Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23
Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23
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DOI：
10.1093/hmg/ddt109
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发表时间：
2013-07-01
影响因子：
3.5
通讯作者：
McGlynn, Katherine A.
中科院分区：
文献类型：
--
作者：
Schumacher, Fredrick R.;Wang, Zhaoming;McGlynn, Katherine A.
全基因组关联研究（GWAS）已经确定了与睾丸生殖细胞肿瘤（TGCT）风险增加相关的多种常见遗传变异。先前的GWAS报告了UCK 2基因中染色体1 q23上可能的TGCT易感性位点，但在复制后未能达到全基因组意义。我们通过对两个独立的GWAS进行荟萃分析，包括940例TGCT病例和1559例对照，对染色体1 q23上的122个单核苷酸多态性（SNP）进行了询问，并对来自4项病例对照研究的另外2202例TGCT病例和2386例对照中最显著的SNP进行了随访。我们观察到几个UCK 2标记物的全基因组显著相关性，其中最显著的是rs3790665（P-组合6.0 10（9））。TGCT的独立家族研究提供了额外的支持，其中观察到rs3790665与TGCT风险的显著过度传播（P-FBAT 2.3 10（3））。在这里，我们为UCK 2遗传变异和TGCT风险之间的关联提供了大量证据。
Genome-wide association studies (GWASs) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCTs). A previous GWAS reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene, but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWASs including a total of 940 TGCT cases and 1559 controls for 122 single-nucleotide polymorphisms (SNPs) on chromosome 1q23 and followed up the most significant SNPs in an additional 2202 TGCT cases and 2386 controls from four casecontrol studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (P-Combined 6.0 10(9)). Additional support is provided from an independent familial study of TGCT where a significant over-transmission for rs3790665 with TGCT risk was observed (P-FBAT 2.3 10(3)). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk.