Nearly 15% of American women will be diagnosed with breast cancer in their lifetimes. But the underlying genetic basis for breast cancer risk remains incomplete. What is known is that many women at risk for breast cancer share common changes in their DNA sequence, and that these changes are highly enriched for DNA elements called enhancers. Since enhancers play key roles in regulating the expression of genes, we hypothesize that genetic variation leads to increased breast cancer risk by altering the activity of enhancers, with consequent changes in the expression of cancer-promoting genes. The central obstacle we face today is that the identities of these cancer-promoting enhancers and their...

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Nearly 15% of American women will be diagnosed with breast cancer in their lifetimes. But the underlying genetic basis for breast cancer risk remains incomplete. What is known is that many women at risk for breast cancer share common changes in their DNA sequence, and that these changes are highly enriched for DNA elements called enhancers. Since enhancers play key roles in regulating the expression of genes, we hypothesize that genetic variation leads to increased breast cancer risk by altering the activity of enhancers, with consequent changes in the expression of cancer-promoting genes. The central obstacle we face today is that the identities of these cancer-promoting enhancers and their target genes remains undefined. By applying a newly developed high-throughput technology to a diverse panel of breast cancer cells, the goal of this project is to examine the top breast cancer risk loci to identify the enhancers, genes, and pathways contributing to breast cancer risk. Successful completion of this research will enable the targeting of these genes prognostically for early breast cancer detection. Thus, this research stands to benefit most the women who are at risk of developing breast cancer, but for whom we currently lack the means for early molecular detection. Such early-stage detection of breast cancer, when it is clinically operable before metastasis, will significantly reduce the burden of this disease. Therefore, this research directly addresses CPRIT’s mission of ending breast cancer. In summary, our proposed work to reveal the genetic factors leading to breast cancer risk will be a key step towards transformational improvements in the prognostication and early detection of breast cancer.

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