ABSTRACT: This study sought to determine the role of copy number variants (CNV) combined with other genetic variants in the Glutathione S-transferases Mu class1 (GSTM1) promoter in the development of urinary bladder cancer. TaqMan real-time PCR and direct sequencing were used to determine genetic variants. Haploblocks and haplotype were constructed and estimated by Haploview and Phase, respectively. Logistic regression revealed a significantly decreased bladder cancer risk in subjects with at least 2 copies of GSTM1 (OR=0.56; 95%CI=0.39-0.81) but not in those with 1 copy of the gene. GSTM1 promoter screening revealed an insertion variant (-1543TTCT) and 14 single nucleotide polymorphisms (SNPs) (-1529C>G, -1490A>G, -1143A>G, -888A>T, -498G>C, -486C>G, -471C>T, -426G>A, -344C>T, -343A>T, -341C>T, -339C>T, -304G>A, and -164C>T). Four haploblocks were evident by Haploview. There was no significant association between any single SNP/haplotype and bladder cancer risk. However, when stratified by copy number, the two copy carriers with the -1543 insertion had decreased bladder cancer risk (OR, 0.58; 95%CI, 0.32-0.10) and similar results were found in two copy carriers with -888 A, -486G, - 344 C, -343 A, -341 C allele and haplotype INS(-1543)-C(-1529)-A(-1429) in LD block 1, A(-1143)-A(-888) in LD block 2, C(-498)-G(-486)-T(-471) in LD block 3, C(-344)-A(-343)-C(-341)-C(-339) and C(-344)-A(-343)-C(-341)-T(-339) in LD block 4. These results suggest that GSTM1 CNV is a better predictor of bladder cancer susceptibility than measuring presence/absence of GSTM1 and other genetic variants also can modify bladder cancer risk.