Admixture Mapping for Breast Cancer in Latinas

描述（由申请人提供）：混合定位是一种在混合祖先群体中鉴定复杂性状基因的新方法。如果易患疾病或不同疾病亚型的等位基因在形成混合种群的祖先种群中具有不同的频率，则混合作图就有效。拉丁裔/西班牙裔人口是一个混合群体，其祖先来自欧洲、美洲原住民和非洲人口。旧金山湾区的拉美裔大多来自墨西哥和中美洲，他们大多是欧洲和美洲原住民的混血儿。我们最近确定了一组标记，用于在该人群中进行混合作图，这些标记为提供全基因组覆盖的欧洲-美洲原住民血统差异提供了信息。我们最近还调查了旧金山湾区拉丁裔人的祖先与乳腺癌风险之间的关系。我们的初步数据表明，在拉丁美洲人中，那些具有较高美洲原住民血统的人患绝经前乳腺癌的风险可能会增加。然而，在绝经后的女性中，欧洲血统较高的女性患乳腺癌的风险更高。在调整了已知的危险因素后，绝经前和绝经后乳腺癌风险与祖先之间的相互作用仍然很显著。基于这些发现，我们假设一些在不同年龄易患乳腺癌的等位基因可以通过混合作图方法来识别。在一项正在进行的乳腺癌病例对照研究中，我们提出了一项混合定位研究，以确定拉丁裔妇女乳腺癌风险的遗传修饰因子。可供分析的总人数将包括1000例拉丁病例和1000例对照病例。

DESCRIPTION (provided by applicant): Admixture mapping is a novel approach to identifying genes for complex traits in populations of mixed ancestry. Admixture mapping works if the alleles which pre-dispose to disease, or to different subtypes of disease, have different frequencies in the ancestral populations which contributed to the admixed population. Latino/Hispanic populations are an admixed group with ancestry from European, Native American and African populations. Latinos in the San Francisco Bay Area are mostly of Mexican and Central American origin who are mostly of mixed European and Native American descent. We have recently identified a set of markers for admixture mapping in this population that are informative for European-Native American ancestry difference that provide whole genome coverage. We have also recently investigated the association between ancestry and breast cancer risk among Latinas in the San Francisco Bay Area. Our preliminary data suggests that among Latinas, those with higher Native American ancestry may be at increased risk of pre-menopausal breast cancer. However, among post-menopausal women, those with higher European ancestry appeared to be at higher risk of breast cancer. The interaction between pre- and post-menopausal breast cancer risk and ancestry remained significant after adjustment for known risk factors. Based on these findings, we hypothesize that some alleles which pre-dispose to breast cancer at different ages may be identifiable by an admixture mapping approach. We propose an admixture mapping study to identify genetic modifiers of breast cancer risk among Latina women in the context of an ongoing case-control study of breast cancer. The total population that will be available for analysis will include 1000 Latina cases and 1000 controls.