Genetic studies of cancer in populations of African ancestry and Latinos

Genome-wide association studies (GWAS) in the past decade have been successful in identifying thousands of common genetic susceptibility loci for cancers. However, non-European populations were underrepresented in GWAS samples to date. The clinical value of genetic information in guiding personalized medicine in populations of non-European ancestry will require additional discovery and risk locus characterization efforts across populations. In this dissertation, I aim to expand the current knowledge of genetic susceptibility for multiple cancers to the underrepresented populations of Africa and Latino ancestry. In chapter 2, I conducted the first genetic risk characterization and GWAS study of prostate cancer (PrCa) in men from Eastern Africa among cases and controls from Uganda. In chapter 3, I assembled all existing genetic studies of PrCa in Latino men to search for novel risk alleles as well as to determine whether known PrCa risk alleles are important in capturing PrCa risk in Latino men. I also explored whether genetic background/ancestry modified associations with single variants and a PrCa polygenic risk score in Latino men. In chapter 4, I combined all existing multiple myeloma GWAS data for men and women of African ancestry. In addition to scanning for novel risk regions and assessing the aggregated effect of known risk loci on multiple myeloma risk, I also comprehensively examined each known risk region to find markers that better capture multiple myeloma genetic risk in this high-risk population. These studies show that genetic analyses of these cancers in non-European ancestry populations are imperative in developing ethnic-specific polygenic scores that are informative to improve prevention, screening and treatment of cancers in these diverse populations.