谷胱甘肽 S-转移酶 ω-1、砷甲基转移酶和亚甲基四氢叶酸还原酶的遗传变异、砷暴露与膀胱癌：一项病例对照研究。
Genetic variation in glutathione S-transferase omega-1, arsenic methyltransferase and methylene-tetrahydrofolate reductase, arsenic exposure and bladder cancer: a case-control study.
机构信息
Program of Population Studies and Disparities Research, Karmanos Cancer Institute, 4100 John R, Detroit, MI 48201, USA.
出版信息
Environ Health. 2012 Jun 29;11:43. doi: 10.1186/1476-069X-11-43.
BACKGROUND
Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer.
METHODS
Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a case-control study in Southeastern Michigan and exposed to low to moderate (<50 μg/L) levels of arsenic in their drinking water. A time-weighted measure of arsenic exposure was constructed using measures from household water samples combined with past residential history, geocoded and merged with archived arsenic data predicted from multiple resources.
RESULTS
While no single SNP in As3MT was significantly associated with bladder cancer overall, several SNPs were associated with bladder cancer among those exposed to higher arsenic levels. Individuals with one or more copies of the C allele in rs11191439 (the Met287Thr polymorphism) had an elevated risk of bladder cancer (OR = 1.17; 95% CI = 1.04-1.32 per 1 μg/L increase in average exposure). However, no association was observed between average arsenic exposure and bladder cancer among TT homozygotes in the same SNP. Bladder cancer cases were also 60% less likely to be homozygotes for the A allele in rs1476413 in MTHFR compared to controls (OR = 0.40; 95% CI = 0.18-0.88).
CONCLUSIONS
Variation in As3MT and MTHFR is associated with bladder cancer among those exposed to relatively low concentrations of inorganic arsenic. Further investigation is warranted to confirm these findings.
背景
摄入高浓度无机砷的地下水与不良健康后果有关，包括膀胱癌，但在较低浓度下，研究并未一致观察到任何风险升高。砷代谢和清除的遗传变异性是任何砷潜在健康风险研究的重要考虑因素。因此，我们研究了被认为在砷代谢中起作用的基因与膀胱癌之间的关联。
方法
使用来自密歇根州东南部参与病例对照研究的 219 例膀胱癌病例和 273 例对照的 DNA，对 GSTO-1、As3MT 和 MTHFR 中的单核苷酸多态性（SNP）进行基因分型，这些个体的饮用水中砷暴露水平较低至中等（<50μg/L）。使用家庭水样测量值结合过去的居住史构建了一个时间加权的砷暴露测量值，然后将其与存档的砷数据进行地理编码并合并，该数据是从多个资源预测得到的。
结果
尽管 As3MT 中的单个 SNP 与膀胱癌总体上无显著相关性，但在暴露于较高砷水平的人群中，有几个 SNP 与膀胱癌相关。与 rs11191439（Met287Thr 多态性）中的 C 等位基因的一个或多个拷贝的个体患膀胱癌的风险增加（OR=1.17；95%CI=1.04-1.32，每增加 1μg/L 平均暴露量）。然而，在相同 SNP 中，TT 纯合子的平均砷暴露与膀胱癌之间没有观察到关联。与对照组相比，MTHFR 中的 rs1476413 中的 A 等位基因的纯合子膀胱癌病例也减少了 60%（OR=0.40；95%CI=0.18-0.88）。
结论
在暴露于相对较低浓度无机砷的人群中，As3MT 和 MTHFR 的变异与膀胱癌相关。需要进一步研究来证实这些发现。
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