摘要
背景与目的:BRCA1和BRCA2是通过家系连锁分析确定的与乳腺癌、卵巢癌家族高度相关的两个基因,目前国内关于中国汉族遗传性乳腺癌BRCA1和BRCA2突变研究的样本量都不大,而且大部分研究仅检测了BRCA1或部分BRCA2,并不能真正反映汉族遗传性乳腺癌的遗传特征。本研究旨在建立中国汉族人群遗传性乳腺癌患者中BRCA1和BRCA2的突变谱,并确定高危突变的家族特征。方法:来自3个中心的219个独立的家系纳入本研究,每个家系中的先证者进行BRCA1和BRCA2全外显子以及外显子内含子拼接区的突变检测。结果:219例患者检测到23例致病性突变,7例位于BRCA1,16例位于BRCA2。BRCA1和BRCA2的突变率与家系特征有关,家族性乳腺癌/卵巢癌患者BRCA1和BRCA2的突变率分别14.3%(1/7)和28.6%(2/7);早发性遗传性乳腺癌患者BRCA1的突变率为22.2%(2/9);而在非早发性遗传性乳腺癌患者BRCA2的突变率明显高于BRCA1(7.8%,6/77vs0%,0/77,P=0.028)。结论:BRCA1和BRCA2突变率与家族特征有关,在非早发性遗传性乳腺癌家族中BRCA2突变值得关注。
Background and purpose：BRCA1 and BRCA2 were susceptibility genes for breast and ovarian cancer identified through pedigree linkage analysis.Limited data of BRCA1/2 mutations in Chinese population was available since previous reports either focused on BRCA1 or were relatively small series.The main purpose of this China wide multi center study is to establish a BRCA1 and BRCA2 mutation profile and to identify those families with high frequencies of mutations in these genes.Methods：A consecutive series of 219 unrelated probands of hereditary breast cancer families from three districts in China were recruited in this study.The entire coding exons of BRCA1 and BRCA2 genes were analyzed using DHPLC followed by DNA sequencing.Results：A total of 23 deleterious mutations were identified,7 in BRCA1 and 16 in BRCA2.The frequencies of BRCA1 and BRCA2 mutations were 14.3%（1/7）and 28.6%（2/7）in the HBOC families.And the frequency of BRCA1 mutations in early onset breast cancer patients were 22.2%（2/9）.Prevalence of BRCA2 mutations was higher than that of BRCA1 in non-early-onset breast cancer patients with family history（n=77,7.8% vs 0%,P=0.03）.Conclusions：The frequency of BRCA1/2 mutations is related to the family structure that a proband presented.Deleterious mutations in BRCA2 is worthy of attention in non-early-onset Han hereditary breast cancer cases.
出处
《中国癌症杂志》
CAS
CSCD
2008年第5期370-375,共6页
China Oncology
基金
国家自然科学基金(30371580)
863项目(2002BA711A08-34)
作者简介
通讯作者：邵志敏E-mail：zhimingshao@yahoo．com
