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Purpose: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) are determinants of treatment and mortality for patients with breast cancer (BC). In East Africa, the estimated 5-year survival (37.7%) is far lower than the US average (90%). This meta-analysis investigates BC receptor subtypes within five East African countries to ascertain cross-country patterns and prioritize treatment needs., Methods: From a PubMed search, January 1, 1998-June 30, 2019, for all English-only BC articles for Ethiopia, Kenya, Rwanda, Tanzania, and Uganda, eligible studies had receptor distributions for female BC samples ≥ 30 patients. Outcomes were proportions of ER+, PR+, and HER2-positive (HER2+), and/or molecular subtypes. Data included study characteristics and mean or median patient age. Using metaprop , Stata 16, we estimated pooled proportions (ES) with 95% CIs and assessed heterogeneity., Results: Among 36 BC studies with receptor data, 21 met criteria. Weighted mean age was 47.5 years and median, 48. Overall ES were as follows: 55% for ER-positive (ER+) (95% CI, 47 to 62), 23% for HER2+ (95% CI, 20 to 26), and 27% for triple-negative BC (TNBC) (95% CI, 23 to 32)., Conclusion: We found differences between countries, for example, lower distribution of TNBC in Ethiopia (21%) compared with Uganda (35%). ER+, the dominant BC subtype overall at 55%, emphasizes the need to prioritize endocrine therapy. Overall proportions of HER2+ BC (with or without ER+ or PR+), 23%, approached proportions of TNBC, 27%, yet HER2 testing and treatment were infrequent. Testing and reporting of receptor subtypes would promote delivery of more effective treatment reducing the mortality disparity.

The Maasai are a pastoral people in Kenya and Tanzania, whose traditional diet of milk, blood and meat is rich in lactose, fat and cholesterol. In spite of this, they have low levels of blood cholesterol, and seldom suffer from gallstones or cardiac diseases. Field studies in the 1970s suggested that the Maasai have a genetic adaptation for cholesterol homeostasis. Analysis of HapMap 3 data using Fixation Index (Fst) and two metrics of haplotype diversity: the integrated Haplotype Score (iHS) and the Cross Population Extended Haplotype Homozygosity (XP-EHH), identified genomic regions and single nucleotide polymorphisms (SNPs) as strong candidates for recent selection for lactase persistence and cholesterol regulation in 143-156 founder individuals from the Maasai population in Kinyawa, Kenya (MKK). The non-synonmous SNP with the highest genome-wide Fst was the TC polymorphism at rs2241883 in Fatty Acid Binding Protein 1(FABP1), known to reduce low density lipoprotein and tri-glyceride levels in Europeans. The strongest signal identified by all three metrics was a 1.7 Mb region on Chr2q21. This region contains the genes LCT (Lactase) and MCM6 (Minichromosome Maintenance Complex Component) involved in lactase persistence, and the gene Rab3GAP1 (Rab3 GTPase-activating Protein Catalytic Subunit), which contains polymorphisms associated with total cholesterol levels in a genome-wide association study of >100,000 individuals of European ancestry. Sanger sequencing of DNA from six MKK samples showed that the GC-14010 polymorphism in the MCM6 gene, known to be associated with lactase persistence in Africans, is segregating in MKK at high frequency (∼58%). The Cytochrome P450 Family 3 Subfamily A (CYP3A) cluster of genes, involved in cholesterol metabolism, was identified by Fst and iHS as candidate loci under selection. Overall, our study identified several specific genomic regions under selection in the Maasai which contain polymorphisms in genes associated with lactase persistence and cholesterol regulation.