Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma

Katherine J. Ransohoff, Wenting Wu, Hyunje G. Cho, Harvind C. Chahal, Yuan Lin, Hong Ji Dai, Christopher I. Amos, Jeffrey E. Lee, Jean Y. Tang, David A. Hinds, Jiali Han, Qingyi Wei, Kavita Y. Sarin

Research output: Contribution to journalArticle

21 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)17586-17592
Number of pages7
JournalOncotarget
Volume8
Issue number11
DOIs
StatePublished - Jan 1 2017

Keywords

  • BASP1
  • Genome-wide association study
  • Melanoma
  • Single nucleotide polymorphism
  • Susceptibility loci

ASJC Scopus subject areas

  • Oncology

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    Ransohoff, K. J., Wu, W., Cho, H. G., Chahal, H. C., Lin, Y., Dai, H. J., Amos, C. I., Lee, J. E., Tang, J. Y., Hinds, D. A., Han, J., Wei, Q., & Sarin, K. Y. (2017). Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma. Oncotarget, 8(11), 17586-17592. https://doi.org/10.18632/oncotarget.15230