Ewald Ingrid P, Izetti Patrícia, Vargas Fernando R, Moreira Miguel Am, Moreira Aline S, Moreira-Filho Carlos A, Cunha Danielle R, Hamaguchi Sara, Camey Suzi A, Schmidt Aishameriane, Caleffi Maira, Koehler-Santos Patrícia, Giugliani Roberto, Ashton-Prolla Patricia
Laboratório de Medicina Genômica, Centro de Pesquisa Experimental - Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90035-903, Porto Alegre, RS, Brazil.
Hered Cancer Clin Pract. 2011 Dec 20;9(1):12. doi: 10.1186/1897-4287-9-12.
About 5-10% of breast and ovarian carcinomas are hereditary and most of these result from germline mutations in the BRCA1 and BRCA2 genes. In women of Ashkenazi Jewish ascendance, up to 30% of breast and ovarian carcinomas may be attributable to mutations in these genes, where 3 founder mutations, c.68_69del (185delAG) and c.5266dup (5382insC) in BRCA1 and c.5946del (6174delT) in BRCA2, are commonly encountered. It has been suggested by some authors that screening for founder mutations should be undertaken in all Brazilian women with breast cancer. Thus, the goal of this study was to determine the prevalence of three founder mutations, commonly identified in Ashkenazi individuals in a sample of non-Ashkenazi cancer-affected Brazilian women with clearly defined risk factors for hereditary breast and ovarian cancer (HBOC) syndrome. Among 137 unrelated Brazilian women from HBOC families, the BRCA1c.5266dup mutation was identified in seven individuals (5%). This prevalence is similar to that encountered in non-Ashkenazi HBOC families in other populations. However, among patients with bilateral breast cancer, the frequency of c.5266dup was significantly higher when compared to patients with unilateral breast tumors (12.1% vs 1.2%, p = 0.023). The BRCA1 c.68_69del and BRCA2 c.5946del mutations did not occur in this sample. We conclude that screening non-Ashkenazi breast cancer-affected women from the ethnically heterogeneous Brazilian populations for the BRCA1 c.68_69del and BRCA2 c.5946del is not justified, and that screening for BRCA1c.5266dup should be considered in high risk patients, given its prevalence as a single mutation. In high-risk patients, a negative screening result should always be followed by comprehensive BRCA gene testing. The finding of a significantly higher frequency of BRCA1 c.5266dup in women with bilateral breast cancer, as well as existence of other as yet unidentified founder mutations in this population, should be further assessed in a larger well characterized high-risk cohort.
约5%-10%的乳腺癌和卵巢癌具有遗传性，其中大多数是由BRCA1和BRCA2基因的种系突变引起的。在阿什肯纳兹犹太裔女性中，高达30%的乳腺癌和卵巢癌可能归因于这些基因的突变，其中常见3种奠基者突变，即BRCA1基因中的c.68_69del（185delAG）和c.5266dup（5382insC）以及BRCA2基因中的c.5946del（6174delT）。一些作者建议，所有患乳腺癌的巴西女性都应进行奠基者突变筛查。因此，本研究的目的是确定在有明确遗传性乳腺癌和卵巢癌（HBOC）综合征风险因素的非阿什肯纳兹裔巴西癌症患者样本中，阿什肯纳兹人常见的3种奠基者突变的患病率。在137名来自HBOC家族的不相关巴西女性中，有7人（5%）检测到BRCA1基因的c.5266dup突变。这一患病率与其他人群中非阿什肯纳兹裔HBOC家族的患病率相似。然而，在双侧乳腺癌患者中，c.5266dup的频率显著高于单侧乳腺肿瘤患者（12.1%对1.2%，p = 0.023）。本样本中未出现BRCA1基因的c.68_69del和BRCA2基因的c.5946del突变。我们得出结论，对来自种族异质的巴西人群的非阿什肯纳兹裔乳腺癌患者进行BRCA1基因的c.68_69del和BRCA2基因的c.5946del筛查是不合理的，鉴于BRCA1基因的c.5266dup作为单一突变的患病率，应考虑对高危患者进行该突变的筛查。在高危患者中，筛查结果为阴性后应始终进行全面的BRCA基因检测。BRCA1基因的c.5266dup在双侧乳腺癌女性中的频率显著更高这一发现，以及该人群中存在其他尚未确定的奠基者突变，应在更大规模、特征明确的高危队列中进一步评估。
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