Age- and gender-based frequency and association of common myeloproliferative mutations in a South African cohort

Background: Age, gender, and mutation type are key risk factors for myeloproliferative neoplasms (MPNs). Africa remains under-represented in global cancer statistics due to limited population-based genomic data. Objective: To determine the frequency and demographic associations of common MPN-related genetic abnormalities in the South African population. Methods: A retrospective cross-sectional analysis of cytogenetic results for Janus kinase-2 p.V617F (JAK-2 p.V617F), Janus kinase-2 exon 12 (JAK-2 exon 12), calreticulin (CALR), myeloproliferative leukaemia virus oncogene (MPL), and breakpoint cluster region-Abelson kinase 1 (BCR::ABL1) was conducted from 01 January 2018 to 31 May 2023. Data were retrieved from the National Health Laboratory Service and analysed for associations with age and gender using Fisher's Exact Test or Pearson's Chi-Square Test (p < 0.05). Results: A total of 8934 patient records were analysed; 58% were male patients and 42% female patients, with a mean age of 50 ± 17 years. Among sequence variant changes, 18.2% of MPN cases were positive for BCR::ABL1, 8.5% for JAK-2 p.V617F, 0.5% for CALR, 0.04% for MPL, and none for JAK-2 exon 12. BCR::ABL1 showed equal sex distribution, while JAK-2 p.V617F increased with age and showed slight female predominance (p = 0.002). CALR and MPL frequencies were too low for meaningful association testing. Conclusion: BCR::ABL1 was the most frequent abnormality, especially in younger age groups, whereas JAK-2 p.V617F was linked to increasing age and female predominance. What this study adds: MPN genetic testing in South Africa predominantly targeted male patients (ratio 1.4:1). BCR::ABL1 was the most common abnormality, particularly in individuals aged 18 to 49 years, while JAK-2 p.V617F showed a slight female predominance (1:1.2).