Prostate cancer and genetics in men of African descent, 2020

Atlanta University and Clark Atlanta University Theses and Dissertations
Prostate cancer and genetics in men of African descent, 2020
Harlemon, Maxine
Contributor to Resource:
Bowen, Nathan J.
Date of Original:
Degrees, Academic
Dissertations, Academic
United States, Georgia, Fulton County, Atlanta, 33.749, -84.38798
Men of African descent have at least a two-fold increased incidence and mortality rate of prostate cancer. The heritability rate for prostate cancer is ~58%. Genome-wide association studies (GWAS) have identified over 100 susceptibility loci associated with prostate cancer. These variants have potential to address genetic factors that may predispose one to prostate cancer. Unfortunately, GWAS have revealed significant underrepresentation in non-European populations and the arrays used for genotyping are ill-equipped to identify associations that are specific to men of African descent. The MADCaP Network Array working group developed a genotyping array that is optimized for studies of African populations. The MADCaP Array contains over 1.5 million markers that includes a high density of positions in regions of the genome associated with prostate cancer. We tested the MADCaP Array by genotyping over 800 prostate cancer cases and controls from seven urban study sites in sub-Saharan Africa. We find that genes mirror geography. We identify highly differentiated loci in Africa and include allele frequencies at cancer associated loci as an additional novel resource. Although genetic risks of prostate cancer are heterogeneous across African populations, polygenic risk scores are lower in Senegal than in Nigeria. We also explored the effects of admixture on elevated risks of prostate cancer in African-American men. Mapping by Admixture Disequilibrium is based on the concept that admixture occurs when recombination events result in regions of the genome that have alleles that are in linkage disequilibrium and are ancestrally linked to the parental population. We have utilized genotype data from ~1300 cases and ~1300 controls for prostate cancer of African-American men to fine map ancestry across the genome. We used this information to form rank enrichment of African ancestry in cases vs. controls within ~25000 genes and in 200kb window size across the genome. The ranked list showed African enrichment in chromosomes 2 and X. We intersected the ranked list with curated gene sets to determine possible functional regions that may be associated with the increased risk for prostate cancer according to ancestry within the gene.
Date of award: 2020-05
Degree type: dissertation
Degree name: Doctor of Philosophy (PhD)
Granting institution: Clark Atlanta University
Department: Department of Biological Sciences
Advisor: Bowen, Nathan J.
Metadata URL:
Holding Institution:
Clark Atlanta University