Abstract
BackgroundAlthough African ancestry represents a significant risk factor for prostate cancer, few studies have investigated the significance of prostate cancer and relevance of previously defined genetic and epidemiological prostate cancer risk factors within Africa. We recently established the Southern African Prostate Cancer Study (SAPCS), a resource for epidemiological and genetic analysis of prostate cancer risk and outcomes in Black men from South Africa. Biased towards highly aggressive prostate cancer disease, this is the first reported data analysis.MethodsThe SAPCS is an ongoing population-based study of Black men with or without prostate cancer. Pilot analysis was performed for the first 837 participants, 522 cases and 315 controls. We investigate 46 pre-defined prostate cancer risk alleles and up to 24 epidemiological measures including demographic, lifestyle and environmental factors, for power to predict disease status and to drive on-going SAPCS recruitment, sampling procedures and research direction.ResultsPreliminary results suggest that no previously defined risk alleles significantly predict prostate cancer occurrence within the SAPCS. Furthermore, genetic risk profiles did not enhance the predictive power of prostate specific antigen (PSA) testing. Our study supports several lifestyle/environmental factors contributing to prostate cancer risk including a family history of cancer, diabetes, current sexual activity and erectile dysfunction, balding pattern, frequent aspirin usage and high PSA levels.ConclusionsDespite a clear increased prostate cancer risk associated with an African ancestry, experimental data is lacking within Africa. This pilot study is therefore a significant contribution to the field. While genetic risk factors (largely European-defined) show no evidence for disease prediction in the SAPCS, several epidemiological factors were associated with prostate cancer status. We call for improved study power by building on the SAPCS resource, further validation of associated factors in independent African-based resources, and genome-wide approaches to define African-specific risk alleles.
Highlights
African ancestry represents a significant risk factor for prostate cancer, few studies have investigated the significance of prostate cancer and relevance of previously defined genetic and epidemiological prostate cancer risk factors within Africa
Stage 1: Genotype analysis We recently described the Southern Bantu population groups included in this study as forming a single genetic cluster distinct from other African populations including both Eastern and Western Bantu-derived populations, supporting the combined analysis of Southern Bantu men for genetic association studies [Tindall et al, submitted]
Of note is that the T allele of rs10090154 showed a protective effect in our study (OR = 0.55, 95% confidence intervals (CI) 0.36-0.83), in contrast to previous reports including the discovery Europeanbased genome-wide association studies (GWAS), which suggests the T allele is associated with increased prostate cancer risk (OR = 1.67) [28]
Summary
African ancestry represents a significant risk factor for prostate cancer, few studies have investigated the significance of prostate cancer and relevance of previously defined genetic and epidemiological prostate cancer risk factors within Africa. We recently established the Southern African Prostate Cancer Study (SAPCS), a resource for epidemiological and genetic analysis of prostate cancer risk and outcomes in Black men from South Africa. The heterogeneous nature of prostate cancer and the potential of indirect influences affecting PSA levels, has prompted investigations into alternate prognostic marker development, the early detection of aggressive disease. Alternative markers such as prostate cancer antigen 3 (PCA3) [5] and several genetic risk profiles [6,7] have been proposed to compliment PSA screening methods, but these methods are still being fine-tuned for clinical application
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