Defining the evolutionary roles of the cancer disparity CRYβB2P1 pseudogene
Fall 2020 Graduate Student Award in Cancer and Evolution
The field of ‘health disparities’ is concerned with studying the differential effects of diseases on people due to their race, age, or sex among other socioeconomic factors. For example, the burden of breast cancer is disproportionately distributed among women of different races, with African Americans having worse survival compared to their Caucasian American counterparts. Breast cancer has different subtypes with varying degrees of aggressiveness and African American patients were shown to have higher proportions of the more aggressive breast cancer subtypes compared to other races. This disparity, and others, can be explained in the context of evolution which has shaped the genetic landscapes of different races in order to adapt environments. However, such genetic adaptations can have detrimental effects on health when the living environment changes. In line with these facts, our research shows one particular gene called P1 to be a potential driver of the breast cancer disparity observed in African American women. Our studies on this gene show that its expression is substantially higher in African American healthy tissues and African American tumors compared to other races. We have also shown that this gene controls various aspects of tumor progression such as proliferation, tumor volume, and spread to other organs. In this proposal, we aim to investigate the role of evolution in shaping the P1 gene over the ages and whether P1 genetic code has diverged in different populations to have differential effects on health and disease. We will rely on publicly available genomic databases to compare the genetic codes of P1 in different races. Next, we will verify in the lab the biological effects these different P1 variants could have to drive breast cancer tumor aggressiveness. This proposed study will help further our understanding of the role of genetic evolution in breast cancer disparity.