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首页> 美国卫生研究院文献>International Journal of Molecular Epidemiology and Genetics >Association between GSTM1 copy number promoter variants and susceptibility to urinary bladder cancer
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Association between GSTM1 copy number promoter variants and susceptibility to urinary bladder cancer

机译：GSTM1拷贝数启动子变体与膀胱癌易感性之间的关联

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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.
机译：这项研究试图确定在谷胱甘肽S-转移酶Mu class1（GSTM1）启动子中拷贝数变异（CNV）与其他遗传变异的结合在膀胱癌发展中的作用。 TaqMan实时PCR和直接测序用于确定遗传变异。单倍型和单倍型分别由Haploview和Phase构建和估计。 Logistic回归显示，患有至少2个GSTM1拷贝的受试者（OR = 0.56； 95％CI = 0.39-0.81）的受试者患膀胱癌的风险显着降低，而具有1个拷贝的基因的受试者则没有。 GSTM1启动子筛选显示插入变异（-1543TTCT）和14个单核苷酸多态性（SNP）（-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和-164C> T）。 Haploview可以明显地看到四个单元格块。在任何单个SNP /单倍型与膀胱癌风险之间没有显着关联。然而，当按拷贝数分层时，插入-1543的两个拷贝携带者的膀胱癌风险降低（OR，0.58； 95％CI，0.32-0.10），在带有-888 A的两个拷贝携带者中发现相似的结果，- LD模块1中的486G，-344 C，-343 A，-341 C等位基因和单倍型INS-1543-C-1529-A-1429在LD模块2中的A-1143-A-888 LD块3中的486-T-471，LD块4中的C-344-A-343-C-341-C-339和C-344-A-343-C-341-T-339与测量GSTM1的存在与否相比，GSTM1 CNV可以更好地预测膀胱癌的易感性，其他遗传变异也可以改变膀胱癌的风险。

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