BIOMEDICAL (BASIC)

生物医学（基础）

• 批准号: 7938481
• 负责人: Marc James Gunter
• 金额: $ 32.91万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-15 至 2011-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7938481
• 关键词: BIOMEDICAL; BASIC

The Women's Health Initiative Clinical Trials (WHI-CT) found that hormonal therapy With combined estrogen and progestin (E+P), but not estrogen alone (E), significantly reduced the risk of colorectal cancer in postmenopausal women, However, the biologic mechanisms underlying the protective effect of E+P, and explaining its absence in E, are unknown. Indeed, little at all is known regarding the role of sex hormones in colore~t¿l tumorigenesis. We recently observed a significant positive association between endogenous estradiol levels and colorectal cancer among women enrolled in the WHI Observational Study. This finding, though consistent with in vitro data that demonstrate mitogenic effects of estradiol in the colon, requires validation in other study populations. Furthermore, no studies to our knowledge have assessed the relation of colorectal cancer with progesterone, the factor that most obviously distinguishes E+P from E. The primary objective of the proposed investigation is, therefore, to evaluate the association of incident colorectal cancer with estradiol, estrone, progesterone and sex hormone binding globulin among women enrolled in the untreated arms of the WHI-CT (women not using E or E+P). Using established methods, we will measure these hormonal factors in 400 incident colorectal cancer cases and 800 matched controls. Determining the role of sex hormones in the development of colorectal cancer is essential to understanding the protective effects of E+P and, from a scientific perspective, wil provide insight into previously uncharacterized carcinogenic pathways.

妇女健康倡议临床试验（WHI-CT）发现，激素治疗联合雌激素和孕激素（E+P），但不是单独雌激素（E），显着降低风险 然而，E+P保护作用的生物学机制以及解释其在E中的缺失尚不清楚。其实，很少有。 关于性激素在恶性肿瘤发生中的作用。我们最近观察到内源性雌二醇水平与结直肠癌之间存在显著的正相关 在参加WHI观察性研究的女性中。这一发现，虽然与体外数据一致，证明了雌二醇在结肠中的促有丝分裂作用，但需要在其他研究中验证。 研究人群。此外，据我们所知，没有研究评估结直肠癌与孕酮的关系，孕酮是最明显区分E+P和E的因素。 因此，本研究的主要目的是评估大肠癌与雌二醇、雌酮、孕酮和性激素结合球蛋白的关系 入组WHI-CT未治疗组的女性（未使用E或E+P的女性）。使用已建立的方法，我们将测量400例结肠直肠癌患者的这些激素因素 病例组和800例对照组。确定性激素在结直肠癌发展中的作用对于理解E+P的保护作用至关重要， 的观点，将提供深入了解以前未知的致癌途径。