Cao Wei, Cai Lin, Rao Jian-Yu, Pantuck Allan, Lu Ming-Lan, Dalbagni Guido, Reuter Victor, Scher Howard, Cordon-Cardo Carlos, Figlin Robert A, Belldegrun Arie, Zhang Zuo-Feng
Department of Epidemiology, UCLA School of Public Health, and Jonsson Comprehensive Cancer Center, Los Angeles, California 90095-1772, USA.
Cancer. 2005 Dec 1;104(11):2400-8. doi: 10.1002/cncr.21446.
Although cigarette smoking is considered a major risk factor for bladder carcinoma, little is known about the interaction between metabolic genes such as glutathione-S-transferase P1 and tobacco smoking in this process. GSTP1 may play a role in detoxification of tobacco-related carcinogens.
In this case-control study of 145 cases with bladder carcinoma (male:female = 7.5:1) and 170 noncancer controls (male:female = 3.7:1), the relation between genetic polymorphisms of GSTP1 and susceptibility to bladder carcinoma was investigated and the gene-environment interaction between tobacco smoking and GSTP1 polymorphism was evaluated. Epidemiological data were collected for all cases and controls by a standard questionnaire. Polymorphisms of GSTP1 were measured by polymerase chain reaction-restriction fragment length polymorphism. The logistic regression model in SAS was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).
Cigarette smoking was confirmed as a risk factor of bladder carcinoma with an OR of 3.1 (95% CI: 1.7-5.9) after controlling for potential confounding factors. The OR for pack-years of smoking as a continuous variable was 2.4 (95% CI: 2.0-2.8). The ORs were 7.6 (95% CI: 1.18-49.51) for isoleucine/valine (Ile/Val) and 6.5 (95% CI: 1.01-41.56) for Ile/Ile when the homozygous Val/Val was considered as comparison group after adjusting for age, gender, race, and education. The adjusted OR for interaction between smoking and the GSTP1 (any Ile genotype) was 11.42 (95% CI: 0.53-248.15).
The results indicate that the Ile 105 allele is associated with an increased risk of bladder carcinoma and suggest that individuals who smoke and possess the Ile allele might be at increased risk for bladder carcinoma.
尽管吸烟被认为是膀胱癌的主要危险因素，但在此过程中，关于谷胱甘肽 - S - 转移酶P1等代谢基因与吸烟之间的相互作用知之甚少。GSTP1可能在烟草相关致癌物的解毒过程中发挥作用。
在这项病例对照研究中，纳入了145例膀胱癌患者（男性∶女性 = 7.5∶1）和170例非癌对照者（男性∶女性 = 3.7∶1），研究了GSTP1基因多态性与膀胱癌易感性之间的关系，并评估了吸烟与GSTP1多态性之间的基因 - 环境相互作用。通过标准问卷收集所有病例和对照者的流行病学数据。采用聚合酶链反应 - 限制性片段长度多态性方法检测GSTP1的多态性。使用SAS中的逻辑回归模型估计比值比（OR）和95%置信区间（95%CI）。
在控制潜在混杂因素后，吸烟被确认为膀胱癌的危险因素，OR为3.1（95%CI：1.7 - 5.9）。吸烟包年数作为连续变量的OR为2.4（95%CI：2.0 - 2.8）。在调整年龄、性别、种族和教育程度后，以纯合子Val/Val作为对照组时，异亮氨酸/缬氨酸（Ile/Val）的OR为7.6（95%CI：1.18 - 49.51），Ile/Ile的OR为6.5（95%CI：1.01 - 41.56）。吸烟与GSTP1（任何Ile基因型）之间相互作用的调整后OR为11.42（95%CI：0.53 - 248.15）。
结果表明，Ile 105等位基因与膀胱癌风险增加相关，提示吸烟且携带Ile等位基因的个体患膀胱癌的风险可能增加。
