Περίληψη:
Background Although genetic studies have reported a number of loci
associated with cutaneous melanoma (CM) risk, a comprehensive synopsis
of genetic association studies published in the field and systematic
meta-analysis for all eligible polymorphisms have not been reported.
Methods We systematically annotated data from all genetic association
studies published in the CM field (n = 145), including data from
genome-wide association studies (GWAS), and performed random-effects
meta-analyses across all eligible polymorphisms on the basis of four or
more independent case-control datasets in the main analyses.
Supplementary analyses of three available datasets derived from GWAS and
GWAS-replication studies were also done. Nominally statistically
significant associations between polymorphisms and CM were graded for
the strength of epidemiological evidence on the basis of the Human
Genome Epidemiology Network Venice criteria. All statistical tests were
two-sided.
Results Forty-two polymorphisms across 18 independent loci evaluated in
four or more datasets including candidate gene studies and available
GWAS data were subjected to meta-analysis. Eight loci were identified in
the main meta-analyses as being associated with a risk of CM (P < .05)
of which four loci showed a genome-wide statistically significant
association (P < 1 x 10(-7)), including 16q24.3 (MC1R), 20q11.22
(MYH7B/PIGU/ASIP), 11q14.3 (TYR), and 5p13.2 (SLC45A2). Grading of the
cumulative evidence by the Venice criteria suggested strong
epidemiological credibility for all four loci with genome-wide
statistical significance and one additional gene at 9p23 (TYRP1). In the
supplementary meta-analyses, a locus at 9p21.3 (CDKN2A/MTAP) reached
genome-wide statistical significance with CM and had strong
epidemiological credibility.
Conclusions To the best of our knowledge, this is the first
comprehensive field synopsis and systematic meta-analysis to identify
genes associated with an increased susceptibility to CM.
Συγγραφείς:
Chatzinasiou, Foteini
Lill, Christina M.
Kypreou, Katerina and
Stefanaki, Irene
Nicolaou, Vasiliki
Spyrou, George and
Evangelou, Evangelos
Roehr, Johannes T.
Kodela, Elizabeth and
Katsambas, Andreas
Tsao, Hensin
Ioannidis, John P. A. and
Bertram, Lars
Stratigos, Alexander J.
