Association between putative functional variants in the PSMB9 gene and risk of melanoma – re‐analysis of published melanoma genome‐wide association studies. (27th March 2013)

• Record Type: Journal Article
• Authors: Qian, Ji; Liu, Hongliang; Wei, Sheng; Liu, Zhensheng; Li, Yangkai; Wang, Li‐E; Chen, Wei V.; Amos, Christopher I.; Lee, Jeffrey E.; Iles, Mark M.; Law, Matthew H.; Cust, Anne E.; Barrett, Jennifer H.; Montgomery, Grant W.; Taylor, John; Bishop, Julia A. Newton; MacGregor, Stuart; Bishop, D. Timothy; Mann, Graham J.; Hayward, Nicholas K.; Wei, Qingyi
• Is Part Of: Pigment cell & melanoma research. Volume 26:Number 3(2013:May)
• Page Start: 392
• Page End: 401
• Publication Date: 2013-03-27
• Subjects: Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.12069
• Languages: English
• ISSNs: 1755-1471

Abstract

<abstract abstract-type="main" id="pcmr12069-abs-0001"> <title>Summary</title> <p>To mine possibly hidden causal single‐nucleotide polymorphisms (SNPs) of melanoma, we investigated the association of SNPs in 76 M/G1 transition genes with melanoma risk using our published genome‐wide association study (GWAS) data set with 1804 melanoma cases and 1026 cancer‐free controls. We found multiple SNPs with P<italic> </italic>&lt; 0.01 and performed validation studies for 18 putative functional SNPs in <italic>PSMB9</italic> in two other GWAS data sets. Two SNPs (rs1351383 and rs2127675) were associated with melanoma risk in the GenoMEL data set (P<italic> </italic>=<italic> </italic>0.013 and 0.004, respectively), but failed in validation using the Australian data set. Genotype–phenotype analysis revealed these two SNPs were significantly correlated with mRNA expression level of <italic>PSMB9</italic>. Further experiments revealed that SNP rs2071480, which is in high LD with rs1351383 and rs2127675, may have a weak effect on the promoter activity of <italic>PSMB9</italic>. Taken together, our data suggested that functional variants in <italic>PSMB9</italic> may contribute to melanoma susceptibility.</p> </abstract>