Koumpis Chrissovaladis, Dimitrakakis Constantine, Antsaklis Aris, Royer Robert, Zhang Shiyu, Narod Steven A, Kotsopoulos Joanne
Women's College Research Institute, Toronto, ON, Canada.
Hered Cancer Clin Pract. 2011 Nov 15;9(1):10. doi: 10.1186/1897-4287-9-10.
Inheritance of a mutation in either BRCA1 or BRCA2 accounts for approximately 5% of all breast cancer cases, but varies by country. Investigations into the contribution of BRCA mutations to breast cancer incidence in Greece have been, for the most part, limited by small sample sizes and by the use of cases selected for their family history of cancer. The aim of the current study was to estimate BRCA mutation frequencies in breast cancer patients unselected for family history.
To do so, we enrolled 127 unselected women with breast cancer from the Alexandra Hospital in Athens, Greece, a large public hospital in the city. Mutations in BRCA1 and BRCA2 were detected using a combination of techniques and were confirmed by direct sequencing. Two large genomic deletions were sought using mutation-specific assays. A detailed family history of cancer was obtained from each patient.
We were able to successfully complete testing on samples from 127 women. Among these, six mutations were identified (four in BRCA1 and two in BRCA2) representing 4.7% of the total or 9.5% of cases diagnosed before age forty. None of the mutation carriers had a family history of breast or ovarian cancer. Three of the four BRCA1 mutations were in exon 20: two were a G5331A mutation and the third was a 3.2 kb deletion. The fourth BRCA1 mutation was the 3819delGTAAA in exon 11. The two BRCA2 mutations were in exon 11 (3782del10 and 4512insT).
The G5331A mutation in BRCA1 appears to be a founder mutation in the Greek population.
BRCA1或BRCA2基因发生突变导致的乳腺癌约占所有乳腺癌病例的5%，但因国家而异。在希腊，对BRCA基因突变对乳腺癌发病率的贡献的研究大多受到样本量小以及使用因家族癌症病史而选择的病例的限制。本研究的目的是估计无家族病史的乳腺癌患者中BRCA基因突变的频率。
为此，我们招募了127名来自希腊雅典亚历山德拉医院（该市一家大型公立医院）的无家族病史的乳腺癌女性患者。使用多种技术组合检测BRCA1和BRCA2基因的突变，并通过直接测序进行确认。使用突变特异性检测方法寻找两个大的基因组缺失。从每位患者那里获取详细的癌症家族病史。
我们成功完成了对127名女性样本的检测。其中，鉴定出6个突变（4个在BRCA1基因中，2个在BRCA2基因中），占总数的4.7%，或40岁前确诊病例的9.5%。没有一个突变携带者有乳腺癌或卵巢癌家族病史。4个BRCA1基因突变中有3个在外显子20中：2个是G5331A突变，第3个是3.2 kb缺失。第4个BRCA1基因突变是外显子11中的3819delGTAAA。2个BRCA2基因突变在外显子11中（3782del10和4512insT）。
BRCA1基因中的G5331A突变似乎是希腊人群中的一个始祖突变。
