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）：虽然雌激素被认为在子宫内膜癌的发展中发挥着关键作用，但有证据表明其他调节分子也参与该疾病。研究发现，高能量饮食、缺乏身体活动、肥胖、胰岛素抵抗和糖尿病与子宫内膜癌的风险相关，但这些关联不能完全用雌激素的作用来解释。有丝分裂生长因子被怀疑与这些关系有关，因为它们可能与这些生活方式因素有关，并且它们具有刺激细胞增殖、抑制细胞凋亡以及与性类固醇激素协同相互作用调节性器官重要细胞活动的能力。迄今为止，很少有流行病学研究探讨促有丝分裂生长因子在子宫内膜癌中的作用，特别是它们与生活方式因素的相互作用。在这个提议中，我们假设编码促有丝分裂生长因子和参与其信号转导途径的分子的基因中的某些遗传多态性与强有丝分裂活性相关。这些活动与高能量饮食和低体力活动的生活方式协同相互作用，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开展一项基于人群的病例对照研究。我们将招募 900 名年龄 35-79 岁的原发性子宫内膜癌病例和 900 名年龄匹配的对照女性。控件将通过随机数字拨号从状态中随机选择。将使用结构化问卷通过面对面访谈收集详细的个人信息，包括月经和生育史、病史、雌激素使用情况、饮食习惯和身体活动。将收集血液样本（没有血液时采集口腔细胞）进行 DNA 分析。将使用无条件逻辑回归方法检查所提出的基因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。这项研究的结果将深入了解促有丝分裂生长因子的作用及其与生活方式因素在子宫内膜癌病因学中的相互作用。