Testing for BRCA1/2 and ataxiatelangiectasia mutated in men with high prostate indices: An approach to reducing prostate cancer mortality in Asia and Africa

摘要

A recently published review article titled “Current progress and questions in germline genetic of prostate cancer” enumerated some pertinent questions which impact on prostate cancer (PCa) surveillance and management [1]. Literature across the world reveals that the age- standardized incidence rate per 100 000 of PCa is lower in Asia (11.5) and Africa (26.6) when compared with Latin America/Caribbean (56.4), Europe (62.1) and Oceania (79.1); surprisingly the mortality rate per new case is higher in Africa (52.2%) and Asia (39.8%) when compared with Europe (23.9%), Oceania (19.1%), and Latin America/Carib- bean (16.8%) [2]. Globally, screening for prostate-specific antigen (PSA) is an approach aimed at identifying PCa at its early stages. However, early identification of individuals at risk of developing aggressive/lethal PCa remains a chal- lenge among clinicians. A follow-up study carried out in the United Kingdom (UK) and Ireland showed that 4.3% and 5.8% of those carrying BRCA1 and BRCA2 mutations developed PCa with a standardized incidence ratio (SIR) of 2.4 and 4.5, respectively [3]. However, the study was not explicit on whether the patients developed lethal or indolent PCa. Another study carried out in the UK revealed that after 3 years of active histological follow-up, 5.2%, 3.4%, 3.0%, and 2.7% of BRCA2 carriers, BRCA1 carriers, BRCA2 non-carriers, and BRCA1 non-carriers developed aggressive PCa, respec- tively [4]. Nyberg et al. [3] observed that those with a pos- itive family history have SIR of 3.2 and 7.3 for BRCA1 and BRCA2 while those with a negative family history have SIR of 2.3 and 3.9 for BRCA1 and BRCA2, respectively. In the United State (US), a 26 years follow-up exercise revealed that 13.0% of actively monitored men developed PCa, out of which 13.9% developed aggressive PCa [5]. Evidence showed that the frequency of pathogenic mutations was higher in pa- tients with aggressive PCa (6.1%) than in patients with localized PCa (1.4%) [6]. The frequency of BRCA1, BRCA2, and ataxiatelangiectasia mutated (ATM) were higher in aggressive PCa (0.6%, 3.5%, and 1.9%) than in localized PCa (0.4%, 0.8%, and 0.4%, respectively). This suggests that apart from BRCA2 mutation, BRCA1 mutation and ATM play critical roles in the development of aggressive carcinogenesis. However, the extent to which the germline mutations drive carcinogenesis differs with race and across continents. Na et al. [6] showed that carrier rates of pathogenic mutations of BRCA1/2, ATM, and DNA repair genes (DRGs) are higher in Chinese (0.0%/13.6%, 4.6%, and 18.2%) than in Caucasians (0.8%/3.1%, 1.5%, and 5.4%) and African American (0.0%/ 0.0%, 3.3%, and 3.3%, respectively). Chandrasekar et al. [7] observed that the prevalences of hereditary breast and ovarian cancer (HBOC), hereditary cancer syndrome (HCS), and hereditary prostate cancer (HPC) were higher in African American than in Caucasians while the prevalences of Lynch syndrome (LS) was higher in African American than in Cau- casians, with differences of 7.2%, 4.2%, 1.2% and 3.5%, respectively. They observed that the prevalence of HCS, HBOC, and LS connected to family history were higher in African American than in Caucasians with a difference of 12.6%, 15.6%, and 15.6%, respectively. From their study, the prevalences of BRCA1 and BRCA2 were higher in African American (14.3% and 3.6%, respectively) than in Caucasians (5.0% and 3.5%, respectively) while the prevalence of ATM was higher in Caucasians (0.7%) than in African American (0.0%).