Polymorphisms in GSTT1, GSTZ1, and CYP2E1, disinfection by-products, and risk of bladder cancer in Spain.
Polymorphisms in GSTT1, GSTZ1, and CYP2E1, disinfection by-products, and risk of bladder cancer in Spain.
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DOI：
10.1289/ehp.1002206
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发表时间：
2010-11
影响因子：
10.4
通讯作者：
Kogevinas M
中科院分区：
文献类型：
--
作者：
Cantor KP;Villanueva CM;Silverman DT;Figueroa JD;Real FX;Garcia-Closas M;Malats N;Chanock S;Yeager M;Tardon A;Garcia-Closas R;Serra C;Carrato A;Castaño-Vinyals G;Samanic C;Rothman N;Kogevinas M
膀胱癌与长期接触饮用水中的消毒副产物（DBP）有关。在这项研究中，我们在西班牙进行的一项基于医院的病例对照研究中，研究了 DBP 暴露以及谷胱甘肽 S-转移酶 (GSTT1、GSTZ1) 和细胞色素 P450 (CYP2E1) 基因多态性对膀胱癌选定副产物代谢途径的综合影响。根据 680 名病例和 714 名对照者的居住史和城市水源信息，估算了每个受试者从 15 岁起对三卤甲烷（THM；DBP 的替代品）的平均暴露量。我们使用带或不带交互项的调整逻辑回归模型估计了 THM 和 GSTT1、GSTZ1 和 CYP2E1 多态性对膀胱癌的影响。 THM 暴露与膀胱癌呈正相关：相对于第 1 四分位数，THM 第 2、3 和 4 分位数的调整比值比 (OR) 和 95% 置信区间 (CI) 分别为 1.2 (0.8–1.8)、1.8 (1.1–2.9) 和 1.8 (0.9–3.5)。 GSTT1 +/+ 或 +/- 与 GSTT1 null (pinteraction = 0.021)、GSTZ1 rs1046428 CT/TT 与 CC (pinteraction = 0.018) 或 CYP2E1 rs2031920 CC 与 CT/TT (pinteraction = 0.035) 相比。在 GSTT1 和 GSTZ1 高风险形式的 195 例病例和 192 例对照中，THM 第 2、3 和 4 四分位数的 OR 分别为 1.5 (0.7–3.5)、3.4 (1.4–8.2) 和 5.9 (1.8–19.0)。关键代谢酶的多态性改变了 DBP 相关的膀胱癌风险。这些发现与 GSTT1、GSTZ1 和 CYP2E1 活性的实验观察结果的一致性强化了 DBP 导致膀胱癌的假设，并提出了可能的机制以及可能涉及的化合物类别。
Bladder cancer has been linked with long-term exposure to disinfection by-products (DBPs) in drinking water. In this study we investigated the combined influence of DBP exposure and polymorphisms in glutathione S-transferase (GSTT1, GSTZ1) and cytochrome P450 (CYP2E1) genes in the metabolic pathways of selected by-products on bladder cancer in a hospital-based case–control study in Spain. Average exposures to trihalomethanes (THMs; a surrogate for DBPs) from 15 years of age were estimated for each subject based on residential history and information on municipal water sources among 680 cases and 714 controls. We estimated effects of THMs and GSTT1, GSTZ1, and CYP2E1 polymorphisms on bladder cancer using adjusted logistic regression models with and without interaction terms. THM exposure was positively associated with bladder cancer: adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.2 (0.8–1.8), 1.8 (1.1–2.9), and 1.8 (0.9–3.5) for THM quartiles 2, 3, and 4, respectively, relative to quartile 1. Associations between THMs and bladder cancer were stronger among subjects who were GSTT1 +/+ or +/− versus GSTT1 null (pinteraction = 0.021), GSTZ1 rs1046428 CT/TT versus CC (pinteraction = 0.018), or CYP2E1 rs2031920 CC versus CT/TT (pinteraction = 0.035). Among the 195 cases and 192 controls with high-risk forms of GSTT1 and GSTZ1, the ORs for quartiles 2, 3, and 4 of THMs were 1.5 (0.7–3.5), 3.4 (1.4–8.2), and 5.9 (1.8–19.0), respectively. Polymorphisms in key metabolizing enzymes modified DBP-associated bladder cancer risk. The consistency of these findings with experimental observations of GSTT1, GSTZ1, and CYP2E1 activity strengthens the hypothesis that DBPs cause bladder cancer and suggests possible mechanisms as well as the classes of compounds likely to be implicated.
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影响因子：
3.8
作者：
Leavens, Teresa L.;Blount, Benjamin C.;Pegram, Rex A.
通讯作者：
Pegram, Rex A.
影响因子：
3.8
作者：
Pegram, RA;Andersen, ME;Claxton, LD
通讯作者：
Claxton, LD
DOI：
10.1080/009841099157115
发表时间：
1999-12-24
影响因子：
2.6
作者：
DeAngelo, AB;George, MH;House, DE
通讯作者：
House, DE
饮用水中的氯化消毒副产物和先天性异常：回顾和荟萃分析。
影响因子：
10.4
作者：
Nieuwenhuijsen, Mark J.;Martinez, David;Grellier, James;Bennett, James;Best, Nicky;Iszatt, Nina;Vrijheid, Martine;Toledano, Mireille B.
通讯作者：
Toledano, Mireille B.
影响因子：
4.5
作者：
Komulainen, H
通讯作者：
Komulainen, H