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.