Disparities in Breast Cancer: Development and Survival in Hispanic and NHW Women

描述（由申请人提供）：西班牙裔和非西班牙裔白人（NHW）女性的乳腺癌发病率差异超过两倍；西班牙裔妇女在诊断后的生存率比非西班牙裔妇女差。我们建议利用来自四个角落州、加利福尼亚州和墨西哥城的现有资源，评估美洲印第安人与非裔美国妇女在乳腺癌发展和生存方面的健康差异。使用的现有资源将是行为和社会生活方式暴露数据以及在访谈时获得的DNA。生存数据一直在进行中，并将继续通过当地SEER和CDC肿瘤登记处进行监测。遗传和生活方式数据来自大约8039例西班牙裔和非西班牙裔乳腺癌病例和基于人群的对照。通过汇集三项研究的资源，我们将有效地研究我们认为对乳腺癌发展和生存很重要的生物学途径，并影响西班牙裔和非西班牙裔妇女乳腺癌发病率的差异。对遗传因素的评估将集中在与胰岛素、雌激素和炎症相关途径共同作用的途径上，并代表一个趋同点。该通路被我们称为激素、炎症和能量功能趋同（CHIEF）信号通路，尚未在西班牙裔或非西班牙裔白人女性中进行全面研究，将包括使用Illumina平台研究的基因包括SOC1、SOC2、AKT、FRAP1（又名mTOR）、P13K、STK11、AMP、PTEN、VEGF、S6K1、S6K2、CRP、NFKB、IKB、IL10、IL8、IL6、TNFalpha。乳腺癌的相关性将在西班牙裔和非西班牙裔美国妇女的基因多态性和单倍型之间进行测试，并按美洲印第安血统的比例进行测试。信号通路基因之间的相互作用以及与非甾体抗炎药、阿司匹林、BMI、雌激素和身体活动的相互作用将被检查。这些遗传因素将与生存率进行评估，以确定其对西班牙裔和非西班牙裔妇女生存差异的贡献。公共卫生相关性：本研究将促进我们对西班牙裔和美洲印第安妇女以及全体妇女乳腺癌病因学的了解。高风险人群和低风险人群之间的对比将以具有成本效益的方式加强这一努力。结果可以确定药物治疗的潜在靶点。

DESCRIPTION (provided by applicant): The incidence rates of breast cancer vary more than two-fold between Hispanic and non-Hispanic white (NHW) women; Hispanic women have worse survival after diagnosis than NHW women. We propose to evaluate these health disparities in breast cancer development and survival along the continuation of American Indian to NHW women utilizing existing resources from the 4 Corner's States, California, and Mexico City. Existing resources utilized will be behavioral and social lifestyle exposure data along with DNA obtained at the time of interview. Survival data has been ongoing and will continue to be monitored via local SEER and CDC tumor registries. Genetic and lifestyle data are available from approximately 8039 Hispanic and NHW cases of breast cancer and population-based controls. By pooling resources from three studies, we will efficiently examine a biological pathway that we believe is important to breast cancer development and survival and that influences differences in breast cancer rates among Hispanic and NHW women. Evaluation of genetic factors will focus on a pathway that appears to work in conjunction with insulin-, estrogen-, and inflammation-related pathways and represents a point of convergence. This pathway, which we call the Convergence of Hormones, Inflammation, and Energy Functioning (CHIEF) Signaling Pathway has not been studied comprehensively in either Hispanic or non-Hispanic white women and will include genes to be studied include SOC1, SOC2, AKT, FRAP1(alias mTOR), P13K, STK11, AMP, PTEN, VEGF, & S6K1,S6K2, CRP, NFKB, IKB, IL10, IL8, IL6, TNFalpha using an Illumina platform. Breast cancer associations will be tested between genetic polymorphisms and haplotypes of these genes in Hispanic and NHW women and by proportion of American Indian ancestry. Interaction of signaling pathway genes with each other and with NSAIDs, aspirin, BMI, estrogen, and physical activity will be examined. These genetic factors will be evaluated with survival to determine their contribution to survival differences observed for Hispanic and NHW women. PUBLIC HEALTH RELEVANCE: This study will advance our understanding of breast cancer etiology in Hispanic and American Indian women as well as women overall. The contrast between high and low risk populations will enhance this effort in a cost-efficient manner. Results could identify potential targets for drug therapy.