Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH 03756, USA.
Toxicol Lett. 2012 Apr 5;210(1):100-6. doi: 10.1016/j.toxlet.2012.01.015. Epub 2012 Jan 28.
Arsenic is associated with bladder cancer risk even at low exposure levels. Genetic variation in enzymes involved in xenobiotic and arsenic metabolism may modulate individual susceptibility to arsenic-related bladder cancer. Through a population-based case-control study in NH (832 cases and 1191 controls), we investigated gene-environment interactions between arsenic metabolic gene polymorphisms and arsenic exposure in relation to bladder cancer risk. Toenail arsenic concentrations were used to classify subjects into low and high exposure groups. Single nucleotide polymorphisms (SNPs) in GSTP1, GSTO2, GSTZ1, AQP3, AS3MT and the deletion status of GSTM1 and GSTT1 were determined. We found evidence of genotype-arsenic interactions in the high exposure group; GSTP1 Ile105Val homozygous individuals had an odds ratio (OR) of 5.4 [95% confidence interval (CI): 1.5-20.2; P for interaction=0.03] and AQP3 Phe130Phe carriers had an OR=2.2 (95% CI: 0.8-6.1; P for interaction=0.10). Bladder cancer risk overall was associated with GSTO2 Asn142Asp (homozygous; OR=1.4; 95% CI: 1.0-1.9; P for trend=0.06) and GSTZ1 Glu32Lys (homozygous; OR=1.3; 95% CI: 0.9-1.8; P for trend=0.06). Our findings suggest that susceptibility to bladder cancer may relate to variation in genes involved in arsenic metabolism and oxidative stress response and potential gene-environment interactions requiring confirmation in other populations.
砷即使在低暴露水平下也与膀胱癌风险相关。参与外源性和砷代谢的酶的遗传变异可能会调节个体对砷相关膀胱癌的易感性。我们通过在 NH 进行的一项基于人群的病例对照研究（832 例病例和 1191 例对照），研究了砷代谢基因多态性与砷暴露之间的基因-环境相互作用与膀胱癌风险的关系。我们使用趾甲砷浓度将受试者分为低暴露组和高暴露组。确定 GSTP1、GSTO2、GSTZ1、AQP3、AS3MT 的单核苷酸多态性（SNP）以及 GSTM1 和 GSTT1 的缺失状态。我们在高暴露组中发现了基因型-砷相互作用的证据；GSTP1 Ile105Val 纯合子个体的比值比（OR）为 5.4（95%置信区间[CI]：1.5-20.2；P 交互作用=0.03），AQP3 Phe130Phe 携带者的 OR=2.2（95% CI：0.8-6.1；P 交互作用=0.10）。总体而言，膀胱癌风险与 GSTO2 Asn142Asp（纯合子；OR=1.4；95% CI：1.0-1.9；P 趋势=0.06）和 GSTZ1 Glu32Lys（纯合子；OR=1.3；95% CI：0.9-1.8；P 趋势=0.06）有关。我们的研究结果表明，膀胱癌的易感性可能与参与砷代谢和氧化应激反应的基因变异以及需要在其他人群中证实的潜在基因-环境相互作用有关。
