Role of Genetic and Lifestyle Interplay in Uterus Cancer

遗传和生活方式相互作用在子宫癌中的作用

• 批准号: 7115303
• 负责人: HERBERT YU
• 金额: $ 58.63万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7115303
• 关键词: apoptosis; behavioral /social science research tag; biological signal transduction; body physical activity; cancer risk; cell proliferation; clinical research; cyclins; diabetes mellitus; female; genetic polymorphism; growth factor receptors; human subject; insulin sensitivity /resistance; insulinlike growth factor; interview; lifestyle; mitogens; nutrition related neoplasm /cancer; nutrition related tag; obesity; polymerase chain reaction; questionnaires; uterus neoplasms; women' s health

DESCRIPTION (provided by applicant): Although estrogens are believed to play a key role in the development of endometrial cancer, evidence indicates that other regulatory molecules are also involved in the disease. High-energy diets, physical inactivity, obesity, insulin resistance, and diabetes are found to be associated with the risk of endometrial cancer, and these associations cannot be explained entirely by the role of estrogens. Mitogenic growth factors are suspected to be involved in these relationships, given their possible link to these lifestyle factors, and their ability to stimulate cell proliferation, to inhibit apoptosis, and to interact synergistically with sex steroid hormones in regulating important cellular activities in sex organs. To date, there have been few epidemiologic studies addressing the role of mitogenic growth factors in endometrial cancer, especially their interplay with lifestyle factors. In this proposal, we hypothesize that certain genetic polymorphisms in the genes encoding mitogenic growth factors and molecules involved in their signal transduction pathway are associated with strong mitogenic activities; these activities synergistically interact with a lifestyle of high-energy diets and low physical activity, resulting in elevated risk for endometrial cancer. To test this hypothesis, we will carry out a population-based case-control study in the state of Connecticut. We will enroll 900 incident cases with primary endometrial cancer, aged 35-79 years, and 900 age-matched control women. Controls will be selected randomly from the state through random-digit dialing. Detailed personal information including menstrual and reproductive history, medical history, estrogen usage, dietary habits, and physical activity will be collected through in-person interview using structured questionnaires. Blood samples (buccal cells when blood is not available) will be collected for DNA analysis. Associations between polymorphisms in the proposed genes and endometrial cancer risk and their interplay with lifestyle factors will be examined using unconditional logistic regression methods. Findings of this study will provide insights into the role of mitogenic growth factors and their interaction with lifestyle factors in the etiology of endometrial cancer.

描述（由申请人提供）：尽管据信雌激素在子宫内膜癌的发展中起关键作用，但证据表明，其他调节分子也参与了该疾病。发现高能饮食，身体不活跃，肥胖，胰岛素抵抗和糖尿病与子宫内膜癌的风险有关，并且这些关联不能完全通过雌激素的作用来解释。鉴于它们可能与这些生活方式因素的联系，以及它们刺激细胞增殖，抑制凋亡的能力，并与性类固醇激素在调节性器官中重要的细胞活性方面协同相互作用，鉴于它们与这些生活方式增殖，刺激细胞增殖，抑制细胞凋亡的能力的可能性，促使有丝分裂生长因子可能与这些关系有关。迄今为止，很少有流行病学研究解决有丝分裂生长因子在子宫内膜癌中的作用，尤其是它们与生活方式因素的相互作用。在此提案中，我们假设在编码促有丝分裂生长因子和信号转导途径中涉及的有丝分裂生长因子和分子的基因中的某些遗传多态性与强促丝分裂活性有关。这些活动协同与高能量饮食和低体育锻炼的生活方式协同互动，导致子宫内膜癌的风险升高。为了检验这一假设，我们将在康涅狄格州进行基于人群的病例对照研究。我们将招募900例原发性子宫内膜癌的事件，年龄35-79岁，并匹配900名年龄匹配的对照妇女。控件将通过随机数字拨号从状态随机选择。详细的个人信息，包括月经和生殖历史，病史，雌激素的使用，饮食习惯和体育锻炼，将通过使用结构化问卷来收集。血液样本（如果没有血液，颊细胞）将收集以进行DNA分析。将使用无条件的逻辑回归方法检查拟议基因中的多态性与子宫内膜癌风险之间的关联及其与生活方式因素的相互作用。这项研究的结果将提供有关有丝分裂生长因子的作用及其与生活方式因子在子宫内膜癌病因中的相互作用的见解。