新的基底细胞癌易感基因座。
New basal cell carcinoma susceptibility loci.
作者信息
Stacey Simon N, Helgason Hannes, Gudjonsson Sigurjon A, Thorleifsson Gudmar, Zink Florian, Sigurdsson Asgeir, Kehr Birte, Gudmundsson Julius, Sulem Patrick, Sigurgeirsson Bardur, Benediktsdottir Kristrun R, Thorisdottir Kristin, Ragnarsson Rafn, Fuentelsaz Victoria, Corredera Cristina, Gilaberte Yolanda, Grasa Matilde, Planelles Dolores, Sanmartin Onofre, Rudnai Peter, Gurzau Eugene, Koppova Kvetoslava, Nexø Bjørn A, Tjønneland Anne, Overvad Kim, Jonasson Jon G, Tryggvadottir Laufey, Johannsdottir Hrefna, Kristinsdottir Anna M, Stefansson Hreinn, Masson Gisli, Magnusson Olafur T, Halldorsson Bjarni V, Kong Augustine, Rafnar Thorunn, Thorsteinsdottir Unnur, Vogel Ulla, Kumar Rajiv, Nagore Eduardo, Mayordomo José I, Gudbjartsson Daniel F, Olafsson Jon H, Stefansson Kari
机构信息
deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
1] Landspitali-University Hospital, Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
出版信息
Nat Commun. 2015 Apr 9;6:6825. doi: 10.1038/ncomms7825.
In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10(-12)), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10(-9)), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10(-12)) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10(-16)). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained.
在一项针对赋予皮肤基底细胞癌（BCC）风险的DNA序列变异的正在进行的筛查中，我们对通过对2636名冰岛人进行全基因组测序检测到并推算到4572例BCC患者和266358名对照中的24988228个单核苷酸多态性（SNP）和小插入缺失进行了全基因组关联研究（GWAS）。在此，我们展示了四个新的BCC易感位点的发现：2p24上的MYCN（rs57244888[C]，比值比（OR）=0.76，P=4.7×10⁻¹²）、2q33上的CASP8-ALS2CR12（rs13014235[C]，OR=1.15，P=1.5×10⁻⁹）、8q21上的ZFHX4（rs28727938[G]，OR=0.70，P=3.5×10⁻¹²）和10p14上的GATA3（rs73635312[A]，OR=0.74，P=2.4×10⁻¹⁶）。精细定位显示，与rs73635312[A]相关的两个变异出现在GATA3转录因子的保守结合位点中。此外，表达微阵列和RNA测序表明，rs13014235[C]和一个相关的SNP rs700635[C]与CASP8剪接变异体的表达相关，其中内含子8的序列被保留。
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