Genetics of pigmentation and melanoma predisposition

L. N. Pho, Sancy Leachman

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

About 5-10% of human cutaneous malignant melanoma is hereditary and known to involve rare germline mutations in highly penetrant, autosomal dominant genes. These genes are important in cell cycle control but are not responsible for all familial cases of melanoma. Epidemiologic studies have linked specific phenotypic traits including fair skin, light-colored eyes, and poor tanning ability to melanoma risks. The ability to visually discern and define pigmentary phenotypes in humans and in animal models has permitted elucidation of many genes involved in pigmentation and melanin biosynthesis. Additional genetic epidemiological studies have recently identified a subset of these pigmentation genes that are associated with risk for melanoma and other cutaneous malignancies as well as photosensitivity. Genome-wide association studies (GWAS) have unveiled single nucleotide polymorphisms (SNPs) or genetic variants in MC1R, TPCN2, ASIP, KITLG, NCKX5, TYR, IRF4, OCA2, and TYRP1 pigmentation genes. These findings emphasize the contribution of pigmentation pathways to melanoma predisposition and tumorigenesis through gene-environment interactions. Since pigmentation genes in the melanin synthesis pathway also confer risk for cutaneous malignancy, a better understanding of the operative molecular mechanisms involved in this relationship has the potential to impact individual risk assessment for cutaneous malignant melanoma in the future. This paper is an overview of our current understanding of pigmentation gene modifications that have been associated with melanoma risk and how these genes can enrich clinical management, prevention, and early detection of malignant melanoma.

Original languageEnglish (US)
Pages (from-to)37-45
Number of pages9
JournalGiornale Italiano di Dermatologia e Venereologia
Volume145
Issue number1
StatePublished - 2010
Externally publishedYes

Fingerprint

Pigmentation
Melanoma
Genes
Melanins
Skin
Epidemiologic Studies
Tanning
Dominant Genes
Gene-Environment Interaction
Germ-Line Mutation
Genome-Wide Association Study
Cell Cycle Checkpoints
Single Nucleotide Polymorphism
Neoplasms
Carcinogenesis
Animal Models
Phenotype
Cutaneous Malignant Melanoma

Keywords

  • Germ-line mutations
  • Polymorphism
  • Single nucleotide
  • Skin neoplasms
  • Ultraviolet rays

ASJC Scopus subject areas

  • Dermatology

Cite this

Genetics of pigmentation and melanoma predisposition. / Pho, L. N.; Leachman, Sancy.

In: Giornale Italiano di Dermatologia e Venereologia, Vol. 145, No. 1, 2010, p. 37-45.

Research output: Contribution to journalArticle

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