Serum Levels of EGFR-Signaling-Network Activators/Inhibitor and Lung Cancer Risk

描述(申请人提供)：尽管吸烟是肺癌的主要原因，但我们对其病因的认识仍然存在许多空白，被认为是因吸烟状况、性别和组织亚型而异的。这项来自妇女健康倡议(WHI)队列的1,384例肺癌病例和1,601例对照的嵌套病例对照研究的目的是阐明这些个体亚组中肺癌的危险因素。我们将集中于激活5种生理因子(IGF-I、HGF、NGF、胰岛素和IL-6)和1种抑制表皮生长因子受体(EGFR)信号网络的因子(IGFBP-3)的血清水平，该信号网络包括调节细胞增殖、存活和迁移的多条途径。我们将检查这6种激活物/抑制物的血清水平是否与肺癌风险有关，以及这种相关性是否因吸烟状况和组织亚型而异。此外，先前发现的EGFR信号网络中与肺癌相关的基因变异也将被纳入评估EGFR信号网络中的血清学和遗传因素如何相互作用来影响肺癌风险。庞大的WHI队列为研究女性亚组肺癌的异质性病因提供了宝贵的机会。识别吸烟者的易感因素和从不吸烟者的危险因素将有助于我们了解女性的健康，也可能为制定针对女性的肺癌预防计划提供见解。 公共卫生相关性：这项研究将在绝经后妇女中检查6种激活/抑制表皮生长因子受体(EGFR)信号网络的生理因子的血清水平是否与吸烟者和非吸烟者患肺癌的风险有关。由于从不吸烟的女性的肺癌发病率明显高于男性，阐明女性从不吸烟的危险因素将有助于我们了解女性的健康。确定吸烟者的宿主易感因素将有助于集中开展化学预防研究。这项研究也可能为肺癌的治疗管理提供见解。如果这些血清学因子的水平与肺癌的发病机制有关，那么检测和改变它们的异常水平可能是肺癌的一种替代治疗和化学预防策略。

DESCRIPTION (provided by applicant): Although smoking is the major cause of lung cancer, there remains many gaps in our knowledge of its etiology, which is thought to be heterogeneous by smoking status, gender, and histological subtype. The purpose of this nested case-control study with 1,384 lung cancer cases and 1,601 controls from the Women's Health Initiative (WHI) cohort is to elucidate the risk factors of lung cancer in these individual subgroups. We will focus on the serum levels of 5 physiological factors (IGF-I, HGF, NGF, insulin, and IL-6) that activate and one factor (IGFBP-3) that inhibits the epidermal growth factor receptor (EGFR) signaling network, which encompasses multiple pathways regulating cell proliferation, survival, and migration. We will examine if serological levels of the 6 activators/inhibitor are associated with risk of lung cancer, and whether the associations vary depending on smoking status and histological subtype. In addition, previously identified genetic variations in the EGFR signaling network that are associated with lung cancer will also be incorporated to assess how serological and genetic factors in the EGFR signaling network may interact to affect lung cancer risk. The large WHI cohort provides a valuable opportunity to study the heterogeneous etiology of lung cancers in subgroups of women. Identifying susceptibility factors in smokers and risk factors in never- smokers will contribute towards our understanding of women's health and may also provide insights into the development of lung cancer prevention programs for women. PUBLIC HEALTH RELEVANCE: This study will examine, in postmenopausal women, if serum levels of 6 physiological factors that activate/inhibit the epidermal growth factor receptor (EGFR) signaling network are associated with risk of lung cancer in smokers and non-smokers. As the incidence of lung cancer in never-smokers is significantly higher in women than men, elucidating the risk factors in female never-smokers would contribute towards our understanding of women's health. Identifying the host susceptibility factors in smokers would help to focus chemoprevention studies. This study may also provide insights into the therapeutic management of lung cancer. If the levels of these serological factors are involved in the pathogenesis of lung cancer, then testing for and modifying their aberrant levels could be an alternative treatment as well as a chemoprevention strategy for lung cancer.