MOLECULAR EPIDEMIOLOGY OF OCCUPATIONAL BLADDER CANCER

职业性膀胱癌的分子流行病学

• 批准号: 3491417
• 负责人: GERALD M. LOWER
• 金额: $ 3.86万
• 依托单位: BC RESEARCH
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1986-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3491417
• 关键词: Japanese; N acylation; acetyl coA acetyltransferase; acetylation; bladder neoplasm; cancer risk; chemical carcinogen; chemical related neoplasm /cancer; cyclic amine; detoxification; dyes; environment related neoplasm /cancer; gene expression; human population genetics; human subject; naphthylamine; neoplasm /cancer genetics; occupational hazard

A variable but often significant proportion of urinary bladder cancer can be attributed to occupational and cultural (smoking) situations associated with exposures to carcinogenic arylamines. The variable N-acetylation of carcinogenic arylamines by human hepatic enzyme systems, the known genetic regulation and polymorphic distribution of this enzyme activity in humans, and the known enhanced susceptibility of individuals with the genetically-distinct "slow acetylator" phenotype to various arylamine toxicities, has prompted examination of possible correlations between human-N-acetyltransferase phenotype and susceptibility to urinary bladder cancer. The hypothesis being tested is that slow acetylators, by virtue of their lesser abilities to detoxify arylamines by N-acetylation, might be more susceptible to occupation- and smoking-related urinary bladder cancer and might, therefore, be found in greater percentage in bladder cancer populations than in nationality-matched, disease-free control populations. Sulfamethazine phenotyping will be employed to examine well defined Japanese bladder cancer populations with and without histories of cigarette smoking, and with and without documentable occupational exposure to 4,4'-diamino-biphenyl (i.e., benzidine) or 2-aminophthalene (i.e., beta-naphthylamine). The results of these studies are expected to allow assessment of the existence of a relationship between arylamine-induced bladder cancer and the slow acetylator phenotype as a determinant of susceptibility, assessment of the involvement of arylamines in tobacco smoke-related bladder cancer, and assessment of the feasibility of identifying highly susceptible individuals in high risk populations.

一种可变但往往相当大比例的膀胱癌可以 归因于相关的职业和文化(吸烟)情况 暴露在致癌芳胺中。可变型N-乙酰化 人类肝酶系统致癌的芳胺，已知的基因 这种酶活性在人类体内的调节和多态分布， 以及已知的增强的个体易感性 不同芳香胺的遗传不同的“慢乙酰化”表型 毒性，促使人们研究两者之间可能的相关性 人-N-乙酰基转移酶表型与膀胱易感性的关系 癌症。 正在测试的假设是，慢乙酰化者，凭借他们的 通过N-乙酰化来解毒芳胺的能力较弱，可能更多 易患与职业和吸烟有关的膀胱癌和 因此，在膀胱癌中发现的比例可能更高 与国籍匹配、无疾病控制的人群相比，这一比例更高。 将使用磺胺二甲嘧啶表型来检查明确定义的 有吸烟史和无吸烟史的日本膀胱癌人群 吸烟，并有或没有可记录的职业暴露于 4，4‘-二氨基联苯(即联苯胺)或2-氨基苯基(即， β-萘胺)。 预计这些研究的结果将有助于评估 芳胺诱发膀胱癌与膀胱癌的关系 慢乙酰化表型作为易感性的决定因素， 与烟草烟雾相关的芳胺类物质的评估 膀胱癌，以及高度鉴别的可行性评估 高危人群中的易感个体。