New basal cell carcinoma susceptibility loci.

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.

Citation

Simon N Stacey, Hannes Helgason, Sigurjon A Gudjonsson, Gudmar Thorleifsson, Florian Zink, Asgeir Sigurdsson, Birte Kehr, Julius Gudmundsson, Patrick Sulem, Bardur Sigurgeirsson, Kristrun R Benediktsdottir, Kristin Thorisdottir, Rafn Ragnarsson, Victoria Fuentelsaz, Cristina Corredera, Yolanda Gilaberte, Matilde Grasa, Dolores Planelles, Onofre Sanmartin, Peter Rudnai, Eugene Gurzau, Kvetoslava Koppova, Bjørn A Nexø, Anne Tjønneland, Kim Overvad, Jon G Jonasson, Laufey Tryggvadottir, Hrefna Johannsdottir, Anna M Kristinsdottir, Hreinn Stefansson, Gisli Masson, Olafur T Magnusson, Bjarni V Halldorsson, Augustine Kong, Thorunn Rafnar, Unnur Thorsteinsdottir, Ulla Vogel, Rajiv Kumar, Eduardo Nagore, José I Mayordomo, Daniel F Gudbjartsson, Jon H Olafsson, Kari Stefansson. New basal cell carcinoma susceptibility loci. Nature communications. 2015 Apr 09;6:6825

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PMID: 25855136

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