Lynch Henry T, Fusaro Ramon M, Lynch Jane F
Department of Preventive Medicine, Creighton University School of Medicine, Omaha NE 68178, USA.
Future Oncol. 2007 Apr;3(2):169-81. doi: 10.2217/14796694.3.2.169.
Oncologists who are aware of the progress in hereditary cancer syndrome diagnosis, and, in particular, of how this effort may be effectively facilitated through a comprehensive family history in concert with molecular genetic studies, are in the envious position of designing highly targeted screening and management programs for the membership of these cancer-prone families. The Lynch syndrome is discussed as a clinical model wherein the presence of mismatch repair mutations provides a high level of diagnostic certainty for the initiation of targeted cancer screening and management. The familial atypical multiple mole melanoma-pancreatic cancer (FAMMM-PC) syndrome, on the other hand, provides another model with cancer-control potential. Given its phenotypic features of multiple atypical nevi, high total body mole count and cutaneous malignant melanoma, coupled with the integral association of PC in a subset of FAMMM kindreds with the CDKN2A germline mutation, this may result in a perhaps lower level of diagnostic certainty when compared with the Lynch syndrome. This knowledge may impact upon progress in the earlier diagnosis of melanoma and provide an impetus for creative diagnostic methods in PC, a disease that, at this time, demonstrates a mortality rate virtually identical to its incidence rate.
了解遗传性癌症综合征诊断进展,尤其是知晓如何通过全面家族史结合分子遗传学研究有效推动这一工作的肿瘤学家,处于有利地位,能够为这些易患癌症家族的成员设计高度针对性的筛查和管理方案。文中将林奇综合征作为一种临床模型进行讨论,其中错配修复突变的存在为启动针对性癌症筛查和管理提供了高度的诊断确定性。另一方面,家族性非典型多发性痣黑色素瘤-胰腺癌(FAMMM-PC)综合征提供了另一个具有癌症控制潜力的模型。鉴于其具有多个非典型痣、全身痣总数较多和皮肤恶性黑色素瘤的表型特征,再加上一部分携带CDKN2A种系突变的FAMMM家族中存在胰腺癌,与林奇综合征相比,这可能导致诊断确定性水平较低。这一认知可能会影响黑色素瘤早期诊断的进展,并为胰腺癌的创新性诊断方法提供动力,目前胰腺癌的死亡率几乎与其发病率相同。