title: New basal cell carcinoma susceptibility loci.
abstract: 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.
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Simon N
authors: SN
authors: Stacey
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Hannes
authors: H
authors: Helgason
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Sigurjon A
authors: SA
authors: Gudjonsson
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Gudmar
authors: G
authors: Thorleifsson
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Florian
authors: F
authors: Zink
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Asgeir
authors: A
authors: Sigurdsson
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Birte
authors: B
authors: Kehr
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Julius
authors: J
authors: Gudmundsson
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Patrick
authors: P
authors: Sulem
authors: 1] Landspitali-University Hospital, Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
authors: Bardur
authors: B
authors: Sigurgeirsson
authors: 1] Landspitali-University Hospital, Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
authors: Kristrun R
authors: KR
authors: Benediktsdottir
authors: 1] Landspitali-University Hospital, Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
authors: Kristin
authors: K
authors: Thorisdottir
authors: 1] Landspitali-University Hospital, Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
authors: Rafn
authors: R
authors: Ragnarsson
authors: Division of Dermatology, Gregorio Marañón Hospital, Madrid 28007, Spain.
authors: Victoria
authors: V
authors: Fuentelsaz
authors: Division of Dermatology, Quiron Hospital, 50009 Zaragoza, Spain.
authors: Cristina
authors: C
authors: Corredera
authors: Division of Dermatology, San Jorge General Hospital, Huesca 22004, Spain.
authors: Yolanda
authors: Y
authors: Gilaberte
authors: Division of Dermatology, University Hospital, Zaragoza 50009, Spain.
authors: Matilde
authors: M
authors: Grasa
authors: Laboratory of Histocompatibility-Molecular Biology, Centro de Transfusión de la Comunidad Valenciana, Avenida del Cid, 65-A, Valencia 46014, Spain.
authors: Dolores
authors: D
authors: Planelles
authors: 1] Department of Oncology, Instituto Valenciano de Oncologia, Valencia 46009, Spain [2] Universidad Católica de Valencia, Valencia 46003, Spain.
authors: Onofre
authors: O
authors: Sanmartin
authors: Department of Environmental Epidemiology, National Institute of Environmental Health, Budapest H-1450, Hungary.
authors: Peter
authors: P
authors: Rudnai
authors: Health Department, Environmental Health Centre, Babes Bolyai University, Cluj, RO-Cluj-Napoca, Romania.
authors: Eugene
authors: E
authors: Gurzau
authors: Department of Environmental Health, Regional Authority of Public Health, Banska Bystrica SK-975 56, Slovakia.
authors: Kvetoslava
authors: K
authors: Koppova
authors: Department of Biomedicine, University of Aarhus, Aarhus C DK-8000, Denmark.
authors: Bjørn A
authors: BA
authors: Nexø
authors: Danish Cancer Society Research Centre, DK-2100 Copenhagen Ø, Denmark.
authors: Anne
authors: A
authors: Tjønneland
authors: Department of Public Health, Institute of Epidemiology and Social Medicine, University of Aarhus, Aarhus C DK-8000, Denmark.
authors: Kim
authors: K
authors: Overvad
authors: 1] Landspitali-University Hospital, Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland [3] Icelandic Cancer Registry, Skogarhlid 8, Reykjavik 105, Iceland.
authors: Jon G
authors: JG
authors: Jonasson
authors: 1] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland [2] Icelandic Cancer Registry, Skogarhlid 8, Reykjavik 105, Iceland.
authors: Laufey
authors: L
authors: Tryggvadottir
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Hrefna
authors: H
authors: Johannsdottir
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Anna M
authors: AM
authors: Kristinsdottir
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Hreinn
authors: H
authors: Stefansson
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Gisli
authors: G
authors: Masson
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Olafur T
authors: OT
authors: Magnusson
authors: 1] deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland [2] Institute of Biomedical and Neural Engineering, School of Science and Engineering, Reykjavik University, Reykjavik 101, Iceland.
authors: Bjarni V
authors: BV
authors: Halldorsson
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Augustine
authors: A
authors: Kong
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Thorunn
authors: T
authors: Rafnar
authors: 1] deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
authors: Unnur
authors: U
authors: Thorsteinsdottir
authors: National Research Centre for the Working Environment, Copenhagen DK-2100, Denmark.
authors: Ulla
authors: U
authors: Vogel
authors: Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg D-69120, Germany.
authors: Rajiv
authors: R
authors: Kumar
authors: 1] Department of Oncology, Instituto Valenciano de Oncologia, Valencia 46009, Spain [2] Universidad Católica de Valencia, Valencia 46003, Spain.
authors: Eduardo
authors: E
authors: Nagore
authors: Division of Medical Oncology, University of Colorado, Aurora, Colorado 80045, USA.
authors: José I
authors: JI
authors: Mayordomo
authors: deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland.
authors: Daniel F
authors: DF
authors: Gudbjartsson
authors: 1] Landspitali-University Hospital, Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
authors: Jon H
authors: JH
authors: Olafsson
authors: 1] deCODE Genetics/AMGEN, Sturlugata 8, Reykjavik 101, Iceland [2] Faculty of Medicine, University of Iceland, Reykjavik 101, Iceland.
authors: Kari
authors: K
authors: Stefansson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000235:genetics*; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D002648:Child; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007055:Iceland; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C000606288:FLACC1 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D018398:Homeodomain Proteins; C459801:MYCN protein, human; D008565:Membrane Proteins; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011506:Proteins; D014157:Transcription Factors; C000591861:ZFHX4 protein, human; C505530:CASP8 protein, human; D053181:Caspase 8