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

描述(申请人提供)：西班牙裔和非西班牙裔白人(Nhw)女性之间的乳腺癌发病率相差两倍以上；拉美裔女性在确诊后的存活率比nhw女性差。我们建议利用四个角落的州、加利福尼亚州和墨西哥城的现有资源，评估美国印第安人到NHW妇女在乳腺癌发展和存活率方面的健康差异。使用的现有资源将是行为和社会生活方式暴露数据以及采访时获得的DNA。生存数据一直在进行中，并将继续通过当地的SEER和CDC肿瘤登记进行监测。遗传和生活方式数据来自大约8039例西班牙裔和NHW乳腺癌和基于人群的对照病例。通过汇集三项研究的资源，我们将有效地检查一条生物学途径，我们认为这条生物学途径对乳腺癌的发展和生存非常重要，并影响西班牙裔和NHW妇女乳腺癌发病率的差异。对遗传因素的评估将集中在一条似乎与胰岛素、雌激素和炎症相关的途径一起发挥作用的途径上，并代表一个汇合点。这一途径，我们称之为激素、炎症和能量功能(首席)信号通路，尚未在西班牙裔和非西班牙裔白人女性中得到全面研究，将包括使用Illumina平台进行研究的基因，包括SOC1、SOC2、AKT、FRAP1(别名mTOR)、P13K、STK11、AMP、PTEN、VEGF、&S6K1、S6K2、CRP、NFKB、IKB、IL10、IL8、IL6、TNFAlpha。这些基因的遗传多态和单倍型在西班牙裔和nhw女性中以及美国印第安人血统的比例之间的相关性将被测试。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、体重指数、雌激素和体力活动的相互作用将被检测。这些遗传因素将与存活率一起评估，以确定它们对观察到的西班牙裔和NHW妇女存活率差异的贡献。公共卫生相关性：这项研究将促进我们对拉美裔和美国印第安人女性以及整个女性乳腺癌病因的理解。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.