Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma

Abstract

Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international two-stage meta-analysis of 11 genome-wide association studies (GWAS, five unpublished) of CMM and Stage two datasets, totaling 15,990 cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5×10−8) as did two previously-reported but un-replicated loci and all thirteen established loci. Novel SNPs fall within putative melanocyte regulatory elements, and bioinformatic and eQTL data highlight candidate genes including one involved in telomere biology.

Genome-Wide Association Studies in Glioma

“…The risk allele of rs11598018 ( C ) is associated with increased leukocyte telomere length thereby supporting a relationship between genotype and biology (78–80). Variation at 10q24.33 is additionally associated with risk of melanoma (81), basal cell carcinoma (82), thyroid cancer (83), and renal cell carcinoma (84). The SNPs defined by these associations do not appear to be correlated with rs11598018 ( r 2 = 0.11–0.12, D′ = 0.72–1.0).…”

Melanoma genetics

“…PLA2G6 is associated with pigmentation and naevi, while CASP8 , TERT , AGR3 , MTAP/CDKN2A and FTO are associated with variation in naevus density 14 61 63 65–67 69–78. In addition to its role in naevus count, TERT is also associated with telomere length, as is OBFC1 73. Two loci ( PARP1 , ATM ) are associated with DNA repair, and two others are linked to methylthiolation of tRNA and regulation of cell cycle progression ( CDKAL1 and CCND1, respectively) 65 73 79 80.…”

“…In addition to its role in naevus count, TERT is also associated with telomere length, as is OBFC1 73. Two loci ( PARP1 , ATM ) are associated with DNA repair, and two others are linked to methylthiolation of tRNA and regulation of cell cycle progression ( CDKAL1 and CCND1, respectively) 65 73 79 80. Four other loci: ARNT/SETDB1 , CYP1B1 , MX2 and TMEM38B / RAD23B , are associated with melanoma but via uncertain mechanisms 65 73 79…”

What Is New in Melanoma Genetics and Treatment?

“…Genome-wide analyses using a case-control design have reported many more common low-penetrance single-nucleotide polymorphisms associated with increased melanoma risk [4]. Many of these genes can be grouped into pigmentation or naevus genes but many others are not really linked to specific skin phenotypes.…”