Germline sequence variants in TGM3 and RGS22 confer risk of basal cell carcinoma

Hum Mol Genet. 2014 Jun 1;23(11):3045-53. doi: 10.1093/hmg/ddt671. Epub 2014 Jan 8.

Abstract

To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide association study of 38.5 million single nucleotide polymorphisms (SNPs) and small indels identified through whole-genome sequencing of 2230 Icelanders. We imputed genotypes for 4208 BCC patients and 109 408 controls using Illumina SNP chip typing data, carried out association tests and replicated the findings in independent population samples. We found new BCC susceptibility loci at TGM3 (rs214782[G], P = 5.5 × 10(-17), OR = 1.29) and RGS22 (rs7006527[C], P = 8.7 × 10(-13), OR = 0.77). TGM3 encodes transglutaminase type 3, which plays a key role in production of the cornified envelope during epidermal differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Surface / genetics*
  • Carcinoma, Basal Cell / genetics*
  • Child
  • Female
  • GTP-Binding Protein Regulators / genetics*
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genome-Wide Association Study
  • Genotype
  • Germ Cells / metabolism
  • Germ-Line Mutation*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Skin Neoplasms / genetics
  • Transglutaminases / genetics*
  • Young Adult

Substances

  • Antigens, Surface
  • GTP-Binding Protein Regulators
  • regulator of G-protein signaling 22, human
  • TGM3 protein, human
  • Transglutaminases