Racial disparities in breast cancer risk and gene expression-roles of genetics and lifestyle factors - PROJECT SUMMARY African American (AA) women have 40% higher breast cancer mortality and are more likely to be diagnosed with aggressive subtypes, such as triple negative breast cancer, than European American (EA) women. Exact reasons for these disparities remain unclear – but genetics and lifestyle may both play a role. However, it is unclear how genetic and lifestyle factors contribute to racial differences in molecular profiles of breast cancer. Our recent collaboration with Zambian cancer researchers presents a unique opportunity to include African Zambian (AZ) breast cancer patients in research to help reveal the underlying mechanisms for breast cancer racial disparity. Given the drastic differences in lifestyle and environmental exposures, yet relatively small genetic differences between AA and AZ, including AZ, AA, and EA breast cancer patients in one study will offer an excellent opportunity to disentangle the contribution of genetic predispositions from lifestyle exposures on the molecular profiles and tumor characteristics of breast cancer. We propose to recruit 250 incident AZ breast cancer patients, collect clinical and lifestyle data, obtain tumor tissues, and performing RNA sequencing (RNA-Seq). These data will be compared with existing data from the Southern Community Cohort Study. Specially, our study has the following aims: 1) to recruit 250 African Zambian women with pathologically confirmed breast cancer at the Cancer Disease Hospital in Lusaka, Zambia; 2) to derive molecular profiles of breast cancer in AZ women and compare with those from AA and EA women. We will perform RNA-Seq on breast tumor tissue samples from AZ patients to derive gene expression levels, molecular intrinsic subtypes of breast cancer, and PAM50-based risk of recurrence scores (ROR-S). The demographic, clinical, and molecular data will be summarized and compared across these three racial/ethnic groups. Expression levels of known breast cancer susceptibility genes, molecular intrinsic subtypes, and ROR-S derived in Aim 2 will be utilized to distinguish the differential effects of genetic ancestry versus lifestyle on breast cancer molecular phenotype among the three racial/ethnic groups. This will be the first epidemiological study to compare molecular profiles of breast cancer across AZ, AA, and EA women, shedding light on the underlying genetic and lifestyle factors that contribute to racial disparities in molecular profiles of breast cancer. This study will generate important preliminary data informing a full-scale investigation to delineate variances in genetic predispositions and lifestyle factors in association with breast cancer risk. This will also be the first molecular epidemiology study of breast cancer in Zambia, laying the foundation for conducting etiological research on breast cancer in the country.
