PDF(Pubmed)
Abstract：
Current National Comprehensive Cancer Network ® (NCCN ®) guidelines for Colorectal Genetic/Familial High-Risk Assessment provide limited guidance for genetic testing for individuals with already diagnosed hereditary cancer conditions. We are presenting the case of a 36-year-old woman who was diagnosed with Lynch Syndrome at age 23 after genetic testing for a familial variant (c.283del) in the MLH1 gene. The patient had a previous history of Hodgkin Lymphoma at the time of familial variant testing, and she would later develop stage IIIa cecal adenocarcinoma at age 33 and metastatic papillary thyroid carcinoma at age 35. The patient\'s family history included a first-degree relative who was diagnosed with colorectal cancer at age 39, multiple second-degree relatives with colorectal, endometrial, and stomach cancer, and third and fourth-degree relatives with breast cancer. In light of her personal and family history, a comprehensive cancer panel was recommended. This panel found a second hereditary cancer predisposition syndrome: a likely pathogenic variant (c. 349 A > G) in the CHEK2 gene. This specific CHEK2 variant was recently reported to confer a moderately increased risk for breast cancer. The discovery of this second cancer predisposition syndrome had important implications for the patient\'s screening and risk management. While uncommon, the possibility of an individual having multiple cancer predisposition syndromes is important to consider when evaluating patients and families for hereditary cancer, even when a familial variant has been identified.
摘要：
当前的国家综合癌症网络®（NCCN®）结肠直肠遗传/家族高风险评估指南为已经诊断出遗传性癌症疾病的个体提供了有限的遗传检测指导。我们正在介绍一名36岁妇女的病例，该妇女在遗传检测MLH1基因中的家族性变异（c.283del）后，在23岁时被诊断出患有林奇综合症。患者在进行家族性变异检测时曾有霍奇金淋巴瘤病史，她后来在33岁时发展为IIIa期盲肠腺癌，在35岁时发展为转移性甲状腺乳头状癌。患者的家族史包括一个在39岁时被诊断为结直肠癌的一级亲属，多个结直肠癌二级亲属，子宫内膜,和胃癌，以及患有乳腺癌的三级和四级亲属。鉴于她的个人和家族史，推荐了一个全面的癌症小组.该小组发现了第二种遗传性癌症易感性综合征：可能的致病变体（c。349A>G）在CHEK2基因中。最近据报道，这种特定的CHEK2变体使乳腺癌的风险适度增加。这种第二种癌症易感性综合征的发现对患者的筛查和风险管理具有重要意义。虽然不常见，在评估遗传性癌症的患者和家庭时，必须考虑具有多种癌症易感性综合征的个体的可能性，即使已经确定了家族变异。
