Breast Cancer, Breast Density & Admixture Among Latinas

描述(申请人提供)：乳腺癌发病率在不同种族和民族之间差异很大。两个或两个以上种族混合的混合群体可能会提供对这些差异的原因的洞察。拉美裔美国人主要是欧洲人、美洲原住民和非洲人祖先的混合后裔。在加利福尼亚州，大多数拉丁裔是来自墨西哥和中美洲国家的移民，主要是欧洲人和美洲原住民的后裔。拉丁裔的乳腺癌发病率大大低于高加索人，但高于美洲原住民，这与他们的欧洲人和美国原住民混血的情况是一致的。这个项目将研究拉丁裔的基因血统与乳腺癌风险之间的联系。利用旧金山湾区已建立的拉丁裔病例对照研究，我们将比较240名患有乳腺癌的拉丁裔和300名年龄匹配的拉丁裔对照的遗传血统。将使用一系列对祖先信息高度丰富的遗传标记来估计祖先。分析将针对乳腺癌的已知非遗传风险因素进行调整。我们还将研究乳房X光照相密度与拉丁裔遗传血统之间的联系。乳房X光检查的乳房密度是已知的乳腺癌最强烈的风险因素之一，是一种高度可遗传的特征。为了实现这一目标，我们将招募100名乳房X光密度极高的拉丁裔女性，并将这些女性的基因血统与100名乳房密度极低的拉丁裔女性进行比较。基于这些结果，我们将确定乳腺癌风险和乳房X光照相密度的遗传关联研究是否会受到拉丁裔人群血统的干扰。此外，该项目将测试利用混合人群中增加的连锁不平衡来识别与拉丁裔乳腺癌相关的遗传变异的可行性。

DESCRIPTION (provided by applicant): Breast cancer incidence rates vary widely among different racial and ethnic groups. Admixed populations, in which two or more ethnic groups have mixed, may provide insight into the etiology of these differences. Latino Americans are largely an admixed group descended from European, Native American, and African ancestors. In California, the majority of Latinos are immigrants from Mexico and Central American countries, and are mainly of European and Native American ancestry. Latinas have breast cancer incidence rates that are substantially lower than Caucasians but higher than Native Americans, consistent with their mixed European and Native American descent. This project will examine the association between genetic ancestry among Latinas and breast cancer risk. Using an established case-control study of Latinas in the Bay Area we will compare genetic ancestry among 240 Latinas with breast cancer and 300 age-matched Latina controls. Ancestry will be estimated with a series of genetic markers highly informative for ancestry. Analyses will be adjusted for known non-genetic risk factors for breast cancer. We will also examine the association between mammographic density and genetic ancestry among Latinas. Mammographic breast density is one of the strongest known risk factors for breast cancer and is a highly heritable trait. To address this aim we will recruit 100 Latina women with extremely high mammographic density and compare the genetic ancestry among these women with 100 Latina women with extremely low breast density. Based on these results we will determine whether genetic association studies of breast cancer risk and of mammographic density may be confounded by ancestry in the Latina population. In addition, this project will test the feasibility of using the increased linkage disequilibrium in admixed populations to identify genetic variations associated with breast cancer among Latinas.