TY - JOUR
T1 - Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma
AU - Ransohoff, Katherine J.
AU - Wu, Wenting
AU - Cho, Hyunje G.
AU - Chahal, Harvind C.
AU - Lin, Yuan
AU - Dai, Hong Ji
AU - Amos, Christopher I.
AU - Lee, Jeffrey E.
AU - Tang, Jean Y.
AU - Hinds, David A.
AU - Han, Jiali
AU - Wei, Qingyi
AU - Sarin, Kavita Y.
N1 - Funding Information:
We would like to thank the research participants and employees of 23andMe for making this work possible. The authors assume full responsibility for analyses and interpretation of these data. This work was supported by the National Human Genome Research Institute of the National Institutes of Health (grant number R44HG006981), and in part by NIH R01 CA49449, P01 CA87969, UM1 CA186107, UM1 CA167552, the Stanford TRAM (Translational Research and Applied Medicine) Program and the Dermatology Foundation Career Development Award (KS).
PY - 2017
Y1 - 2017
N2 - 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 metaanalysis 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 genomewide 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.
AB - 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 metaanalysis 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 genomewide 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.
KW - BASP1
KW - Genome-wide association study
KW - Melanoma
KW - Single nucleotide polymorphism
KW - Susceptibility loci
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U2 - 10.18632/oncotarget.15230
DO - 10.18632/oncotarget.15230
M3 - Article
C2 - 28212542
AN - SCOPUS:85015195287
SN - 1949-2553
VL - 8
SP - 17586
EP - 17592
JO - Oncotarget
JF - Oncotarget
IS - 11
ER -