Adenocarinoma of the Lung in Women

女性肺腺癌

• 批准号: 6752126
• 负责人: Ann G. Schwartz
• 金额: $ 61.45万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-13 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6752126
• 关键词: adenocarcinoma; cancer risk; clinical research; cytochrome P450; disease /disorder etiology; estrogen receptors; estrogens; female; gene environment interaction; gene interaction; glutathione transferase; hormone regulation /control mechanism; hormone related neoplasm /cancer; human subject; lung neoplasms; methyltransferase; neoplasm /cancer epidemiology; neoplasm /cancer genetics; parity; passive smoking; protooncogene; smoking; steroid hormone metabolism; tobacco abuse

DESCRIPTION: In 1998, 80,000 women in the US were diagnosed with lung cancer and incidence rates, particularly of adenocarcinoma, continue to increase among women. Many pieces of evidence suggest that there are gender differences in susceptibility to tobacco carcinogens. Several studies have shown that DNA adducts, p53 mutations, CYP1A1 expression in the lung, and GSTM1 null genotypes are more frequent in females than in males. Reasons for differential susceptibility by gender might be explained by variations in metabolic enzyme functioning or hormonal differences. Some of the same enzymes involved in the metabolism of carcinogens in tobacco smoke are involved in the metabolism of estrogen. The goals of the proposed study are two-fold. First, we will evaluate the role of tobacco smoke and estrogens in determining risk of adenocarcinoma of the lung among women. Secondly, we will evaluate the role of estrogen receptors and c-erbB-2 in lung tumors to further understand the pathways through which estrogen may be acting in the lung. The specific aims are: 1) To conduct a population-based case-control study of the contribution of tobacco exposure, estrogen use, and reproductive history in determining risk of adenocarcinoma of the lung in women. 716 cases will be identified through the Metropolitan Detroit Cancer Surveillance System of the Karmanos Cancer Institute (a SEER participant). An equal number of controls will be selected through random digit dialing. 2) To determine if genotype at the metabolic enzyme loci CYP1A1, CYP1B1, CYP17, CYP19, GSTM1, GSTP1, COMT, and NQO1 are associated with risk of adenocarcinoma of the lung in women. These enzymes are active in both the metabolism of tobacco smoke carcinogens and the synthesis and metabolism of estrogens. 3) To examine gene-gene and gene-environment interactions, focusing on tobacco and estrogen effects. 4) To determine estrogen receptor status (alpha and beta) and c-erbB-2 levels in the lung tumors of women with adenocarcinoma and evaluate risk associated with tobacco exposure, estrogen use, reproductive history, and genotype at metabolic enzyme loci by tumor characteristics. The proposed study represents a focused approach to defining the contribution of genes and environments in risk of adenocarcinoma of the lung in women. The interview component of the study will provide data about individually measured environmental risk factors. Genotypes have been chosen which impact on biologically effective dose of tobacco carcinogens and estrogens in the lung. The study of tumor characteristics will provide insight into mechanism of action. This large, population-based study should provide clues for important prevention and therapeutic strategies for lung cancer.

描述：1998年，美国有8万名妇女被诊断出患有肺癌。 和发病率，特别是腺癌，继续增加， 妇女许多证据表明，在性别方面存在差异。 对烟草致癌物的敏感性。一些研究表明，DNA 加合物、p53突变、肺中CYP 1A 1表达和GSTM 1缺失基因型 女性比男性更常见。差异原因 性别易感性可以用代谢酶的变化来解释 功能或荷尔蒙差异。一些参与细胞凋亡的酶 烟草烟雾中致癌物质的代谢参与了 雌激素. 拟议的研究有两个目标。首先，我们将评估 吸烟和雌激素在确定乳腺癌风险中的作用 女性的肺。其次，我们将评估雌激素受体的作用， c-erbB-2在肺肿瘤中的作用，以进一步了解 雌激素可能作用于肺。具体目标是：（1）开展 基于人群的烟草暴露影响的病例对照研究， 雌激素使用和生殖史在确定乳腺癌风险中的作用 女性的肺716例将通过大都会确定 Karmanos癌症研究所底特律癌症监测系统（SEER 参与者）。将通过随机数字选择相同数量的对照品 正在拨号2)为了确定代谢酶基因座CYP 1A 1的基因型， CYP 1B 1、CYP 17、CYP 19、GSTM 1、GSTP 1、COMT和NQO 1与以下风险相关： 女性肺腺癌。这些酶在两种组织中都有活性， 烟草烟雾致癌物的代谢及 雌激素类。3)为了研究基因-基因和基因-环境的相互作用， 烟草和雌激素的影响4)确定雌激素受体状态 女性肺癌患者的α和β-erbB-2水平 腺癌和评估风险与烟草暴露，雌激素 按肿瘤列出的使用、生殖史和代谢酶位点基因型 特色 拟议的研究是一种重点明确的方法， 基因和环境在女性肺腺癌风险中的作用的 研究的访谈部分将提供有关个人测量的数据， 环境风险因素。选择的基因型影响 烟草致癌物和雌激素在肺中的生物有效剂量。 对肿瘤特性的研究将有助于深入了解肿瘤的发生机制， 行动上这项大型的、基于人群的研究应该为重要的 肺癌的预防和治疗策略。