Hartwig Martyna, Janiszewska Hanna, Bąk Aneta, Pilarska Maria, Heise Marta, Junkiert-Czarnecka Anna, Laskowski Ryszard, Haus Olga
Department of Clinical Genetics, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
Contemp Oncol (Pozn). 2013;17(1):34-7. doi: 10.5114/wo.2013.33767. Epub 2013 Mar 15.
Germline mutations in BRCA tumor suppressor genes are strongly associated with breast and ovarian cancer. The lifetime risk of these cancers in women with BRCA1 mutation is 84% and 27%, respectively. Studies on the prevalence of BRCA1 c.68_69delAG congenital mutation, the most frequent in Ashkenazi Jews, among women with breast cancer from north-central Poland and review of the literature on other regions of the country. Evaluation of the c.68_69delAG association with breast cancer risk, with respect to women's age at diagnosis and family history of cancer.
252 women with breast cancer, without any of the mutations c.5266dupC, c.181T > G, or c.4034delA, regardless of histological type and family history of cancer. The mutation was detected using allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) assay and confirmed by sequence analysis.
The c.68_69delAG mutation was disclosed in one out of the 252 women (0.4%), who had been diagnosed with breast cancer at age 43. Family investigations revealed the presence of c.68_69delAG also in the patient's mother, diagnosed with breast cancer at age 68. Sequence analysis confirmed the heterozygous status of the mutation, and family investigation its hereditary character. In the group of families with breast cancer history 1.4% frequency of c.68_69delAG was shown.
Among families with breast cancer aggregation, originating from north-central Poland, c.68_69delAG is a rare BRCA1 alteration, similarly to other central regions of the country, investigated by other authors. However, in northern, north-western and south-western parts of Poland, it occurs 2-4 times more frequently than in our region.
BRCA肿瘤抑制基因的种系突变与乳腺癌和卵巢癌密切相关。携带BRCA1突变的女性患这些癌症的终生风险分别为84%和27%。本研究旨在调查波兰中北部乳腺癌女性中最常见于德系犹太人的BRCA1基因c.68_69delAG先天性突变的患病率，并回顾该国其他地区的相关文献。评估c.68_69delAG与乳腺癌风险的关联，包括女性诊断时的年龄和癌症家族史。
选取252例乳腺癌女性患者，她们均未携带c.5266dupC、c.181T>G或c.4034delA突变，不考虑组织学类型和癌症家族史。采用等位基因特异性寡核苷酸聚合酶链反应（ASO-PCR）检测突变，并通过序列分析进行确认。
252例女性中有1例（0.4%）检测到c.68_69delAG突变，该患者43岁时被诊断为乳腺癌。家族调查显示，患者68岁的母亲也携带c.68_69delAG突变，被诊断为乳腺癌。序列分析证实了该突变的杂合状态，家族调查证实了其遗传性。在有乳腺癌家族史的人群中，c.68_69delAG的频率为1.4%。
在波兰中北部有乳腺癌聚集现象的家族中，c.68_69delAG是一种罕见的BRCA1基因改变，与该国其他中心地区的情况类似，其他作者也有相关研究。然而，在波兰的北部、西北部和西南部，该突变的发生频率比我们所在地区高2至4倍。
