ABSTRACT
INTRODUCTION: Obtaining informed consent from study participants and disseminating the findings responsibly is a key principle required for ethically conducted clinical and genetic research. Reports from African researchers providing feedback on insights gained during the return of whole exome sequencing (WES) results to breast cancer patients treated in resource-limited settings is lacking. AIM: The empirical process used to fill this gap in relation to BRCA1/2 variant detection using WES provided unique insights incorporated into a pathology-supported genetic testing algorithm for return of research results to Kenyan breast cancer patients. METHODS: The Informed consent form approved by the Moi Teaching and Referral Hospital in Kenya was adopted from a translational research study conducted in South Africa. Initially, the informed consent process was piloted in 16 Kenyan female patients referred for breast surgery, following a community-based awareness campaign. A total of 95 female and two male breast cancer patients were enrolled in the study from 2013 to 2016. Immunohistochemistry (IHC) results of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status were obtained from hospital records. DNA of patients with a family history of cancer was extracted from saliva and screened for pathogenic variants in the BRCA1/2 genes as the first step using WES. RESULTS: Ten patients approached for participation in this study declined to sign the informed consent form. Data on IHC used as a proxy for molecular subtype were available in 8 of 13 breast cancer patients (62%) with a family history of cancer. Five BRCA1/2 variants of uncertain clinical significance were detected, as well as a pathogenic BRCA2 variant (c.5159C > A; S1720∗) in a female patient eligible for return of WES results. CONCLUSION: Experience gained during the qualitative pilot phase was essential to overcome challenges associated with the translation of sophisticated genetic terms into native African languages. Detection of a pathogenic BRCA2 variant in a patient with familial breast cancer, frequently associated with hormone receptor-positive breast carcinoma as reported in this case, led to a high level of confidence on which to base risk management in future. Implementation of new technologies alongside standard pathology provides a practical approach to the application of genomic medicine in Africa.
ABSTRACT
Burkitt's lymphoma (BL) is a frequent childhood B cell non-Hodgkin's lymphoma (NHL) in equatorial Africa associated with infections. Chronic Epstein Barr virus (EBV) infections can lead to host immune stimulation that may trigger genetic translocation(s), neoplastic transformation and proliferation of B cells. We determined EBV immunoglobulin G (IgG) in sera from participants and EBER-1 in tumour sections in confirmed BL cases at Moi Teaching and Referral Hospital (MTRH). A cross sectional study of children with clinical and histology diagnosis of NHL from whom BL status were confirmed by immunohistochemistry (IHC) was carried out. Epstein Barr virus IgG in sera was determine using Enzyme-linked immunosorbant assay, IHC for EBER-1 and MYC protein in tumour sections. Demographic and clinical information were obtained from questionnaires and hospital files respectively. Ninety three percent of sera were EBV IgG positive of which 31.7% were confirmed as BL. All jaw BL tumours and 86.7% of BL tumours carried EBER-1 antigen. Odds ratio of EBER-1 positive was 1.39, 95% CI: 0.16-12.19 in BL tumours regardless of age or gender. EBV infection among the study participants may be associated with BL, however, EBER-1 and MYC negative in BL tumours suggest alternative BL pathogenesis or variant.