GSTM-1 and NAT2 and genetic alterations in colon tumors
GSTM-1 and NAT2 and genetic alterations in colon tumors
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DOI：
10.1023/a:1016376016716
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发表时间：
2002-08-01
影响因子：
2.3
通讯作者：
Samowitz, W
中科院分区：
文献类型：
--
作者：
Slattery, ML;Curtin, K;Samowitz, W
目的：谷胱甘肽S-转移酶和N-乙酰转移酶等Ⅱ相代谢酶参与致癌物的解毒过程。已经评估了编码这些酶的基因的遗传变体与结肠癌的关联，既作为独立的风险因素，又作为与饮食和吸烟关联的效应调节剂。在这项研究中，我们评估GSTM-1基因型和NAT 2-插补表型和获得性突变在tumorsMethods之间的关联：数据取自一组1836例和1958例结肠癌对照，他们是结肠癌的大型病例对照研究的一部分，其肿瘤先前进行了Ki-ras，p53和微卫星不稳定性（MSI）分析。我们还评估了这些遗传变异与饮食和吸烟的修饰作用，这些因素以前被确定为与特定的肿瘤alternations.Results相关：既不是GSTM-1也不是NAT 2-插补表型与Ki-ras，p53，或MSI独立相关。吸烟显著增加了涉及MSI通路的肿瘤的风险。此外，吸烟使存在GSTM-1的人中p53颠换突变的风险增加一倍。如果患者经常食用红肉，并且相对于缓慢表型/不经常食用红肉，具有插补的NAT 2中间/快速表型，则患者发生p53突变的可能性略高（OR 2.0，95% CI 1.3-3.0，中间/快速）。这些数据支持饮食和吸烟可能与特定的疾病途径有关，尽管GSTM-1和NAT 2似乎不能独立地改变对这些饮食和生活方式因素的易感性。
Objective: Phase II metabolizing enzymes such as glutathione S-transferases and N-acetyltransferase are involved in the detoxification of carcinogens. Genetic variants of genes coding for these enzymes have been evaluated as to their association with colon cancer, both as independent risk factors and as effect modifiers for associations with diet and cigarette smoking. In this study, we evaluate associations between the GSTM-1 genotype and the NAT2-imputed phenotype and acquired mutations in tumorsMethods: Data is taken from a set of 1836 cases and 1958 controls with colon cancer who were part of a large case-control study of colon cancer and whose tumors were previously analyzed for Ki-ras, p53, and microsatellite instability (MSI). We also evaluate the modifying effects of these genetic variants with diet and cigarette smoking, factors previously identified as being associated with specific tumor alterations.Results: Neither GSTM-1 nor the NAT2-imputed phenotype was independently associated with Ki-ras, p53, or MSI. Cigarette smoking significantly increased the risk of tumors involving the MSI pathway. Additionally, cigarette smoking doubled the risk of p53 transversion mutations among those who were GSTM-1 present. Cases were slightly more likely to have a p53 mutation if they frequently consumed red meat and had the imputed NAT2 intermediate/rapid phenotype relative to slow phenotype/infrequent consumers of red meat (OR 2.0, 95% CI 1.3-3.0 for intermediate/rapid).Conclusions: These data provide support that diet and cigarette smoking may be associated with specific disease pathways, although GSTM-1 and NAT2 do not independently appear to alter susceptibility to these diet and lifestyle factors.