SNPs of GSTM1, T1, P1, epoxide hydrolase and DNA repair enzyme XRCC1 and risk of urinary transitional cell carcinoma in southwestern Taiwan
SNPs of GSTM1, T1, P1, epoxide hydrolase and DNA repair enzyme XRCC1 and risk of urinary transitional cell carcinoma in southwestern Taiwan
复制标题
DOI：
10.1016/j.taap.2007.12.003
复制
发表时间：
2008-04-15
影响因子：
3.8
通讯作者：
Chen, Chien-Jen
中科院分区：
文献类型：
--
作者：
Hsu, Ling-I;Chiu, Allen W.;Chen, Chien-Jen
摘要本研究在台湾西南地区黑足病（BFD）流行区附近进行医院病例对照研究，探讨泌尿行性细胞癌（TCC）可能的危险因素及遗传易感性。1998年至2002年间，共有221名病理证实的TCC患者和223名年龄性别匹配的泌尿科门诊患者被招募。结果显示，居住在BFD地区和饮用井水超过10年是影响尿癌风险的重要因素（优势比[OR]，8.16, 95%可信区间[CI]，3.34-19.90, p < 0.000 1）。井水中砷的平均浓度与TCC风险之间存在剂量反应关系。在本研究中，吸烟在泌尿系癌变中所起的作用相对较小。GSTP1 Ile105Val A -> G多态性与癌症风险显著相关（A/G + G/G: OR= 0.60, 95%CI = 0.39-0.94,p = 0.02）， Val 105等位基因的影响主要局限于55岁以下诊断的受试者（A/G + G/G: OR,0.29; 95%CI, 0.09-0.87, p = 0.03）。结果表明GSTP1是易感位点的候选位点，Ile 105等位基因可能使个体易患早发性尿TCC。GSTM1零基因型与高侵袭性肿瘤相关(OR,2.2; 95% CI, 1。34-4.73)以及早发性TCC风险（OR,2.53; 95% CI, 0.97-6.59）。我们的初步结果显示，XRCC1 Arg194Trp与砷相关性尿TCC相关，基因型与暴露之间的相互作用具有统计学意义。GSTM1、GSTT1、GSTP1 Ile105Val、EPHX Tyr113His和XRCC1 Arg280His对砷相关TCC风险的调节作用也提示。这些观察结果表明，致癌物质暴露的代谢受损以及DNA修复功能受损在砷相关的尿移行细胞癌发生中起重要作用。(C) 2007爱思唯尔公司版权所有。
A hospital-based case-control study was conducted near a former black-foot disease (BFD)-endemic area in southwestern Taiwan to examine the possible risk factors and genetic susceptibility for urinary transitional cell carcinoma (TCC). A total of 221 patients with pathologically confirmed TCC and 223 age-sex-matched control subjects from urology outpatient clinics were recruited between 1998 and 2002. The results showed that residency in the BFD area and consumption of well water for more than 10 years was a strong factor on urinary cancer risk (odds ratio [OR],8.16, 95% confidence interval [CI],3.34-19.90, p < 0.000 1). Dose response relationship between average arsenic concentration in well water and TCC risk was also observed. Cigarette smoking played a relatively minor role in urinary carcinogenesis in this study. The GSTP1 Ile105Val A -> G polymorphism was significantly associated with cancer risk (A/G + G/G: OR= 0.60, 95%CI = 0.39-0.94,p = 0.02), and the effect of Val 105 allele was largely confined to the subjects diagnosed earlier than 55 years old (A/G + G/G: OR,0.29; 95% CI, 0.09-0.87, p = 0.03). The results suggest that GSTP1 is a candidate for susceptibility locus and Ile 105 allele may predispose individuals to early-onset urinary TCC. The GSTM1 null genotype was associated with tumors of high-invasiveness (OR,2.2 1; 95% CI, 1. 34-4.73) as well as with early-onset TCC risk (OR,2.53; 95% CI, 0.97-6.59). Our preliminary results showed the XRCC1 Arg194Trp were associated with arsenic-related urinary TCC and the interaction between the genotype and the exposure was statistically significant. The modulating effect of the GSTM1, GSTT1, GSTP1 Ile105Val, EPHX Tyr113His and XRCC1 Arg280His on arsenic-related TCC risk was also suggestive. These observations implied that impaired metabolism of carcinogenic exposure as well as impaired DNA repair function play an important role in arsenic-related urinary transitional cell carcinogenesis. (C) 2007 Elsevier Inc. All rights reserved.