级亲属乳腺癌易感基因1（BRCAl）和乳腺癌易感基因2（BRCA2）突变位点及携带情况。方法研究对象为2002年6月至2008年5月河北医科大学第四医院接诊的乳腺癌患者及其亲属，分别来自12个独立的汉族家族性乳腺癌家系，该家系中有2个及2个以上一级或二级亲属乳腺癌患病史，研究病例包括13例患者及46例健康一级亲属，共59例样本。由外周血提取基因组DNA，采用聚合酶链反应一单链构象多态性分析（PCR—SSCP）和基因测序技术对国内外报告中常见的4个BRCAl／BRCA2突变热点区域（BRCAl：外显子2、11、20；BRCA2外显子11）进行检测。结果发现1个BRCAl突变位点（4193insA）和1个BRCA2突变位点（5329insT），全部为移码突变；发现4个变异位点（BRCAl：4165T〉A、287G〉C，BRCA2：6251G〉T、5416C〉A），4193insA、5329insT、287G〉C携带者的家系中均有3例乳腺癌患者。结论BRCAl（4193insA）、BRCA2（5329insT）以及BRCAl：4165T〉A、287G〉C和BRCA2：6251G〉T、5416C〉A可能是河北省家族性乳腺癌相关性突变位点，其携带者家系中乳腺癌发病率明显升高，建议对其一级亲属密切随访或尽早进行手术或药物干预。

BRCA1 and BRCA2 gene mutations in familial breast cancer

Objective To investigate nmtations and the carrying of breast cancer susceptibility gene （BRCA） 1 and BRCA2 among patients and their healthy first degree relatives in family constellation of breast cancer in Hebei province. Methods This study involved breast cancer patients treated in the Fourth Affiliated Hospital of Hebei Medical University from June, 2002 to May, 2008 and their relative, including 59 samples （ 13 patients and 46 healthy first degree relatives from 12 independent families of Han Nationality in which 2 or more first or second degree relatives had breast cancer history. Four BRCA1/BRCA2 mutation hot spots （BRCA1 ： Exon2, 11 ,20; BRCA2： Exonl 1 ） commonly reported in literature were detected by extracting DNA from peripheral blood, using PCR-SSCP and gene sequencing technology. Results One BRCA1 mutation site （4193insA） and one BRCA2 mutation site（5329insT）were found with frame shift mutations; four variation sites （ BRCA1：4165T〉A and 287G〉C, BRCA2 ： 6251G〉T and 5416C〉A） were observed. In every families which carrying 4193insA, 5329insT, 287G〉C individually, 3 eases which had breast cancer were found. Conclusion BRCA1 （4193insA）, BRCA2（5329insT） , BRCAI ： 4165T〉A and 287G〉C and BRCA2： 6251G〉T and 5416C〉A could be the mutation sites in familial breast cancer in Hebei Province. The families calxying those sites show a higher incidence of breast cancer. Therefore, close follow-ups or surgical or drug interventions are recommended for the first-degree relatives of the breast cancer patients.