ASIP and TYR Pigmentation Variants Associate With Cutaneous Melanoma and Basal Cell Carcinoma

Nat Genet. 2008 Jul;40(7):886-91. doi: 10.1038/ng.161. Epub 2008 May 18.

Abstract

Fair color increases risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC). Recent genome-wide association studies have identified variants affecting hair, eye and skin pigmentation in Europeans. Here, we assess the effect of these variants on risk of CM and BCC in European populations comprising 2,121 individuals with CM, 2,163 individuals with BCC and over 40,000 controls. A haplotype near ASIP, known to affect a similar spectrum of pigmentation traits as MC1R variants, conferred significant risk of CM (odds ratio (OR) = 1.45, P = 1.2 x 10(-9)) and BCC (OR = 1.33, P = 1.2 x 10(-6)). The variant in TYR encoding the R402Q amino acid substitution, previously shown to affect eye color and tanning response, conferred risk of CM (OR = 1.21, P = 2.8 x 10(-7)) and BCC (OR = 1.14, P = 6.1 x 10(-4)). An eye color variant in TYRP1 was associated with risk of CM (OR = 1.15, P = 4.6 x 10(-4)). The association of all three variants is robust with respect to adjustment for the effect of pigmentation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Agouti Signaling Protein / genetics*
  • Carcinoma, Basal Cell / genetics*
  • Carcinoma, Basal Cell / pathology
  • Case-Control Studies
  • Europe
  • Eye Color / genetics
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Melanoma / genetics*
  • Melanoma / pathology
  • Membrane Glycoproteins / genetics
  • Middle Aged
  • Monophenol Monooxygenase / genetics*
  • Neoplasm Metastasis
  • Odds Ratio
  • Oxidoreductases / genetics
  • Pigmentation / genetics*
  • Polymorphism, Single Nucleotide
  • Receptor, Melanocortin, Type 1 / genetics
  • Registries
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology

Substances

  • ASIP protein, human
  • Agouti Signaling Protein
  • Membrane Glycoproteins
  • Receptor, Melanocortin, Type 1
  • Oxidoreductases
  • TYRP1 protein, human
  • Monophenol Monooxygenase