PILOT--SOMATIC ERRORS IN CARCINOGEN METABOLISM

基因决定的代谢致癌物和 致癌原是多态的。因为由此产生的差异 环境化学品的解毒和/或活化 致癌物与致癌物之间的关系，这些基因的多态与 易患与环境有关的癌症，如鳞状细胞癌 头颈部癌。 我们的假设是：(I)遗传多态可以通过 关于谷胱甘肽S转移酶u、theta、pi和N-乙酰化，AS 以及细胞色素P450系统的组成成分(细胞色素P4501A1、细胞色素P2E1A1)。 口腔鳞状细胞癌患者的临床表现 口咽部与健康对照组的比较，以及(Ii)这些基因 基因多态与这类疾病的发病风险有关。 癌症。 在一项对42名头颈部癌症患者和42名配对患者进行的初步研究中 对照我们发现，GSTM1基因的缺失会导致 比值为3.10(95%CI=1.24-7.75)，GSTT1基因缺失 头部和颈部的优势比为2.18(95%CI=0.91-5.23 癌症。相比之下，在我们的患者中，74%的患者GSTM1基因缺失 在公布的31-58%的范围内。显示GSTT1基因缺失。 在我们55%的患者中，与公布的30-40%的范围相反。 提出了一项病例对照研究，涉及250名患者和250名健康人。 个人(与年龄、性别、种族和吸烟状况相匹配)。这个 研究对象的遗传状态将根据以下方面确定 谷胱甘肽S-转移酶u，theta和pi，N-乙酰化，细胞色素P1A1，和 使用从外周血细胞中提取的DNA，采用基于聚合酶链式反应的方法 血淋巴细胞(特异性目标1)。两种方法将适用于 估计癌症风险。首先，风险和遗传基因之间的联系 将为所分析的每个多态计算多态(特定 目标2)。接下来，这一单因素分析将通过结合 将基因分型纳入多因素风险模型(具体目标3)。这个 预计这项研究将提供有关猪瘟宿主因素的重要信息 与环境相关的致癌作用。检测几种基因 多态同时具有识别个体的潜力 癌症风险极高。这具有深远的影响， 预防：癌症高危人群可参加 不适合普通人群的密集预防计划， 包括化学预防方法。

The genetically determined ability to metabolize carcinogens and procarcinogens is polymorphic. Because of the resulting differences in detoxification of environmental chemicals and/or in activating procarcinogens to carcinogens, these polymorphisms are associated with susceptibility to environmentally-related cancers, such as squamous cell carcinoma of the head and neck. Our hypotheses are that (i) genetic polymorphisms can be detected with regard to glutathione S-transferases mu, theta, pi, and N-acetylation, as well as to components of the cytochrome P450 system (CYP1A1, CYP2E1) in patients with squamous cell carcinoma of the oral cavity and the oropharynx compared to healthy controls, and (ii) these genetic polymorphisms are associated with risk for the development of this type of cancer. In a pilot study of 42 head and neck cancer patients and 42 matched controls we found that the absence of the GSTM1 gene conferred an odds ratio of 3.10 (95% CI=1.24-7.75), and the absence of the GSTT1 gene conferred an odds ratio of 2.18 (95% CI=0.91-5.23) for head and neck cancer. The GSTM1 genotype was absent in 74% of our patients, in contrast to the range of 31-58% published. The absence of the GSTT1 gene was shown in 55% of our patients, in contrast to the published range of 30-40%. A case-control study is proposed, involving 250 patients and 250 healthy individuals (matched by age, gender, race, and smoking status). The genetic status of the study subjects will be determined with regard to glutathione S-transferases mu, theta, and pi, N-acetylation, CYP1A1, and CYP2E1 by PCR-based methodologies, using DNA extracted from peripheral blood lymphocytes (Specific Aim #1). Two approaches will be applied for estimating cancer risk. First, the associations between risk and genetic polymorphisms will be calculated for each polymorphism assayed (Specific Aim #2). Next, this single-factor analysis will be expanded by combining the genotypes into a multifactorial risk model (Specific Aim #3). The study is expected to yield important information about host factors of environmentally-associated carcinogenesis. Testing several genetic polymorphisms simultaneously has the potential to identify individuals with extremely high cancer risk. This has profound implications for prevention: individuals at high risk for cancer can be enrolled into intensive preventive programs not suitable for the general population, including chemopreventive approaches.