ANALYSIS OF EXPRESSION LEVELS OF APOPTOTIC GENES IN BREAST CANCER AMONG KENYAN, AFRICAN-AMERICAN AND CAUCASIAN WOMEN

Abstract

Breast cancer is the most common type of cancer diagnosed in women worldwide and also one of the highest-ranking causes of cancer-related deaths. The histogenesis of breast cancer is well studied with five different molecular subtypes of breast cancer being identified since the invention of gene array technology: Luminal A, Luminal B, human epidermal growth factor receptor 2 positive (HER2+), Basal-like breast cancers, and Claudin-low breast cancers. While the role of apoptosis in oncogenesis is well documented, the level of dysregulation of apoptotic genes in breast cancer in the Kenyan population is understudied. Moreover, existing research on the role of apoptotic genes and molecular targeted therapeutics in cancer is mainly based on the Caucasian and African-American populations thus lacking the representation of the African specific population. This study aimed to analyze the dysregulation of the apoptotic process among Kenyan women with breast cancer through a comparative evaluation analysis comparing populations, different ages, stages and subtypes of breast cancer. The expression level of apoptotic genes of 60 Kenyan, 66 Caucasian, and 47 African-American transcriptomes of breast tumor and adjacent normal tissues was analyzed. The Kenyan transcripts were aligned to the human reference genome (hg38) using Hisat2 v2.2.0 and gene counts were generated using HTSeq-count v2.0.2. The Caucasian and African-American count matrices were downloaded from The Cancer Genome Atlas (TCGA. The EdgeR v4.2 tool was used for differential expression analysis while enrichment analysis was done using EnrichR v3.1 and Clusterprofiler v4.0 for all three datasets. Comparative analysis of expressed candidate genes was done among Kenyan, Caucasian, and African American Breast Cancer patients and further compared based on subtype, age, and the stage of the disease at the time of diagnosis. The differential expression analysis of tumor and normal adjacent tissue from Kenyan Breast cancer