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Although recent genome-wide association studies (GWASs) identified several single nucleotide polymorphisms (SNPs) involved in melanoma etiology, these SNPs tend to be related to the known biological pathways.To further mine possibly hidden causal SNPs in our published GWAS dataset for 1804 melanoma cases and 1,026 cancer-free controls (the M.D.Anderson dataset), we identified 68 tagSNPs associated with melanoma risk with a P value <10-2 among c1149 tagSNPs in 76 genes involved in the M/G1 transition of mitotic cell-cycle pathway, of which 18 SNPs in PSMB9 with potential functions were selected for the in silico replication by two additional melanoma GWASs (United Kingdom and Australia) of 4,972 cases and 12,005 controls.In a meta-analysis including M.D.Anderson, United Kingdom, and Australia datasets, we found a weak risk association with rs1351383 in the first intron of PSMB9 (P =0.052) and a stronger association with rs2127675 outside of the PSMB9 region (P =6.03 × 10-3).Individuals with AC/CC genotypes ofrs1351383 and GG/AG genotypes of rs2127675 had higher mRNA expression levels of PSMB9 (PADD =0.0486 and 0.0237, respectively) in 90 CEU cell lines.Functional study by a reporter gene expression assay on the PSMB9 promoter SNP rs2071480 in high LD (r2=0.998) with the replicated SNP rs1351383 suggested that rs2071480 may affect the transcription of PSMB9.These data showed possible roles of functional PSMB9 variants in susceptibility to melanoma.Further studies are warranted to validate our findings and investigate potential molecular mechanisms underlying these associations.