Bonaïti-Pellié C, Andrieu N, Arveux P, Bonadona V, Buecher B, Delpech M, Jolly D, Julian-Reynier C, Luporsi E, Noguès C, Nowak F, Olschwang S, Orsi F, Pujol P, Saurin J-C, Sinilnikova O, Stoppa-Lyonnet D, Thépot F
Inserm, U535, Villejuif, France.
Bull Cancer. 2009 Sep;96(9):875-900. doi: 10.1684/bdc.2009.0943.
Organised since 1990 in France, cancer genetics has been strengthened since 2003 by the programme "Plan Cancer" which resulted in an improvement of the organisation of activities. The aim of this review is to present an update of the estimation of the needs of the population in this field for the next ten years, provided by a group of experts mandated by the French National Cancer Institute. Identification and management of major hereditary predispositions to cancer have a major impact on decrease in mortality and incidence. Sensitivity of criteria for the detection of BRCA1/2 mutations could be substantially improved by enlarging the indication for genetic testing to isolated cases of ovarian cancer occurring before 70 years and to familial cases occurring after this age limit. In the Lynch syndrome, the present criteria would have an excellent sensitivity for the detection of mutations in the mismatch repair (MMR) genes if the pre-screening of tumours on microsatellite instability (MSI) phenotype was effective, but these criteria are actually poorly applied. However, genetic testing should not be proposed to all the patients affected by tumours belonging to the spectrum of major predispositions and a fortiori to unaffected persons unless an affected relative has been identified as a carrier. The prescription of tests should continue to be strictly controlled and organised, in patients as well as in at-risk relatives. The enlargement of criteria and the improvement in the spreading of recommendations should result in an increase of genetic counselling activity and of the prescriptions of tests by a factor 2 to 4, and to a lesser extent in the clinical management of at risk persons. In a near future, it appears important to mandate experts on specific issues such as the determinants of the lack of effective application of tumour screening for MSI phenotype, the recommendations for the identification and the management of MYH-associated polyposis, or the predictive value of tumour characteristics for the identification of BRCA1/2 mutations. The expected increase in cancer genetics activity will need an optimal organisation to increase the throughput. Such measures will help in facing up to new predispositions that will probably be identified in common cancers.
癌症遗传学自1990年起在法国开展组织工作，自2003年起通过“癌症计划”项目得到加强，该项目使活动组织得到改善。本综述的目的是介绍由法国国家癌症研究所委托的一组专家提供的对该领域未来十年人群需求估计的最新情况。癌症主要遗传易感性的识别和管理对降低死亡率和发病率有重大影响。通过将基因检测的指征扩大到70岁之前发生的孤立性卵巢癌病例以及该年龄限制之后发生的家族性病例，可大幅提高检测BRCA1/2突变标准的敏感性。在林奇综合征中，如果对微卫星不稳定性（MSI）表型的肿瘤进行预筛查有效，那么目前的标准对检测错配修复（MMR）基因突变将具有出色的敏感性，但实际上这些标准应用不佳。然而，除非已确定有患病亲属为携带者，否则不应向所有受主要易感性范围内肿瘤影响的患者，更不应向未患病者提议进行基因检测。检测的开具应继续在患者及其高危亲属中受到严格控制和组织。标准的扩大以及建议传播的改善应会使遗传咨询活动和检测开具增加2至4倍，对高危人群的临床管理影响较小。在不久的将来，指定专家处理特定问题似乎很重要，例如MSI表型肿瘤筛查缺乏有效应用的决定因素、MYH相关息肉病的识别和管理建议，或肿瘤特征对BRCA1/2突变识别的预测价值。癌症遗传学活动预期的增加将需要优化组织以提高通量。这些措施将有助于应对可能在常见癌症中发现的新的易感性。
