Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma
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Katherine J. Ransohoff1,*, Wenting Wu2,*, Hyunje G. Cho1, Harvind C. Chahal1, Yuan Lin2, Hong-Ji Dai2,3, Christopher I. Amos4, Jeffrey E. Lee5, Jean Y. Tang1, David A. Hinds6, Jiali Han2,7,#, Qingyi Wei8,#, Kavita Y. Sarin1,#
1Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA
2Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA
3Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital and Institute, National Clinical Research Center for Cancer, Tianjin and Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
4Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA
5Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
623andMe Inc., Mountain View, CA, USA
7Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
8Duke Cancer Institute, Department of Medicine, Duke University, Durham, NC, USA
Kavita Y. Sarin, email: firstname.lastname@example.org
Keywords: melanoma, genome-wide association study, single nucleotide polymorphism, susceptibility loci, BASP1
Received: December 02, 2016 Accepted: January 27, 2017 Published: February 09, 2017
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 x 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.
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