Defining Early-Onset Kidney Cancer: Implications for Germline and Somatic Mutation Testing and Clinical Management
Defining Early-Onset Kidney Cancer: Implications for Germline and Somatic Mutation Testing and Clinical Management
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DOI：
10.1200/jco.2013.50.8192
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发表时间：
2014-02-10
影响因子：
45.3
通讯作者：
Linehan, W. Marston
中科院分区：
文献类型：
--
作者：
Shuch, Brian;Vourganti, Srinivas;Linehan, W. Marston
目的大约5%~8%的肾细胞癌(RCC)是遗传性的。对于肾癌胚系突变检测的患者选择，目前尚无指南。我们评估发病年龄如何表明需要进行胚系突变检测来检测遗传性肾癌。患者和方法我们分析了SEER-17计划和我们机构遗传性肾癌人群中肾癌病例的年龄分布。年龄分布按性别、种族、组织学和遗传性癌症综合征进行比较。结果SEER-17中肾癌患者的平均年龄为岁，其分布接近正态分布。按种族、性别和亚型观察到统计学差异(P<；0.05)。最低年龄为46岁，性别、种族和组织学略有不同。608例遗传性肾癌患者的平均发病年龄为39.3岁，中位发病年龄为37岁。虽然年龄因具体症状而异，但其中70%的病例被发现处于或低于最低年龄。基于年龄的基因检测阈值建模表明，第10个百分位数的敏感度和特异度最高。结论发病年龄较早可能是遗传性肾癌的一个标志。即使在没有临床表现和个人/家族史的情况下，46岁或以下的发病年龄也应引发遗传咨询/生殖系突变检测的考虑，并可作为建立基因检测指南时有用的截止点。(C)美国临床肿瘤学会2013年
Purpose Approximately 5% to 8% of renal cell carcinoma (RCC) is hereditary. No guidelines exist for patient selection for RCC germline mutation testing. We evaluate how age of onset could indicate the need for germline mutation testing for detection of inherited forms of kidney cancer.Patients and Methods We analyzed the age distribution of RCC cases in the SEER-17 program and in our institutional hereditary kidney cancer population. The age distributions were compared by sex, race, histology, and hereditary cancer syndrome. Models were established to evaluate the specific age thresholds for genetic testing.Results The median age of patients with RCC in SEER-17 was 64 years, with the distribution closely approaching normalcy. Statistical differences were observed by race, sex, and subtype (P < .05). The bottom decile cutoff was 46 years of age and slightly differed by sex, race, and histology. The mean and median ages at presentation of 608 patients with hereditary kidney cancer were 39.3 years and 37 years, respectively. Although age varied by specific syndrome, 70% of these cases were found to lie at or below the bottom age decile. Modeling age-based genetic testing thresholds demonstrated that the 10th percentile maximized sensitivity and specificity.Conclusion Early age of onset might be a sign of hereditary RCC. Even in the absence of clinical manifestations and personal/family history, an age of onset of 46 years or younger should trigger consideration for genetic counseling/germline mutation testing and may serve as a useful cutoff when establishing genetic testing guidelines. (C) 2013 by American Society of Clinical Oncology