Updated Field Synopsis and Systematic Meta-Analyses of Genetic Association Studies in Cutaneous Melanoma: The MelGene Database

Abstract

We updated a field synopsis of genetic associations of cutaneous melanoma (CM) by systematically retrieving and combining data from all studies in the field published as of August 31, 2013. Data were available from 197 studies, which included 83,343 CM cases and 187,809 controls and reported on 1,126 polymorphisms in 289 different genes. Random-effects meta-analyses of 81 eligible polymorphisms evaluated in >4 data sets confirmed 20 single-nucleotide polymorphisms across 10 loci (TYR, AFG3L1P, CDK10, MYH7B, SLC45A2, MTAP, ATM, CLPTM1L, FTO, and CASP8) that have previously been published with genome-wide significant evidence for association (P<5 × 10(-8)) with CM risk, with certain variants possibly functioning as proxies of already tagged genes. Four other loci (MITF, CCND1, MX2, and PLA2G6) were also significantly associated with 5 × 10(-8)<P<1 × 10(-3). In supplementary meta-analyses derived from genome-wide association studies, one additional locus located 11 kb upstream of ARNT (chromosome 1q21) showed genome-wide statistical significance with CM. Our approach serves as a useful model in analyzing and integrating the reported germline alterations involved in CM.

Identification of cancer‐related potential biomarkers based on lncRNA–pseudogene–mRNA competitive networks

“…Moreover, we also found that some pseudogenes, such as AFG3L1P, MRPS31P4, RP11‐640M9.2 and HERC2P9, served as biomarkers and could be found in multiple cancers. AFG3L1P was confirmed to be related to melanomas . Notably, in the present study, MRPS31P4 was shown to be related to KIRP and KIRC patient survival, suggesting that it was important for kidney cancer.…”

Prediction of Melanoma Risk in a Southern European Population Based on a Weighted Genetic Risk Score

“…Fifty-five of 59 SNPs were genotyped with call rates !97%. Fifty-three SNPs were considered in the final analysis, of which 26 were genome-wide significantly associated with CM based on the MelGene field synopsis and meta-analysis (Antonopoulou et al, 2015;Chatzinasiou et al, 2011) or on independent GWAS (details in Supplementary Materials online).…”

“…The selection of variants was mainly based on the MelGene field synopsis of genetic associations of melanoma, which systematically curates and meta-analyzes all published melanoma-associated variants (Antonopoulou et al, 2015). Most variants with significant effects in our dataset pertained to genes controlling pigmentary traits.…”

“…This included 10 previously reported GWS SNPs, specifically rs16891982, rs1805007, rs401681, rs1885120, rs4636294, and rs10931936 (Antonopoulou et al, 2015), as well as rs12918773, rs10739221, rs4778138, and rs17119490 (Barrett et al, 2011;Bishop et al, 2009;Law et al, 2015). Among the five new loci identified in the most recent GWAS meta-analysis (Law et al, 2015), the intergenic SNP with rs10739221 near TMEM38B, ZNF462, and RAD23B as well as the SNP with rs4778138 (OCA2) were also significantly associated with CM in our dataset (rs10739221: odds ratio [OR] ¼ 1.21, P ¼ 0.015; rs4778138: OR ¼ 0.83, P ¼ 0.014; Table 1) (Law et al, 2015).…”

“…Most of these SNPs (n ¼ 52) were selected from MelGene (www.melgene.org), a continuously updated database for CM genetic association studies (Antonopoulou et al, 2015;Athanasiadis et al, 2014;Chatzinasiou et al, 2011). We further included seven GWAS SNPs from a recent GWAS metaanalysis, which were tested in our cohort as part of the replication phase (Law et al, 2015).…”