Abstract 2247: Evaluation of multidrug resistant genes among breast cancer patients in Ghana

Abstract

Abstract Background: Breast cancer (BC) is a leading cause of cancer death in Ghana and around the world. Ghanaian women are diagnosed at younger ages with the more aggressive Triple Negative BC (TNBC) subtype where West African ancestry is associated with advanced BC diagnosis and higher mortality rates compared to age-matched women of European ancestry. Genomic comparisons of BC tumors from women of African and European ancestry show differences in frequencies of single nucleotide polymorphisms (SNP) and copy number variations. These differences may contribute to disparities in disease and treatment outcomes observed in women of African ancestry. Chemotherapy plays a major role in treatment of recurrent and metastatic BC. Long-term BC survival remains poor especially in Africa due to multidrug resistance (MDR). MDR has been associated with binding cassette (ABC) protein transporters. ABCB1, ABCC1 and ABCG2 are ABC transporter genes that code for proteins involved in drug efflux. We hypothesize that SNPs in ABC transporter genes may alter their physiological protective role and increase risk of MDR, treatment failure and death among BC patients. Preliminary dataWe explored gene expression profiles of ABCB1, ABCC1 and ABCG2 in an African ancestry-enriched subset of women with TNBC (ICSBCS cohort: Ghanaian n = 6, African American (AA) n = 9, Ethiopian n = 11). Preliminary data showed significantly higher expression of ABCC1 among Ghanaian and AA patients compared to Ethiopians, and a significant positive correlation with African ancestry. ABCB1 and ABCG2 showed lower expression in all three groups (ns).To study the relationship between ABC transporter gene SNPs and MDR, we have collected data over a 3-year period (2019-2021) from the Oncology Department of the Komfo Anokye Teaching Hospital in Ghana. The overall prevalence of BC recurrence was 3.4% (CI = 2.5 - 4.7%), and prevalence of metastatic BC was 47.6% (CI = 44.6 - 50.6%). Methodology: SNPs in ABC transporter genes will be obtained from 150 consented female BC patients who have undergone chemotherapy. We will compare genotype frequencies among patients with disease recurrence and/or metastasis (n = 100) to those with no disease recurrence or metastasis (n = 50). Single-plex genotyping of the ABC gene SNPs will be completed using a real-time PCR allelic discrimination assay. Conclusion: ABCC1 has been established to be associated with African ancestry. Determining the association of ABC gene SNPs and MDR among Ghanaian BC patients will provide further information on allelic variants and their effects on BC treatment outcomes. Citation Format: Gloria Agyekum Boaitey, Rachel Martini, Melissa B. Davis, Lisa Newman, Brian Stonaker, Linda Ahenkorah Fondjo, Christian Obirikorang, Ernest Osei Bonsu, Ernest Adjei, Ishmael Kyei, Mavis Bobie Ansah, Mahteme Bekele, Timothy Chu, Nicolas Robine. Evaluation of multidrug resistant genes among breast cancer patients in Ghana [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2247.