Adenocarinoma of the Lung in Women

女性肺腺癌

• 批准号: 6333825
• 负责人: Ann G. Schwartz
• 金额: $ 55.77万
• 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/6333825
• 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 而发病率，特别是腺癌的发病率在 女人。许多证据表明，在 对烟草致癌物的敏感性。多项研究表明，DNA 加合物、P53突变、肺组织细胞色素P4501A1表达和GSTM1缺失基因型 女性比男性更常见。差异化的原因 性别易感性可以用代谢酶的变化来解释。 功能或荷尔蒙的差异。一些相同的酶参与了 烟草烟雾中致癌物质的代谢参与了烟草的代谢。 雌激素。 这项拟议研究的目标有两个。首先，我们将评估这一角色 烟草烟雾和雌激素在确定前列腺癌风险中的作用 女性中的肺脏。其次，我们将评估雌激素受体和 C-erb B-2在肺肿瘤中的作用 雌激素可能在肺部起作用。具体目标是：1)开展一项 以人群为基础的烟草暴露的病例对照研究， 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例病例将通过大都会确诊 卡马诺斯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控件 正在拨号。2)确定代谢酶基因座CYP1A1的基因型， 细胞色素P4501B1、细胞色素P17、细胞色素P19、谷胱甘肽转移酶M1、谷胱甘肽转移酶1、COMT和NQO1与高血压风险相关。 女性的肺腺癌。这些酶在两种情况下都很活跃 烟草烟雾致癌物质的代谢及其合成代谢 雌激素。3)研究基因-基因和基因-环境的相互作用，重点 关于烟草和雌激素的影响。4)确定雌激素受体状态 (α和β)和c-erbB-2在肺癌患者肺肿瘤中的表达 腺癌，并评估与烟草暴露、雌激素相关的风险 肿瘤代谢酶基因座的使用、生育史和基因分型 特点。 拟议的研究代表了确定贡献的重点方法 基因和环境对女性肺腺癌风险的影响。这个 这项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。已经选择了哪些基因会影响 烟草致癌物质和雌激素在肺部的生物有效剂量。 对肿瘤特性的研究将为深入了解肿瘤的发病机制提供依据。 行动。这项以人群为基础的大型研究应该为重要的 肺癌的预防和治疗策略。