New basal cell carcinoma susceptibility loci

Nat Commun. 2015 Apr 9;6:6825. doi: 10.1038/ncomms7825.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Basal Cell / genetics*
  • Case-Control Studies
  • Caspase 8 / genetics*
  • Child
  • European Continental Ancestry Group / genetics
  • Female
  • GATA3 Transcription Factor / genetics*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Homeodomain Proteins / genetics*
  • Humans
  • Iceland
  • Male
  • Membrane Proteins
  • Middle Aged
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins / genetics*
  • Oncogene Proteins / genetics*
  • Proteins / genetics*
  • Skin Neoplasms / genetics*
  • Transcription Factors / genetics*
  • Young Adult

Substances

  • FLACC1 protein, human
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Homeodomain Proteins
  • MYCN protein, human
  • Membrane Proteins
  • N-Myc Proto-Oncogene Protein
  • Nuclear Proteins
  • Oncogene Proteins
  • Proteins
  • Transcription Factors
  • ZFHX4 protein, human
  • CASP8 protein, human
  • Caspase 8