New common variants affecting susceptibility to basal cell carcinoma

Nat Genet. 2009 Aug;41(8):909-14. doi: 10.1038/ng.412. Epub 2009 Jul 5.

Abstract

In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 x 10(-9)). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 x 10(-9)), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 x 10(-10)). The effect of rs157935[T] is dependent on the parental origin of the risk allele. None of these variants were found to be associated with melanoma or fair-pigmentation traits. A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. Finally, we report conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma.

Publication types

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

MeSH terms

  • Carcinoma, Basal Cell / complications
  • Carcinoma, Basal Cell / genetics*
  • Carcinoma, Squamous Cell / genetics
  • Chromosomes, Human, Pair 7 / genetics
  • Chromosomes, Human, Pair 9 / genetics
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / genetics
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Keratin-5 / genetics
  • Linkage Disequilibrium / genetics
  • Melanoma / pathology
  • Membrane Proteins / genetics
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Skin Neoplasms / complications
  • Skin Neoplasms / genetics*

Substances

  • CLPTM1L protein, human
  • Keratin-5
  • Membrane Proteins
  • Neoplasm Proteins

Associated data

  • GENBANK/DQ485453
  • RefSeq/NM_000424
  • RefSeq/NP_000415
  • RefSeq/NP_001012527