Breast cancer incidence rates vary substantially among different racial and ethnic groups in the U.S. Populations of mixed ethnicity/race may be particularly helpful in understanding the etiologies of such differences. Latinos are a group defined by a common language, but they do not refer to a single race or ethnic group. Instead, Latinos represent many diverse subgroups that are distinct in their demographic characteristics, geographic origin, and genetic ancestry. Latinos have a complex genetic ancestry of Native American, African, and European origin, and individuals within this population are often of mixed ancestry.

Genetic ancestry may be determined in individuals by using genetic markers that are known to have very different frequencies among ancestral populations. For example, a genetic marker that is common among Native Americans but rare among Europeans would suggest higher Native American ancestry in a particular individual. While no single marker can determine ancestry of individuals, a series of highly informative markers may be used to statistically estimate each individual's ancestry. This type of approach has been used in other diseases such as Systemic Lupus Erythematosis and Diabetes Mellitus to understand the relationship between genetic ancestry and disease risk in populations of mixed ancestry. We propose to use the same approach to study the association between genetic ancestry and breast cancer risk among Latinas living in the San Francisco Bay area.

We will use 50 highly informative genetic markers to quantify the ancestry of Latina women with breast cancer (cases) and age-matched Latina women without breast cancer (controls). We plan to compare the genetic measurements of ancestry among the cases and controls. Our main goals are: (1) To determine the percentage of Native American, European, and African ancestry among different Latina subgroups using genetic markers that are informative for ancestry. (2) To compare the ancestry of Latina breast cancer cases and age-matched Latina controls. In addition, we will determine whether any differences in ancestry that we detect between cases and controls are possibly due to differences in hormonal and lifestyle factors that are known to increase or decrease breast cancer risk. (3) To use novel statistical techniques to adjust for any potential differences in ancestry that we may find between cases and controls. We will address this question using DNA samples and interview data from a large case-control study of breast cancer conducted in Latina women living in the San Francisco Bay area. We anticipate approximately 650 cases and 765 controls will be included in this study.

In order to do genetic studies of breast cancer in the genetically complex Latina population, it is imperative that the relationship between genetic ancestry and breast cancer risk is assessed. If there is an association between ancestry and breast cancer risk in this population, then all future studies of breast cancer in the Latina population will need to be adjusted for the differences in ancestry between cases and controls. Our study will not only assess whether there is such a difference, but also explore new ways of statistically adjusting for this difference. Thus, our study will substantially advance the methodology of genetic case-control studies of breast cancer among Latinas. Furthermore, if ancestry from a particular group is associated with increased risk of breast cancer among Latinas, then it may be possible to map genes in this population using a technique called "admixture mapping." Populations such as Latinos, which include several different racial/ethnic subgroups that have recently mixed, display increased linkage disequilibrium -- or association of genetic markers. The increased linkage disequilibrium in this population would decrease the number of genetic markers needed to identify new genetic risk factors for disease. Thus, our study would help to define whether this type of approach -- "admixture mapping" -- may be possible in the Latina population. This may improve methods of genetic association studies in Latinas and ultimately lead to the identification of genetic risk factors for breast cancer in Latinas.