Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk
Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk
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DOI：
10.1093/carcin/bgl095
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发表时间：
2006-12-01
期刊：
影响因子：
4.7
通讯作者：
Yokota, Jun
中科院分区：
文献类型：
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作者：
Kohno, Takashi;Sakiyama, Tokuki;Yokota, Jun
通过一项包括211例小细胞肺癌（SCLC）病例和685例对照的病例对照研究，评估了与36个参与不同DNA修复途径的基因的氨基酸变化相关的50个单核苷酸多态性（SNP）与小细胞肺癌（SCLC）风险的相关性。MTH 1中的SNP Val 83 Met（mutT同源物1）编码水解促诱变氧化核苷三磷酸（如8-羟基-dGTP和2-羟基-dATP）的三磷酸酶的基因显示出与SCLC风险的最强和显著关联[比值比（OR）= 1.6，95%置信区间（CI）：1.2-2.2，P = 0.004]，而TP 53、BLM和SNM 1基因的其他三个SNP也显示出边缘关联（0.05 < P < 0.1）。另一个SNP，其引起MTH 1转录物的5 '-UTR中的核苷酸变化，导致替代翻译起始，被另外检查，并且SNP也显示出显著关联（OR = 1.7，95%CI：1.2-2.3，P = 0.002）。MTH 1基因中的两个SNP处于连锁不平衡状态，携带由两个危险SNP等位基因组成的单倍型的OR为2.0（95%CI：1.2-3.2，P = 0.002）。目前的研究结果表明，MTH 1活性的个体间差异，由于SNPs参与小细胞肺癌的易感性。
Fifty single-nucleotide polymorphisms (SNPs) associated with amino acid changes in 36 genes involved in diverse DNA repair pathways were assessed for associations with risk for small cell lung carcinoma (SCLC) by a case-control study consisting of 211 SCLC cases and 685 controls. An SNP, Val83Met, in the MTH1 (mutT homolog 1) gene encoding a triphosphatase that hydrolyzes pro-mutagenic oxidized nucleoside triphosphates, such as 8-hydroxy-dGTP and 2-hydroxy-dATP, showed the strongest and a significant association with SCLC risk [odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.2-2.2, P = 0.004], while three other SNPs in the TP53, BLM and SNM1 genes, respectively, also showed marginal associations (0.05 < P < 0.1). Another SNP, which causes a nucleotide change in the 5'-UTR of MTH1 transcripts leading to alternative translation initiation, was additionally examined and the SNP also showed a significant association (OR = 1.7, 95% CI: 1.2-2.3, P = 0.002). The two SNPs in the MTH1 gene were in linkage disequilibrium, and the OR for carrying a copy of the haplotype consisting of both the risky SNP alleles was 2.0 (95% CI: 1.2-3.2, P = 0.002). The present results indicate that inter-individual differences in MTH1 activities due to SNPs are involved in susceptibility to SCLC.