GENETIC RISK AND CARCINOGEN EXPOSURE - A COMMON INHERITED DEFECT OF THE CARCINOGEN-METABOLISM GENE GLUTATHIONE-S-TRANSFERASE M1 (GSTM1) THAT INCREASES SUSCEPTIBILITY TO BLADDER-CANCER
GENETIC RISK AND CARCINOGEN EXPOSURE - A COMMON INHERITED DEFECT OF THE CARCINOGEN-METABOLISM GENE GLUTATHIONE-S-TRANSFERASE M1 (GSTM1) THAT INCREASES SUSCEPTIBILITY TO BLADDER-CANCER
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DOI：
10.1093/jnci/85.14.1159
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发表时间：
1993-07-21
期刊：
影响因子：
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通讯作者：
LUCIER, GW
中科院分区：
文献类型：
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作者：
BELL, DA;TAYLOR, JA;LUCIER, GW
背景：大量研究表明膀胱癌与暴露于烟草烟雾和其他环境或职业暴露中的致癌物有关。大约50%的人类遗传了两个缺失的GSTM1基因拷贝，该基因编码致癌解毒酶谷胱甘肽s -转移酶M1。最近的研究表明，GSTM1基因可能调节环境致癌物的内剂量，从而影响膀胱癌的发生风险。目的：研究GSTM1基因缺失是否影响膀胱癌风险，以及GSTM1基因型频率是否存在种族差异。方法：采用基于聚合酶链反应（PCR）的方法，对来自杜克大学医学中心和北卡罗莱纳大学医院泌尿外科诊所的229例膀胱移行细胞癌患者和211例对照患者的纯合缺失基因型（GSTM1 0/0）的频率进行了检测。对照对象为泌尿科临床患者，主要表现为良性前列腺肥大或阳痿，除非黑色素瘤皮肤癌外无其他癌症病史，在种族、性别和年龄（10岁间隔）上与病例患者频率匹配。为了探索GSTM1基因频率的种族差异，研究人员还对来自北卡罗来纳州达勒姆和教堂山的466名有偿、健康、无血缘关系的志愿者进行了基因型检测。GSTM1基因位点的存在与否通过差异PCR（一种多基因共扩增的半定量技术）来确定。结果：总体而言，GSTM1 0/0基因型使膀胱癌风险增加70%（优势比[OR] = 1.7； 95%可信区间[CI] = 1.2-2.5; P = 0.004）。编码谷胱甘肽s -转移酶M1酶的GSTM1基因缺失显著增加了暴露于烟草烟雾致癌物的人的风险（OR = 1.8; 95% CI = 1.2-3.0; P = 0.01），但对没有暴露于烟草烟雾致癌物的人的风险几乎没有增加。具有GSTM1 0/0基因型的吸烟暴露超过50包年的人的风险比最低风险组（即GSTM1 +/+或+/0的非吸烟者）的人高6倍。在合并临床对照和社区样本组（677人）中，GSTM1 0/0基因型在黑人（35%）中的发生率低于白人（49%）
Background: Numerous studies have associated bladder cancer with exposure to carcinogens present in tobacco smoke and other environmental or occupational exposures. Approximately 50% of all humans inherit two deleted copies of the GSTM1 gene which encodes for the carcinogen-detoxification enzyme glutathione S-transferase M1. Recent findings suggest that the GSTM1 gene may modulate the internal dose of environmental carcinogens and thereby affect the risk of developing bladder cancer. Purpose: We investigated whether the absence of the GSTM1 gene affects bladder cancer risk and whether there are racial differences in GSTM1 genotype frequency. Methods: Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the homozygous deleted genotype (GSTM1 0/0) in 229 patients with transitional cell carcinoma of the bladder and 211 control subjects who were enrolled from the Urology Clinics at Duke University Medical Center and the University of North Carolina Hospitals. Control subjects were urology clinic patients who primarily presented with benign prostatic hypertrophy or impotence, who had no history of any cancer other than nonmelanoma skin cancer, and who were frequency matched to case patients on race, sex, and age (10-year age intervals). In order to explore racial differences in GSTM1 gene frequency, genotype was also determined in a community-based sample of 466 paid, healthy, unrelated volunteers from Durham and Chapel Hill, N.C. The presence or absence of the GSTM1 gene locus was determined by using a differential PCR, a semiquantitative technique in which multiple genes are coamplified. Results: Overall, the GSTM1 0/0 genotype conferred a 70% increased risk of bladder cancer (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.2-2.5; P = .004). Absence of the GSTM1 gene encoding the glutathione S-transferase M1 enzyme significantly increased risk to persons with exposure to the carcinogens in tobacco smoke (OR = 1.8; 95% CI = 1.2-3.0; P = .01) but poses little increased risk to persons without such exposure. Persons with smoking exposure of more than 50 pack-years who had the GSTM1 0/0 genotype had a sixfold greater risk relative to persons in the lowest risk group (i.e., nonsmokers who were GSTM1 +/+ or +/0). In the pooled clinic control and community sample groups (677 individuals), the GSTM1 0/0 genotype occurred less frequently among Blacks (35%) than among Whites (49%, P