Schiavi A, Lavigne J, Turcotte R, Kasprzak L, Dumas N, Chong G, Freeman C, Alameldin M, Galiatsatos P, Palma L, Foulkes W D
Department of Medical Genetics, McGill University Health Centre, McGill University, Montreal, QC;
Department of Surgery, McGill University, Montreal, QC;
Curr Oncol. 2015 Oct;22(5):317-25. doi: 10.3747/co.22.2588.
Sarcomas in adults can be associated with hereditary cancer syndromes characterized by early-onset predisposition to numerous types of cancer. Because of variability in familial presentation and the largely unexplained genetic basis of sarcomas, ascertainment of patients for whom a genetics evaluation is most indicated poses challenges. We assessed the utility of a Sarcoma Clinic Genetic Screening (scgs) questionnaire in facilitating that task.
Between 2008 and 2012, 169 patients (median age: 53 years; range: 17-88 years) completed a self-administered scgs questionnaire. A retrospective chart review was completed for all respondents, and descriptive statistics were reported. Probands were divided into two groups depending on whether they did or did not report a family history of Li-Fraumeni syndrome-type cancers.
A family history of cancer (as far as 3rd-degree relatives) was reported in 113 of 163 sarcoma patients (69%). Eeles Li-Fraumeni-like (lfl) criteria were fulfilled in 46 probands (28%), Chompret lfl in 21 (13%), Birch lfl in 8 (5%), and classic Li-Fraumeni in none. In the 10 probands tested for TP53 mutations, 1 pathogenic mutation was found. Further investigation of selected families led to the discovery of germline mutations in MLH1, MSH2, and APC genes in 3 individuals.
The scgs questionnaire was useful for ascertaining probands with sarcoma who could benefit from a genetic assessment. The tool allowed us to identify high-risk families fitting the criteria for lfl and, surprisingly, other hereditary cancer syndromes. Similar questionnaires could be used in other cancer-specific clinics to increase awareness of the genetic component of these cancers.
成人肉瘤可能与遗传性癌症综合征相关，其特征为早发性易患多种类型癌症。由于家族表现的变异性以及肉瘤在很大程度上尚未明确的遗传基础，确定最适合进行遗传学评估的患者具有挑战性。我们评估了肉瘤诊所基因筛查（scgs）问卷在协助这项任务中的效用。
2008年至2012年期间，169名患者（中位年龄：53岁；范围：17 - 88岁）完成了一份自我填写的scgs问卷。对所有受访者进行了回顾性病历审查，并报告了描述性统计数据。根据先证者是否报告有李-弗劳梅尼综合征型癌症的家族史，将其分为两组。
163名肉瘤患者中有113名（69%）报告有癌症家族史（追溯至三级亲属）。46名先证者（28%）符合伊尔斯李-弗劳梅尼样（lfl）标准，21名（13%）符合乔普雷lfl标准，8名（5%）符合伯奇lfl标准，无一例符合经典李-弗劳梅尼标准。在检测TP53突变的10名先证者中，发现1个致病突变。对选定家族的进一步调查发现3名个体的MLH1、MSH2和APC基因存在种系突变。
scgs问卷有助于确定可能从遗传学评估中受益的肉瘤先证者。该工具使我们能够识别符合lfl标准的高危家族，令人惊讶的是，还能识别其他遗传性癌症综合征。类似的问卷可用于其他癌症专科诊所，以提高对这些癌症遗传成分的认识。
