Abstract
Genome-wide association studies have identified 21 susceptibility loci associated with melanoma. These loci implicate genes affecting pigmentation, nevus count, telomere maintenance, and DNA repair in melanoma risk. Here, we report the results of a two-stage genome-wide association study of melanoma. The stage 1 discovery phase consisted of 4,842 self-reported melanoma cases and 286,565 controls of European ancestry from the 23andMe research cohort and the stage 2 replication phase consisted of 1,804 melanoma cases and 1,026 controls from the University of Texas M.D. Anderson Cancer Center. We performed a combined meta-analysis totaling 6,628 melanoma cases and 287,591 controls. Our study replicates 20 of 21 previously known melanoma-loci and confirms the association of the telomerase reverse transcriptase, TERT, with melanoma susceptibility at genome-wide significance. In addition, we uncover a novel polymorphism, rs187843643 (OR = 1.96; 95% CI = [1.54, 2.48]; P = 3.53 × 10−8), associated with melanoma. The SNP rs187842643 lies within a noncoding RNA 177kb downstream of BASP1 (brain associated protein-1). We find that BASP1 expression is suppressed in melanoma as compared with benign nevi, providing additional evidence for a putative role in melanoma pathogenesis.
Highlights
Melanoma represents 1% of cutaneous malignancies, affecting approximately 76,000 people per year in the U.S, but causes the majority of skin cancer deaths [1]
We find that brain abundant membrane attached signal protein 1 (BASP1) expression is suppressed in melanoma as compared with benign nevi, providing additional evidence for a putative role in melanoma pathogenesis
Stage 1 consisted of 4,842 self-reported melanoma cases and 286,565 controls of European ancestry from the 23andMe, Inc. research cohort (Table 1)
Summary
Melanoma represents 1% of cutaneous malignancies, affecting approximately 76,000 people per year in the U.S, but causes the majority of skin cancer deaths [1]. Environmental risk factors such as ultraviolet radiation and fair skin pigmentation contribute to melanoma development [2]. We utilize crowd-sourced data in a two-stage genome-wide association meta-analysis for melanoma, totaling 6,628 cases and 287,591 controls. In this GWAS, we replicate 20 of 21 previously identified melanoma-associated loci and discover one novel susceptibility locus at genome-wide significance
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