Chapter 124

Cutaneous Melanoma
Evans C. Bailey, Arthur J. Sober,
Hensin Tsao, Martin C. Mihm Jr,
& Timothy M. Johnson

ETIOLOGY AND PATHOGENESIS

Risk Factors
LOW TO MODERATE RISK SINGLE
NUCLEOTIDE POLYMORPHISMS (SNPs).
Several genome-wide association studies (GWAS)
have identified SNPs that tag risk conferring
chromosomal regions. In one study from Iceland,
investigators found evidence for risk SNPs around
various pigmentation-associated loci: SLC24A4
(solute carrier family 24), KITLG (KIT ligand), 6p25.3,
TYR (tyrosinase), OCA2 (oculocutaneous albinism II),
TPCN2 (two-pore segment channel 2), ASIP (Agouti
signal protein), and TYRP1 (tyrosinase-related
protein 1).52 Studies from GenoMELthe International Melanoma Genetics Consortiumhave also
independently identified risk-conferring SNPs on
20q11,53 11q14 (TYR) and 9p21 (CDKN2A-MTAP).54
The emerging picture from these GWAS analyses is
that sporadic melanoma risk is still heavily modulated by pigmentary status and probably sun exposure. Regardless, the level of risk associated with
these SNPs is often under twofold and the biological mechanisms underlying this predisposition are
still unknown.

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