Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype.
Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype.
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成人的家族性睾丸生殖细胞肿瘤：2010年遗传危险因素和临床表型的摘要。
DOI：
10.1677/erc-09-0254
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发表时间：
2010-06
影响因子：
3.9
通讯作者：
Korde LA
中科院分区：
文献类型：
--
作者：
Greene MH;Kratz CP;Mai PL;Mueller C;Peters JA;Bratslavsky G;Ling A;Choyke PM;Premkumar A;Bracci J;Watkins RJ;McMaster ML;Korde LA
睾丸生殖细胞肿瘤 (FTGCT) 的家族聚集性已得到充分描述，表明存在遗传性 TGCT 亚群。大约 1.4% 的新诊断 TGCT 患者报告有 TGCT 阳性家族史。 TGCT 患者的儿子和兄弟姐妹的 TGCT 风险分别增加四到六倍和八到十倍。分离分析提示常染色体隐性遗传模式。尽管尚未绘制出高外显率癌症易感性基因的图谱，但连锁分析已经确定了几个具有一定意义的基因组区域。这些数据表明，多个常见等位基因的综合影响（每个等位基因都具有适度的风险）可能是家族性睾丸癌的基础。家庭表现出轻微的表型：受影响的家庭最常见的数量是 2 个。与散发病例相比，家族病例的诊断年龄要小 2-3 岁。家族性精原细胞瘤与非精原细胞瘤的比率为1.0。 FTGCT 比散发性 TGCT 更可能是双侧的。这种综合征是癌症部位特异性的。睾丸微石症是新近认识的 FTGCT 组成部分。候选基因关联研究表明 Y 染色体 gr/gr 缺失和 PDE11A 基因突变是 FTGCT 风险的遗传修饰因素。两项全基因组关联研究主要针对散发性但也有家族性的 TGCT 病例，表明 KIT 配体、SPRY4 和 BAK1 基因是 TGCT 风险调节因子。所有五个基因座都与正常睾丸发育和/或男性不育有关。这些遗传数据为 FTGCT 的遗传基础提供了新的见解，并为未来的 TGCT 研究提供了宝贵的指导。
Familial aggregations of testicular germ cell tumor (FTGCT) have been well described, suggesting the existence of a hereditary TGCT subset. Approximately 1.4% of newly diagnosed TGCT patients report a positive family history of TGCT. Sons and siblings of TGCT patients have four- to sixfold and eight- to tenfold increases in TGCT risk respectively. Segregation analyses suggest an autosomal recessive mode of inheritance. Linkage analyses have identified several genomic regions of modest interest, although no high-penetrance cancer susceptibility gene has been mapped yet. These data suggest that the combined effects of multiple common alleles, each conferring modest risk, might underlie familial testicular cancer. Families display a mild phenotype: the most common number of affected families is 2. Age at diagnosis is 2–3 years younger for familial versus sporadic cases. The ratio of familial seminoma to nonseminoma is 1.0. FTGCT is more likely to be bilateral than sporadic TGCT. This syndrome is cancer site specific. Testicular microlithiasis is a newly recognized FTGCT component. Candidate gene-association studies have implicated the Y chromosome gr/gr deletion and PDE11A gene mutations as genetic modifiers of FTGCT risk. Two genomewide association studies of predominantly sporadic but also familial cases of TGCT have implicated the KIT-ligand, SPRY4, and BAK1 genes as TGCT risk modifiers. All five loci are involved in normal testicular development and/or male infertility. These genetic data provide a novel insight into the genetic basis of FTGCT, and an invaluable guide to future TGCT research.