METABOLIC EPIDEMIOLOGY OF TOBACCO RELATED CANCERS IN BLACK AND WHITE AMERICANS

描述：（申请人描述）美国非裔美国人和白种人在烟草相关肿瘤方面表现出明显不同的特征。这些研究小组对吸烟模式的分析并没有揭示出非裔美国人每天摄入更多的香烟来解释观察到的更高的空气消化癌患病率，或者偏爱的烟草产品类型的差异，这可能有助于解释观察到的黑人中较低的膀胱癌发病率。目前的建议是我们的代谢流行病学研究的延续和延伸，旨在阐明代谢能力的差异导致个体和靶组织暴露于活化烟草烟雾致癌物的差异是否导致了观察到的部位特异性癌症发病率的变化。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，每种种族性别各80名。在这个以社区为基础的横断面研究中，将获得生活方式、吸烟史和饮食方面的问卷数据。此外，还将研究几种新的烟草烟雾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尿液代谢产物，以及与烟草烟雾致癌物代谢有关的酶编码基因的遗传多态性，包括GSTM1、CYP1A1和CYP2E1，以及DNA修复酶o6 -烷基鸟嘌呤-DNA烷基转移酶（AGT-1）。在研究B中，将在140例病例和匹配对照中研究nnal -葡萄糖醛酸化表型、多环烃暴露和代谢生物标志物与肺癌风险之间的关系。Study C是一项更大规模的病例对照研究（每组1175人），将研究致癌物代谢和DNA修复基因型与肺癌风险之间的关系。最后，在研究D中，乙酰化基因型和其他选定的膀胱癌风险生物标志物的关联将在非裔美国人和白种人中进行研究，采用病例对照设计，每组140名受试者。总的来说，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，并利用该综合项目的项目2和项目4以及美国健康基金会烟草相关癌症的大型数据库的结果。代谢流行病学的独特方法，将适当的问卷调查数据与从不同人群中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.