Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology, University of Brescia, 25123 Brescia, Italy.
Oncol Rep. 2010 Dec;24(6):1661-7. doi: 10.3892/or_00001031.
Hereditary breast cancer accounts for 5-10% of all cases of breast cancer and 10-15% of ovarian cancer and is characterised by dominant inheritance, early onset, the severity of the disease and bilaterality. About 30% of cases with hereditary breast and ovarian cancer have mutations in the BRCA1 and BRCA2 genes. Women with a mutation in the BRCA1 gene have a 80-90% lifetime risk of developing breast cancer, and 40-65% chance of developing ovarian cancer. Most studies carried out throughout the world indicate that the prevalence of BRCA1 and BRCA2 mutation is lower than originally suggested by early studies on large families with several affected members. Studies performed in Italy have reported different prevalence of BRCA1 and BRCA2 mutations, probably due to different selection criteria and to the variability of the techniques used. In this study, we performed a screening of BRCA1 and BRCA2 in families from northern Italy with familial recurrence of breast cancer or ovarian cancer in which the individual risk of patients of being carriers of BRCA1 and BRCA2 mutation was evaluated using BRCAPRO (CAGene) software. We enrolled 27 patients of 101 unrelated families selected when they fulfilled the inclusion criteria of the American Society of Clinical Oncology (ASCO). Specific risk evaluation, genetic test administration if needed, and discussion of the results were offered during multi-disciplinary genetic, surgical and psychological counselling. Seven probands (35%) found BRCA1/2 sequence variation carriers; no BRCA1 and BRCA2 mutations were detected in the remaining 13 probands. Two (15%) patients had BRCA1 mutations and 5 (25%) patients had BRCA2 mutations. In the latter case, BRCA2 delA 9158fs+29stop mutation in exon 22, never previously described and a new sequence variation (T703N) in exon 11 were identified.
遗传性乳腺癌占所有乳腺癌病例的 5-10%，占卵巢癌的 10-15%，其特征为显性遗传、发病早、疾病严重程度和双侧性。约 30%的遗传性乳腺癌和卵巢癌患者存在 BRCA1 和 BRCA2 基因突变。BRCA1 基因突变的女性一生中患乳腺癌的风险为 80-90%，患卵巢癌的风险为 40-65%。全世界大多数研究表明，BRCA1 和 BRCA2 基因突变的流行率低于早期对有多个受影响成员的大家族进行的研究最初提出的水平。在意大利进行的研究报告了 BRCA1 和 BRCA2 突变的不同流行率，这可能是由于不同的选择标准和使用的技术的可变性。在这项研究中，我们对来自意大利北部的具有乳腺癌或卵巢癌家族性复发的家庭进行了 BRCA1 和 BRCA2 的筛查，使用 BRCAPRO（CAGene）软件评估了患者个体携带 BRCA1 和 BRCA2 突变的风险。我们招募了 27 名患者，这些患者来自 101 个无关家庭，这些家庭在满足美国临床肿瘤学会（ASCO）的纳入标准时被选中。在多学科遗传、手术和心理辅导中提供了特定的风险评估、遗传测试管理（如果需要）和结果讨论。7 名先证者（35%）发现了 BRCA1/2 序列变异携带者；其余 13 名先证者未检测到 BRCA1 和 BRCA2 突变。2 名（15%）患者存在 BRCA1 突变，5 名（25%）患者存在 BRCA2 突变。在后一种情况下，确定了从未描述过的外显子 22 中的 BRCA2 delA 9158fs+29stop 突变和外显子 11 中的新序列变异（T703N）。
