Biologically relevant genetic markers of prostate cancer risk and aggressive disease within SA men -Prof Riana Bornman
Prof Riana Bornman
Title of the project
Biologically relevant genetic markers of prostate cancer risk and aggressive disease within South African men.
Background: Prostate cancer (PCa) is not only the most common male cancer worldwide (affecting one in every six men); it is arguably the most heritable of the common cancers (~42-57%). The genetic basis of PCa is however, poorly understood. Clinical management is hindered by lack of reliable biomarkers and the diverse nature of disease course (from asymptomatic to rapid spread and mortality). Besides increased age and a family history of PCa, the only known significant lifetime risk factor for PCa is an African ancestry.
African-American men have a significant higher incidence and mortality of PCa compared with age-matched Europeans and Asians. However, we do not know what the situation in among indigenous African or South African men.
Rationale: Studies focused on defining genetic markers of increased susceptibility and outcomes have been biased towards non-African populations. As at 2012, after six years of genome-wide association studies (GWAS) to identify susceptibility markers of PCa risk, only a single study has focused on African- Americans, while none have been performed on a population within Africa or South Africa. Further limitations include cohort heterogeneity (including both indolent and aggressive PCa patients), biases in genotyping array content towards non-African populations, and lack of biologically significant associations.
Goals and Objectives: The overall objective is firstly to establish a South African prostate cancer cohort and secondly to use this resource to identify biologically relevant markers of PCa that may explain increased risk and aggressive disease associated with an African ancestry, while addressing current limitations in published PCa GWAS association studies (each addressed below).
Following on the findings of McCrow et al. (2016) on the spectrum of mitochondrial genomic variation and associated clinical presentation of prostate cancer in South African men, we performed genome mapping, which revealed a novel subset of large genomic reorganizations in prostate cancer. Complex genomic rearrangements re common molecular events driving prostate carcinogenesis. However, clinical significance has yet to be fully understood. The preliminary findings indicate that these large genomic rearrangements to be early events in prostate cancer that could enhance subtype classification in prostate cancer. This is now being followed up.
We are preparing a manuscript on Prostate Cancer in Africa: A New Look at a Common Disease.