Lung cancer molecular markers by sex: intergroup study

描述(由申请人提供)：我们建议在男性和女性肺癌患者中进行一项病例系列研究，调查易感性、生物有效剂量和肿瘤组织变化的分子标志物。这些标志物将根据主动和被动吸烟暴露、职业暴露以及生殖和激素因素的暴露数据进行评估，以阐明吸烟和不吸烟妇女肺癌，特别是腺癌增加的原因。为了优化我们招收患有肺癌的非吸烟者的能力，我们将与西南肿瘤学小组的肺委会调查人员和NCI肺科小组的合作成员合作，识别大量的肺癌患者，招募120名从不吸烟的肺癌女性和同等数量的男性，以及200名从不吸烟的女性和男性。我们有两个主要假设：根据代谢变异性，女性因对烟草致癌物质的易感性而处于更高的风险。我们认为，环境和遗传危险因素(DNA加合物)的相互作用以及肿瘤组织中的基因变化(P53和KRAS突变)的标记将反映男性和女性、吸烟者和不吸烟者之间暴露和易感性的差异，并将阐明不同性别和吸烟状况在风险方面的不成比例差异。我们的第二个假设是，似乎在肺癌发生中起作用的类固醇激素对女性的影响将大于男性，对从不吸烟的人比对吸烟者的影响更大。我们预测，肿瘤HER2扩增和雌激素受体将因性别和吸烟状况而异，特别是与环境和遗传(致癌物和类固醇激素代谢途径中的SNPs)危险因素有关。暴露、敏感性和效应的生物标志物将在这些患有肺癌的女性和男性患者的血液和肿瘤组织中进行分析，并结合调查问卷数据进行评估，以验证所提出的假设。这项研究是迄今为止评估易感性和疗效的生物标志物的最大规模的研究结果，可能会阐明吸烟和不吸烟女性肺癌，特别是腺癌上升的原因。

DESCRIPTION (provided by applicant): We propose to conduct a case-series study in men and women with lung cancer, investigating molecular markers of susceptibility, biologically effective dose, and tumor tissue alterations. These markers will be evaluated in relation to exposure data on active and passive smoke exposure, occupational exposures and reproductive and hormonal factors, in order to elucidate reasons for the increase in lung cancer, particularly adenocarcinoma, in both smoking and non-smoking women. To optimize our capabilities to enroll nonsmokers with lung cancer, we will work with the Lung Committee investigators of the Southwest Oncology Group and collaborating members of the NCI lung intergroup to identify large numbers of patients with lung cancer, enrolling 120 never-smoking women with lung cancer and an equal number of males, as well as 200 each of ever smoking females and males. We have two primary hypotheses: that women are at higher risk due to susceptibility to tobacco-smoke carcinogens, based on metabolic variability. We propose that markers of the interactions of environmental and genetic risk factors for lung cancer (DNA adducts), as well as genetic alterations in tumor tissue (p53 and kras mutations), will reflect differences in exposures and susceptibility between men and women, smokers and non-smokers, and will elucidate the disproportionate variability in risk by gender and smoking status. Our second hypothesis is that steroid hormones, which appear to play a role in lung carcinogeneis, will have a greater effect in women than in men and in never smokers rather than smokers. We predict that tumor HER2 amplification and estrogen receptors will vary by gender and smoking status, particularly in relation to environmental and genetic (SNPs in carcinogen and steroid hormone metabolism pathways) risk factors. Biomarkers of exposure, susceptibility, and effect will be assayed in the blood and tumor tissue of these women men with lung cancer and evaluated in relation to questionnaire data to test the proposed hypotheses. Results from this study, the largest to date to evaluate biomarkers of susceptibility and effect, will likely elucidate reasons for the rise in lung cancer, particularly adenocarcinomas, in smoking and non-smoking women.