Polymorphisms in one-carbon metabolism and trans-sulfuration pathway genes and susceptibility to bladder cancer
Polymorphisms in one-carbon metabolism and trans-sulfuration pathway genes and susceptibility to bladder cancer
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DOI：
10.1002/ijc.22565
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发表时间：
2007-06-01
影响因子：
6.4
通讯作者：
Garcia-Closas, Montserrat
中科院分区：
文献类型：
--
作者：
Moore, Lee E.;Malats, Nuria;Garcia-Closas, Montserrat
我们之前在西班牙进行的一项以医院为基础的膀胱癌病例对照研究中报道了膀胱癌风险与维生素B2、B6、B12、叶酸和蛋白质的饮食摄入量之间的显著负相关（1150例；1149例对照）。由于这些饮食因素参与了单碳代谢途径，我们评估了膀胱癌风险与8个基因（CBS、CTH、MTHFR、MTR、MTRR、SHMT1、SLC19A1和TYMS）的33个单核苷酸多态性（snp）之间的关系，以及与该途径相关的饮食变量之间的相互作用。CTH基因的两个snp与膀胱癌风险显著相关。与纯合子野生型个体相比，杂合子和纯合子变异的OR （95% CI）分别为1.37 (1.04-1.80)IVS3-66 A > C和1.22 (1.02-1.45)IVS10-430 C > t。由于CTH基因对谷胱甘肽合成很重要，我们研究了与编码谷胱甘肽s -转移酶mu u的GSTM1基因的相互作用。没有其他snp与膀胱癌风险相关。这些发现表明，单碳途径中的常见遗传变异可能在膀胱癌的病因学中不起重要作用。然而，我们的研究结果提供了一些证据，表明谷胱甘肽合成的变化可能导致风险，特别是在GSTM1基因缺失的个体中。需要进一步的工作来全面评估CTH和反硫途径相关基因的基因组变异与膀胱癌的风险。(c) 2007 Wiley-Liss, Inc。
We have previously reported significant inverse associations between bladder cancer risk and dietary intake of vitamins B2, B6, B12, folate and protein in a hospital-based bladder cancer case-control study conducted in Spain (1,150 cases;1,149 controls). Because these dietary factors are involved in the one-carbon metabolism pathway, we evaluated associations between bladder cancer risk and 33 single nucleotide polymorphisms (SNPs) in 8 genes (CBS, CTH, MTHFR, MTR, MTRR, SHMT1, SLC19A1 and TYMS) and interactions with dietary variables involved in this pathway. Two SNPs in the CTH gene were significantly associated with bladder cancer risk. OR (95% CI) for heterozygous and the homozygous variants compared to homozygous wild-type individuals were: 1.37 (1.04-1.80) IVS3-66 A > C and 1.22 (1.02-1.45) IVS10-430 C > T. Because the CTH gene is important for glutathione synthesis, we examined interactions with the GSTM1 gene, which codes for glutathione S-transferase mu u. Increased risk for individuals with the IVS10-430 CT or TT genotype was limited to those with the GSTM1 null genotype (p-interaction = 0.02). No other SNPs were associated with risk of bladder cancer. These findings suggest that common genetic variants in the one-carbon pathway may not play an important role in the etiology of bladder cancer. However, our results provide some evidence that variation in glutathione synthesis may contribute to risk, particularly among individuals who carry a deletion in GSTM1. Additional work is needed to comprehensively evaluate genomic variation in CTH and related genes in the trans-sulfuration pathway and bladder cancer risk. (c) 2007 Wiley-Liss, Inc.