Sex Hormones, Phytoestrogens and Lung Cancer in Female Nonsmokers

女性非吸烟者的性激素、植物雌激素和肺癌

• 批准号: 9007349
• 负责人: Gong Yang
• 金额: $ 12.28万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2016-04-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9007349
• 关键词: Accounting; Address; Adult; Affect; Androgens; Androstenedione; Aromatase; Blood; Blood specimen; Cancer Etiology; Cancer Patient; Carcinogens; Cessation of life; Chinese People; Clinical Trials; Cohort Studies; Consumption; Development; Diet; Dietary Assessment; Dietary Component; Dietary intake; Disease; Eating; Estradiol; Estrogen Antagonists; Estrogens; Estrone; Etiology; Evaluation; Exposure to; Female; Funding; Genistein; Gonadal Steroid Hormones; Hormone replacement therapy; Intake; Isoflavones; Knowledge; Lead; Low Prevalence; Lung; Malignant neoplasm of lung; Measures; Methods; Nested Case-Control Study; Participant; Passive Smoking; Phytoestrogens; Pilot Projects; Plants; Plasma; Play; Post-Menopausal Hormone Replacement Therapy; Postmenopause; Prevention strategy; Risk; Risk Factors; Role; Sampling; Soy Foods; Tamoxifen; Testosterone; Tissues; Tobacco; Tobacco use; United States; Urine; Woman; Women' s Health; base; cancer risk; cigarette smoking; cohort; design; estrogenic activity; follow-up; glycitein; hormone therapy; liquid chromatography mass spectrometry; lung carcinogenesis; malignant breast neoplasm; member; mortality; non-smoker; novel; population based; prospective; public health relevance; soy; soy protein isolate; study population; urinary

 DESCRIPTION (provided by applicant): Lung cancer is the leading cause of cancer death in women. Although cigarette smoking has been established as the principal risk factor, an estimated 53% of female lung cancer cases worldwide are nonsmokers. The etiology of lung cancer in nonsmokers remains poorly understood. Postmenopausal hormone replacement therapy (HRT) has been shown to increase the risk of developing aggressive lung cancer and lung cancer mortality in two large clinical trials, whereas use of anti-estrogen tamoxifen is associated with a reduced risk of lung cancer death. These findings indicate that estrogens may play an important role in lung carcinogenesis. No study to date, however, has directly evaluated the association between endogenous estrogens and lung cancer risk. On the other hand, soy phytoestrogens, structurally similar to mammalian estrogens, possess anti- estrogenic activities. We recently found in a pilot study that soy food intake was significantly and inversely associated with both lung cancer risk and mortality. We also found that higher urinary levels of two soy isoflavones genistein and glycitein were associated with a lower risk of lung cancer in a small pilot study, and the inversion association was more pronounced for aggressive lung cancer. These findings are in direct contrast to the finding of a significant increase in lung cancer risk and mortality with HRT use in clinical trials. These findings, although preliminary, provide strong support for a novel hypothesis that soy isoflavones, possibly through their anti-estrogenic activities among other mechanisms, may favorably influence the development and progression of lung cancer. We propose in this application to evaluate the potential role of endogenous sex hormones and dietary phytoestrogens in the etiology of lung cancer in female nonsmokers. The proposed study will build upon the Shanghai Women's Health Study (SWHS), a prospective cohort of 74,941 Chinese women. Specifically, we propose to conduct a nested case-control study of 660 incident cases of lung cancer and their individually matched controls in nonsmoking postmenopausal women. Plasma sex hormones and urinary isoflavonoids will be measured in samples collected at baseline using liquid chromatography mass spectrometry based methods. In addition, we will examine the association of soy phytoestrogen intake with lung cancer risk and mortality in the full cohort. The SWHS represents an exceptional opportunity to address such targeted questions given its large size, prospective design, high follow-up rate, and availability of both urine and blood samples. More importantly, it provides repeated dietary assessments and a unique study population with an extremely low prevalence of tobacco product and HRT use but a wide range of soy food intake. Results from the proposed study will fill important gaps in our knowledge regarding the role of endogenous estrogen and dietary phytoestrogen exposure in the etiology of lung cancer and potentially contribute to the development of new strategies against this fatal disease.

 描述（由申请人提供）：肺癌是女性癌症死亡的主要原因。尽管吸烟已被确定为主要危险因素，但估计全球 53% 的女性肺癌病例为非吸烟者。非吸烟者肺癌的病因仍知之甚少。两项大型临床试验表明，绝经后激素替代疗法（HRT）会增加患侵袭性肺癌的风险和肺癌死亡率，而使用抗雌激素他莫昔芬可降低肺癌死亡风险。这些发现表明雌激素可能在肺癌发生中发挥重要作用。然而，迄今为止还没有研究直接评估内源性雌激素与肺癌风险之间的关联。另一方面，大豆植物雌激素在结构上与哺乳动物雌激素相似，具有抗雌激素活性。我们最近在一项试点研究中发现，大豆食物的摄入量与肺癌风险和死亡率呈显着负相关。我们还在一项小型试点研究中发现，尿中两种大豆异黄酮金雀异黄素和黄豆黄素的较高水平与较低的肺癌风险相关，并且这种倒置关联对于侵袭性肺癌更为明显。这些发现与临床试验中使用 HRT 会显着增加肺癌风险和死亡率的发现形成鲜明对比。这些发现虽然是初步的，但提供了强有力的证据 支持一个新的假设，即大豆异黄酮可能通过其抗雌激素活性等机制，可能对肺癌的发生和进展产生有利影响。我们在此申请中建议评估内源性激素和膳食植物雌激素在女性非吸烟者肺癌病因学中的潜在作用。拟议的研究将以上海女性健康研究 (SWHS) 为基础，该研究是一项由 74,941 名中国女性组成的前瞻性队列。具体来说，我们建议对 660 例肺癌发病病例及其在非吸烟绝经后妇女中的单独匹配对照进行巢式病例对照研究。将使用基于液相色谱质谱法的方法测量基线收集的样品中的血浆性激素和尿异黄酮类化合物。此外，我们将在整个队列中研究大豆植物雌激素摄入量与肺癌风险和死亡率的关系。鉴于 SWHS 规模大、前瞻性设计、高随访率以及尿液和血液样本的可用性，它为解决此类有针对性的问题提供了绝佳的机会。更重要的是，它提供了重复的饮食评估和独特的研究人群，其中烟草产品和激素替代疗法的使用率极低，但大豆食品的摄入量很大。拟议研究的结果将填补我们关于内源性雌激素和膳食植物雌激素暴露在肺癌病因学中的作用的重要空白，并可能有助于制定针对这种致命疾病的新策略。