Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
Breast Cancer Res Treat. 2013 Aug;141(1):135-44. doi: 10.1007/s10549-013-2669-9. Epub 2013 Aug 24.
Based on nationwide data from the French national cancer institute (INCa), we analyzed the evolution of cancer genetics consultations and testing over time, and the uptake of targeted tests in relatives of families with BRCA1/2 or MMR genes mutation. Genetic testing and consultations for familial high-risk individuals are exclusively funded and monitored by the INCa in France. All nationwide cancer genetics centers reported annually standardized parameters of activity from 2003 to 2011. The analysis included a total of 240,134 consultations and 134,652 genetic tests enabling to identify 32,494 mutation carriers. Referral for hereditary breast and ovarian cancer (HBOC) or colorectal cancer predisposition syndromes represented 59 % (141,639) and 23.2 % (55,698) consultations, respectively. From 2003 to 2011, we found a dramatic and steady increase of tests performed for BRCA1/2 (from 2,095 to 7,393 tests/year, P < 0.0001) but not for MMR genes (from 1,144 to 1,635/year, P = NS). The overall percentage of deleterious mutations identified in the probands tested was 13.8 and 20.9 % in HBOC and Lynch syndromes, respectively. Pooled analysis for BRCA1/2 and Lynch syndrome tests showed an inverse relationship between the percentage of mutation detected and the absolute number of tests performed over the time (overall Cochran-Armitage test for trend: P < 0.001). In families with BRCA1/2 or MMR identified mutations, there was an average number of 2.94 and 3.28 relatives performing targeted tests, respectively. This nationwide study shows a lack of referral and genetic testing in Lynch as compared to HBOC syndromes. Only a third of relatives of a proband with a predisposing mutation performed a targeted test. Enhanced information about benefit of genetic testing should be given to clinicians and patients for Lynch syndrome and relatives of a proband carrying an identified predisposing mutation.
基于法国国家癌症研究所（INCa）的全国性数据，我们分析了癌症遗传学咨询和检测随时间的演变，以及在 BRCA1/2 或 MMR 基因突变家族的亲属中进行靶向检测的情况。法国的 INCa 独家资助和监测家族高危人群的基因检测和咨询。所有全国性癌症遗传学中心每年都报告 2003 年至 2011 年的标准化活动参数。该分析共包括 240134 次咨询和 134652 次基因检测，可确定 32494 名突变携带者。遗传性乳腺癌和卵巢癌（HBOC）或结直肠癌易感性综合征的转诊分别占 59%（141639 次）和 23.2%（55698 次）的咨询。从 2003 年到 2011 年，我们发现 BRCA1/2 检测的数量急剧且稳定增加（从每年 2095 次增加到 7393 次，P <0.0001），而 MMR 基因检测的数量没有增加（从每年 1144 次增加到 1635 次，P=NS）。在接受检测的先证者中，确定的有害突变的总体百分比分别为 HBOC 和林奇综合征中的 13.8%和 20.9%。BRCA1/2 和林奇综合征检测的汇总分析显示，随着时间的推移，检测到的突变百分比与进行的检测数量之间存在反比关系（总体 Cochran-Armitage 趋势检验：P<0.001）。在确定 BRCA1/2 或 MMR 基因突变的家族中，分别有 2.94 名和 3.28 名亲属进行了靶向检测。这项全国性研究表明，与 HBOC 综合征相比，林奇综合征的转诊和基因检测不足。只有三分之一的先证者携带易感性突变的亲属进行了靶向检测。应向临床医生和患者提供关于林奇综合征和携带已确定易感性突变的先证者亲属的基因检测益处的更多信息。
