Edith Cowan University, Research Online, Perth, Western Australia
Abstract
Background: Prostate cancer (PCa) has one of the highest heritability of all major cancers, where the genetic contribution has been documented, and knowledge about the molecular genetics of the disease is increasing. However, the extent and aspects to which genetic variants explain PCa heritability in Africa are limited. Main body: In this review, we summarize studies that highlight how identified genetic variants explain differences in PCa incidence and presentation across ethnic groups. We also present the knowledge gaps in PCa genetics in Africa and why Africa represents an untapped potential ground for genetic studies on PCa. A significant number of genome-wide association studies, linkage, and fine-mapping analyses have been conducted globally, and that explains 30–33% of PCa heritability. The African ancestry has a significant mention in PCa incidence and presentation. To date, the candidate gene approach has replicated 23 polymorphisms including dinucleotide and trinucleotide repeats in 16 genes. CYP17-rs743572, CYP3A4-rs2740574, CYP3A5-rs776746, CYP3A43-rs501275, and haplotype blocks, containing these variants, are significantly associated with PCa among some population groups but not others. With the few existing studies, the extent of genetic diversity in Africa suggests that genetic associations of PCa to African ancestry go beyond nucleotide sequence polymorphisms, to a level of environmental adaptation, which may interpret genetic risk profiles. Also, the shreds of evidence suggest that evolutionary history contributes to the high rates of PCa relative to African ancestry, and genetic associations do not always replicate across populations. Conclusion: The genetic architecture of PCa in Africa provides important contributions to the global understanding of PCa specifically the African-ancestry hypothesis. There is a need for more prostate cancer consortiums to justify the heritable certainties of PCa among Africans, and emphasis should be placed on the genetic epidemiological model of PCa in Africa
