METABOLIC EPIDEMIOLOGY OF TOBACCO RELATED CANCERS IN BLACK AND WHITE AMERICANS

描述：(申请人描述)美国的非裔美国人和高加索人表现出明显不同的烟草相关肿瘤特征。对这些群体的吸烟模式的分析并没有显示出每天更高的香烟摄入量，以解释观察到的非裔美国人更高的空气消化系统癌症患病率，或者更喜欢的烟草产品类型的差异，这可能有助于解释为什么观察到的黑人膀胱癌发病率较低。目前的建议是我们代谢流行病学研究的继续和延伸，旨在阐明代谢能力的差异是否导致个人和靶组织对活性烟草烟雾致癌物暴露的差异是导致观察到的特定部位癌症发病率变化的原因。拟议的五年调查将包括四项主要研究。在研究A中，总共招募了320名健康吸烟者，每种种族和性别组合中的80人。在这项以社区为基础的横断面研究中，将获得关于生活方式、吸烟史和饮食的问卷数据。此外，还将研究几个新的烟草致癌物暴露和易感性的生物标志物，包括4-氨基联苯血红蛋白加合物、NNK和PAH尿代谢物，以及参与烟草致癌物代谢的酶GSTM1、CYP1A1和CYP2E1以及DNA修复酶O6-烷基鸟嘌呤-DNA烷基转移酶(AGT-1)的基因多态性。在研究B中，将在140例患者和匹配的对照组中调查NNAL-葡萄糖醛酸化表型、PAH暴露和代谢生物标志物与肺癌风险的关系。在研究C中，一项更大规模的病例对照研究(每组1175名受试者)将检查致癌物代谢和DNA修复基因型与肺癌风险之间的关系。最后，在研究D中，将采用病例对照设计，每组140名受试者，在非裔美国人和高加索人中调查乙酰化基因和其他选定的膀胱癌风险生物标记物的相关性。总体而言，该项目试图提供机制，从而阐明不同种族之间特定部位癌症发病率的差异，并借鉴这一综合计划的项目2和4以及美国健康基金会的烟草相关癌症大型数据库的结果。代谢流行病学的独特方法，将适当的问卷数据与从不同人群获得的实验室结果相结合，将使我们能够更充分地了解观察到的癌症患病率的多样性。

DESCRIPTION: (Applicant's Description) African American and Caucasian populations in the United States manifest distinctly different profiles of tobacco-related neoplasms. Analyses of smoking patterns by these groups have not revealed a higher intake of cigarettes per day to account for the observed higher prevalence of aerodigestive cancer among African Americans, or differences in type of tobacco products preferred, which might help explain the observed lower rates of urinary bladder cancer among blacks. The current proposal is a continuation and extension of our metabolic epidemiological study designed to elucidate whether differences in metabolic capacity resulting in differences in exposure of individuals and target tissues to activated tobacco smoke carcinogens are responsible for the observed variations in site-specific cancer incidence. The proposed five-year investigation will consist of four major studies. In Study A, a total of 320 healthy smokers, 80 of each race-sex combination will be recruited. In this community-based cross-sectional study, questionnaire data on lifestyle, smoking history and diet will be obtained. In addition, several new biomarkers for exposure and susceptibility to tobacco-smoke carcinogens will be studied including 4-aminobiphenyl hemoglobin adducts, NNK and PAH urinary metabolites, and genetic polymorphisms in genes coding for enzymes involved in tobacco-smoke carcinogen metabolism including GSTM1, CYP1A1 and CYP2E1, and the DNA repair enzyme, O6-alkylguanine-DNA alkyltransferase (AGT-1). In Study B, the relationship between NNAL-glucuronidation phenotype, PAH exposure and metabolism biomarkers and risk for lung cancer will be investigated in 140 cases and matched controls. In Study C, a larger-scale case-control study (1175 subjects per group), the relationship between carcinogen metabolism and DNA repair genotypes and lung cancer risk will be examined. Finally, in Study D, the association of acetylation genotype and other selected biomarkers of bladder cancer risk will be investigated in African Americans and Caucasians using a case-control design with 140 subjects per group. Overall, this project attempts to provide mechanisms whereby differences in site-specific cancer incidence between the races are elucidated and draws upon the results from Projects 2 and 4 of this integrated program and the American Health Foundation's large data base of tobacco-related cancers. The unique approach in metabolic epidemiology, combining appropriate questionnaire data with laboratory results obtained from diverse populations, will enable us to more fully understand the observed diversity in cancer prevalence.