Association of genetic variants with prostate cancer in Africa: a concise review

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.

Role of single nucleotide polymorphisms of the HSD3B1 gene (rs6203 and rs33937873) in the prediction of prostate cancer risk

“…In the US, those with a family history of PC should be advised of their significantly increased PC risk to ~9–10% in their lifetime ( 69 ). In Africa, some studies found a correlation between PC incidence in different African cultures and their family history reached between 30–70% ( 69 , 70 ). With respect to this biological heterogeneity of PC, the observation is important in understanding PC etiology and incidence risk factor to correctly assess the clinical state of the patient using PSA continuous screening to avoid aggressiveness and high mortality rate.…”

Review of prostate cancer genomic studies in Africa

“…Likewise, in 2015, a study among a cohort of patients in Senegal showed that hereditary factors or ancestral factors (black or African) did not affect the increase in the risk of PCa ( Acheampong et al, 2021 ). However, this result seems to be applicable to other African populations ( Acheampong et al, 2021 ).…”

“…Likewise, in 2015, a study among a cohort of patients in Senegal showed that hereditary factors or ancestral factors (black or African) did not affect the increase in the risk of PCa ( Acheampong et al, 2021 ). However, this result seems to be applicable to other African populations ( Acheampong et al, 2021 ). Recently, Conti et al (2021) conducted a multiancestry meta-analysis of PCa GWAS studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with PCa risk in men from mixed populations including men from African Americans.…”

“…However, there is still lack of studies conducted on African populations. The outcome of GWAS presents a step forward in better understanding the evidence of the heterogeneity of African populations ( Schlebusch et al, 2017 ; Acheampong et al, 2021 ) and proves the need for further studies of the genomics of PCa and their contributions to racial disparities of this disease.…”

“…Therefore, further functional and genetic epidemiological research is needed on all continents, particularly in Africa, to gain a more in-depth understanding of the different genome variations and variants involved in the pathophysiology of PCa and thus to move toward targeted treatment programs suited to Africans. To make this a reality, large-scale genomic consortia must be set up to investigate the omics of African populations ( El Jaddaoui et al, 2020 ; Acheampong et al, 2021 ). Of note, the global profiling of the genetic architecture of PCa cannot be straightforward without the analysis of the African genome.…”