中国湖南家族性和早发性乳腺癌BRCA1和BRCA2基因突变分析

BRCA1 and BRCA2 gene mutations of familial breast cancer and early-onset breast cancer from Hunan Province in China

背景与目的:BRCA1和BRCA2基因是已经证实的乳腺癌遗传易感基因,与家族性及早发性乳腺癌密切相关。本研究旨在分析中国湖南省家族性和早发性乳腺癌中BRCA1和BRCA2基因的突变位点及携带情况。方法:以来自湖南地区的50例家族性和早发性乳腺癌(发病年龄≤35岁)为研究对象,其中26例(52%)有乳腺癌家族史。由静脉血提取基因组DNA,对BRCA1和BRCA2基因的全部编码序列进行扩增。突变分析由变性高效液相色谱分析(DHPLC)进行预筛,之后进行DNA测序证实。结果:在50例乳腺癌患者中发现有5种致病性突变,其中2种为新发现突变——BRCA2基因无义突变2372C>G和移码突变2808delACAA。BRCA1基因中发现一种已报道的无义突变220C>T;其他两种为已报道的BRCA2移码突变位点1796delTTTAT和6275delTT。我们还发现4个未知功能的突变位点(UV)及11个基因多态性位点。湖南家族性乳腺癌中BRCA1突变率4%低于BRCA2突变率16%。结论:在中国湖南人群中,BRCA2基因的突变对于遗传性乳腺癌的发生可能具有较重要意义;新发现的2个突变位点可能是中国人群中的特有突变;湖南地区BRCA1在家族性乳腺癌中突变率明显低于国内外报道,而BRCA2突变发生率与西方国家相近,但明显高于国内其他地区,这可能是中国湖南人群中的特有特征。

Background and purpose： BRCA1 and BRCA2 gene are known as breast cancer susceptibility genes. Both of them are closely associated with familial breast cancer and early onset breast cancer. The objective of our research is to investigate the prevalence of BRCA1 and BRCA2 gene mutations among Hunan patients with familial or at early onset breast cancer. Methods： 50 breast cancer patients with familial history or have suffered from breast cancer at the age of less than 35 years old were analyzed, among whom 26 of the patients（52%） had at least one relative affected. A comprehensive BRCA1 and BRCA2 mutation analysis was performed through denaturing high- performance liquid chromatography （DHPLC） and subsequent DNA direct sequencing. Results： Five mutations were identified that included 2 novel mutations （nonsense mutation 2372C〉G and frameshift mutation 2808delACAA in BRCA2 gene） and 3 previously reported mutations （nonsense mutation 220C〉T in BRCA1 gene, frameshift mutations 1796delTTTAT and 6275delTT in BRCA2 gene）. Additional 4 variants of unknown and 11I gene polymorphisms were detected. The mutation frequency of BRCA1 and BRCA2 in patients with breast cancer family history was 4% and 16%, respectively. Conclusion： The BRCA2 may contribute to mutation more than BRCA1 in familial breast cancer of Hunan population. Two novel mutations in BRCA2 may be mutations characterized to familial breast cancer of Chinese Hunan population. The mutation frequency of BRCAI in familial breast cancer patients from Hunan is obviously lower than the western country and the other province of China. However, the mutation frequency of BRCA2 in the Hunan population is similar to the western country but much higher than the other province of China. That is probably the characteristic of BRCA mutation in Hunan population.