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Genetic ancestry and breast cancer risk in an admixed latin American population from Uruguay
Background: The highest rates of breast cancer have been reported in North America, Oceania and Europe . However, in the temperate region of South America, which includes Argentina , Chile , Uruguay and southern Brazil and which received significant numbers of European migrants, breast cancer prevalence is comparable to that of developed Western countries and is the highest in Latin America . The disparities observed between regions are unclear but may be attributed to differences in environmental and/or genetic exposures. In particular, breast cancer is the most frequent malignancy and the first cause of cancer-related deaths among Uruguayan women. Objective/Hypothesis: The main goal of this project is to determine the genetic contributions from parental populations, namely Europeans, Africans and Native Americans, to Uruguayan breast cancer cases and controls. We hypothesize that a higher risk for disease will be correlated with increased European ancestry. Specific aims: A). to determine ancestral contributions to Uruguayan cases and controls using autosomal and mitochondrial DNA ancestry informative markers; B). to describe the genetic background of the Uruguayan population; C). to examine the relationship between ancestry, disease and disease-related phenotypes; D). to analyze polymorphisms in breast cancer candidate genes and search for association with disease; and E). to evaluate the impact of environmental factors on the distribution of breast cancer throughout the country. Study design: Women affected with breast cancer will be recruited from five public hospitals located across the country to capture as much variation in ancestry and disease prevalence rates as possible. Controls will be identified at the same hospitals from women who have not been diagnosed with breast cancer. About 1000 women will be enrolled altogether. Ancestry proportions, anthropometric measurements and serum levels of endogenous hormones will be obtained for all subjects. The relationship of disease to levels of ancestry as well as to mutations in candidate genes will be explored. Potential outcomes and benefits of the research: This study will contribute towards a better understanding of breast cancer etiology in Uruguay and will be important for future prevention, early identification of cases and treatment.
Breast cancer represents a major health burden in Uruguay where incidence and mortality rates reach those of Western developed countries. Several risk factors, environmental for the most part, have been implicated in the onset of the disease. Genetic predisposition, on the other hand, has not been thoroughly investigated. Towards the end of the 19 th century and beginning of the 20 th century Uruguay received substantial immigration from Europe which had a profound impact on the population make-up and lifestyle. This research project intends to find out whether there is a relationship between ancestry and susceptibility to breast cancer among Uruguayan women. We expect that those women that show a higher European contribution will be at increased risk for the disease. We will recruit affected and unaffected individuals from different parts of the country. We will use validated methodologies to estimate European, West African and Native American ancestral proportions in the population and in each subject. We will also analyze mutations in genes that are likely to contribute to breast cancer to determine if they are present in Uruguayan patients and how important they are in this population. We will perform additional tests in controls to describe the characteristics of the general population and each regional population. Environmental, cultural and sociodemographic factors will be considered as well by means of an extensive questionnaire that will be applied to all participants in the study. This study will be important to better understand the underlying causes of breast cancer, genetic or non-genetic, and will be useful for the optimization of prevention and treatment programs, especially in a small developing country such as Uruguay . In addition, it will have implications regarding neighboring countries, like Argentina , Chile and southern Brazil , that also show elevated breast cancer prevalences.