Publication: Unique Apoptotic Gene Dysregulation in Kenyan Breast Cancer Patients Compared to African American and Caucasian Women
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2025
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Abstract
Background: Kenya records about 6,000 new diagnoses each year of breast cancer (BC), a major
cause of cancer-related deaths in the country. The apoptotic pathway is well studied and proven to
play a crucial role in cancer onset and progression, but studies have not been extensively done on
Kenyan women with BC. The study’s objective was to compare the gene expression patterns of
apoptotic genes in Kenyan women with breast cancer to those of Caucasian women and African
American women based on demography, subtype, and tumour stage.
Methods: Transcriptomic data from 46 African Americans, 66 Caucasians retrieved from The
Cancer Genome Atlas (TCGA), and 60 Kenyan RNA-seq data (45 samples from AIC Kijabe/Aga
Khan hospitals and 15 Triple-Negative Breast Cancer (TNBC) from Gene Expression Atlas (GEO))
were studied. The Kenyan patients were part of a longitudinal BC genomics study in Kenya, and
the TCGA data were retrospectively selected based on availability of RNA-seq data, documented
ethnicity, and tumour stage and subtype classification. HISAT2 v2.2.0 aligned Kenyan transcripts
to the reference genome, and HTSeq-count v2.0.2 determined gene counts. EdgeR v4.2 was used to
analyse differential gene expression, and Enrichr v3.1 and ClusterProfiler v4.0 were used for
enrichment analysis.
Results: The analysis revealed 23 population-specific apoptotic genes differentially expressed
across the 60 Kenyan samples, with 9 upregulated and 14 downregulated. In comparison, 80
upregulated and 25 downregulated unique apoptotic genes were identified in the Caucasian dataset,
while 6 upregulated and 1 downregulated unique apoptotic genes were recorded from the AfricanAmerican dataset. Kenyan BC patients (without controlling for subtype or stage) had a unique
elevation of the anti-apoptotic gene, Insulin-like Growth Factor 1 Receptor (IGF1R). Kenyan
women with Luminal A subtype, compared to other subtypes studied and compared to Caucasian
and African- American women, had a distinct upregulation of Interleukin-1 beta (IL1B). The IL1B
gene prevents the progression and spread of tumour cells in prostate cancer, with over-exposure of
tumour cells to IL1B in vitro leading to resistance to a variety of anticancer medicines in mice. On
the other hand, IGF1R has been associated with poor prognosis in patients with elevated expression
of the gene in Stage I, in non-small-cell lung cancer.
Conclusion: These results highlight population-specific molecular di
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Keywords
Apoptosis, Kenya, Breast cancer