Results from a systemic review of 145 genetic
association studies, including data from genome-wide association studies,
published on cutaneous melanoma, researchers determined that five gene variants
are statistically significantly associated with melanoma at the genome-wide
level.
Starting with 745 variants, researchers at the
University of Athens in Greece conducted a meta-analysis on 42 polymorphisms
across 18 independent loci. Nineteen polymorphisms in eight loci had
“nominally statistically significant associations” with cutaneous
melanoma.
Researchers then calculated a median summary OR (1.25)
based on the best result per gene, defined according to the single nucleotide
polymorphism with the best Venice score and then according to P score,
to account for the effect of loci with multiple-associated SNPs. They concluded
that there were four loci with genome-wide statistical significance:
MC1R (rs1805007, rs1805008 and rs1805009), MYH7B/PIGU (rs1885120
and rs910873), TYR (rs1126809 and rs1393350) and SLC45A2
(rs16891982).
Using Venice interim criteria, researchers determined
the variant with the best graded result per genetic locus. Five loci
(SLC45A2, TYRP1, TYR, MC1R and MIYH7B) had
strong epidemiological credibility for at least one SNP. Three others —
CDKN2A, VDR and CLPTM1L — had only weak credibility.
In a supplementary meta-analysis of data from
genome-wide association studies (GWAS) and GWAS-replication studies, four
variants (rs10757257, rs2218220, rs1335510, and rs7023329) in the
CDKN2A/MTAP locus showed a statistically significant genome-wide
association with melanoma and had an overall strong epidemiological
credibility.
“Thus, assuming one single underlying association
signal in this region, the CDKN2A/MTAP locus has strong cumulative
evidence for association with cutaneous melanoma as well,” researchers
wrote.