THE 4 CORNERS BREAST AND ENDOMETRIAL CANCER STUDY

乳腺癌和子宫内膜癌的 4 个角落研究

• 批准号: 6173921
• 负责人: KATHY B BAUMGARTNER
• 金额: $ 84.07万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6173921
• 关键词: Hispanic Americans; Native Americans; androgen receptor; body weight; breast neoplasms; cancer risk; caucasian American; clinical research; female; gene environment interaction; genetic markers; genetic polymorphism; genetic susceptibility; human genetic material tag; human subject; insulin; insulin receptor; insulin sensitivity /resistance; neoplasm /cancer epidemiology; neoplasm /cancer genetics; obesity; racial /ethnic difference; uterus neoplasms; vitamin D receptors; women's health

DESCRIPTION: (Adapted from Applicant's Abstract) The incidence of breast and endometrial cancers varies almost three-fold between non-Hispanic white populations and Native American and Hispanic populations living in the 4-Corners area of the United States (Arizona, New Mexico, Colorado, and Utah). Interestingly, although American Indian and Hispanic women have higher prevalences of many risk factors for breast and endometrial cancer identified in non-Hispanic white women (e.g., obesity, low levels of vigorous physical activity, low intakes of fruits and vegetables, high rates of insulin resistance) they have lower cancer incidence rates. In this study the investigators focus on the metabolic factors of obesity/weight changes and indicators of insulin status as they relate to breast and endometrial cancers. Obesity is associated both with estrogen and insulin by two interrelated disease pathways. Insulin may influence cancer risk directly through its effects on insulin-like growth factor (IGF) and its binding proteins (IGFBPs) and well as indirectly through its effect on estrogen levels. The investigators propose focusing on the insulin pathway because of the high levels of insulin pathway dysfunction in this population. A multi-center case-control study is proposed that targets women living in the 4-Corners area; the study will consist of a 2.5 hour in-person interview and a blood draw. Over a three-year case ascertainment period, the study will enroll 3000 breast cancer cases, 450 endometrial cancer cases and 3000 controls, half of whom will be Hispanic/Native American and half of whom will be non-Hispanic white women between the ages of 25 and 79. Molecular variants of genes that influence obesity and insulin (androgen receptor gene (AR), vitamin D receptor gene(VDR), insulin receptor (ADRB3)) will be examined both independently and in conjunction with metabolic factors to determine differences in genetic susceptibility in the population. Because of the diverse population (Hispanics, Native American, and non-Hispanic white women), the investigators propose to evaluate ethnic background and genetic admixture in relationship to gene markers, environmental factors, and breast and endometrial cancer risk. Genetic admixture (Ameridian to European genetic mixture) is a novel and innovative way to study the continuum of ethnic diversity. C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women.

描述：（改编自申请人的摘要）乳腺癌和乳腺癌的发病率 非西班牙裔白人之间的子宫内膜癌差异几乎三倍 人口以及居住在该地区的美洲原住民和西班牙裔人口 美国 4 角区（亚利桑那州、新墨西哥州、科罗拉多州和犹他州）。 有趣的是，尽管美洲印第安人和西班牙裔女性的生育率更高 确定了许多乳腺癌和子宫内膜癌危险因素的患病率 非西班牙裔白人女性（例如肥胖、体力活动水平低） 活动量大、水果和蔬菜摄入量低、胰岛素水平高 抵抗力）他们的癌症发病率较低。在这项研究中 研究人员重点关注肥胖/体重变化的代谢因素和 与乳腺癌和子宫内膜癌相关的胰岛素状态指标。 肥胖通过两个相互关联的因素与雌激素和胰岛素有关 疾病途径。胰岛素可能通过其直接影响癌症风险 对胰岛素样生长因子 (IGF) 及其结合蛋白 (IGFBP) 的影响 以及通过其对雌激素水平的间接影响。调查人员 由于胰岛素水平高，建议重点关注胰岛素途径 该人群中的通路功能障碍。多中心病例对照研究是 提议针对居住在 4-Corner 地区的妇女；该研究将 包括 2.5 小时的面对面访谈和抽血。三年多来 病例确定期间，该研究将招募3000例乳腺癌病例，其中450例 子宫内膜癌病例和 3000 名对照者，其中一半将 西班牙裔/美洲原住民，其中一半是非西班牙裔白人女性 年龄在 25 岁至 79 岁之间。影响基因的分子变异 肥胖与胰岛素（雄激素受体基因（AR）、维生素D受体基因（VDR）、 胰岛素受体（ADRB3））将被独立地和在 结合代谢因素来确定遗传差异 人群的易感性。由于人口多样化（西班牙裔、 美洲原住民和非西班牙裔白人女性），调查人员建议 评估种族背景和遗传混合与基因的关系 标记物、环境因素以及乳腺癌和子宫内膜癌风险。遗传 混合物（美洲到欧洲的基因混合物）是一种新颖且创新的方式 研究种族多样性的连续性。 C肽、糖化血红蛋白、 IGF-1 和 IGFBP3 将针对乳房和子宫内膜进行评估 一部分女性患有癌症。