Browsing by Author "Olopade, O. I."

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"Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features"
(Nature Research, 2018) Pitt, J. J.; Riester, M.; Zheng, Y.; Yoshimatsu, T. F.; Sanni, A.; Oluwasola, O.; Veloso, A.; Labrot, E.; Wang, S.; Odetunde, A.; Ademola, A.; Okedere, B.; Mahan, S.; Leary, R.; Macomber, M.; Ajani, M.; Johnson, R. S.; Fitzgerald, D.; Grundstad, A. J.; Tuteja, J. H.; Khramtsova, G.; Zhang, J.; Sveen, E.; Hwang, B.; Clayton, W.; Nkwodimmah, C.; Famooto, B.; Obasi, E.; Aderoju, V.; Oludara, M.; Omodele, F.; Akinyele, O.; Adeoye, A.||; Ogundiran, T.; Babalola, C.; MacIsaac, K.; Popoola, A.; Morrissey, M. P.; Chen, L. S.; Wang, J.; Olopade, C. O.; Falusi, A. G.; Winckler, W.; Haase, K.; Van Loo, P.; Obafunwa, J.; Papoutsakis, D.; Ojengbede, O.; Weber, B.; Ibrahim, N.; White, K. P.; Huo, D.; Olopade, O. I.; Barretina, J
Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate breast cancer in diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of breast cancers using 194 patients from Nigeria and 1037 patients from The Cancer Genome Atlas (TCGA). Relative to Black and White cohorts in TCGA, Nigerian HR + /HER2 − tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, and greater structural variation—indicating aggressive biology. GATA3 mutations are also more frequent in Nigerians regardless of subtype. Higher proportions of APOBEC-mediated substitutions strongly associate with PIK3CA and CDH1 mutations, which are underrepresented in Nigerians and Blacks. PLK2, KDM6A, and B2M are also identified as previously unreported significantly mutated genes in breast cancer. This dataset provides novel insights into potential molecular mechanisms underlying outcome disparities and lay a foundation for deployment of precision therapeutics in underserved populations.
Clinicopathological pattern of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 over-expression of epithelial ovarian carcinomas in Nigeria
(Makerere University, Medical School, 2023) Ajani, M. A.; Lawan, A.; Oke, T.; Khramtsova, G.; Nwanji, I.; Salami, A.; Awolude, O.; Ebili, H.; Onwukamuche, M. E.; Sveen, E.; Yoshimatsu, T.; Olopade, O. I.
Background: Ovarian cancer is the leading cause of death from all gynaecological malignancies. Only few biomarkers of epi thelial ovarian cancer (EOC) prognosis have been studied so far among Nigerian patients. Objective: To determine the pattern of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression in patients with EOC seen in Nigeria Materials and Methods: This was a retrospective multicentre study of 102 cases of epithelial ovarian cancers. Relevant clinical information was obtained from hospital-based records in the 3 participating centres. Tissue microarrays were constructed using representative tumour tissue and the ER, PR and HER2 immunohistochemical staining was carried out at the University of Chicago, United States of America. Results: Serous carcinomas predominated (71% of cases). ER positivity was observed in 31.4%, PR positivity in 21.5% and HER2/neu in 16.7% of tumours. Fifty-two percent of tumours were triple negative. Serous tumours were significantly asso ciated with ER positivity (p=0.001). Mean patient age for EOC was 52.6 ± 13.1 years. There were no statistically significant associations between hormone receptor status and histological grade, FIGO staging or survival. Conclusion: Serous tumours were significantly associated with ER expression while non-serous tumours tended to be triple negative.
Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria
(John Wiley & Sons Ltd, 2019) Wang, S. F.; Pitt, J. J.; Zheng, Y.; Yoshimatsu, T. F.; Gao, G.; Sanni, A.; Oluwasola, O.; Ajani, M.; Fitzgerald, D.; Odetunde, A.; Khramtsova, G.; Hurley, I.; Popoola, A.; Falusi, A.; Ogundiran, T.; Obafunwa, J.; Ojengbede, O.; Ibrahim, N.; Barretina, J.; White, K. P.; Huo, D.; Olopade, O. I.
Somatic mutation signatures may represent footprints of genetic and environmental exposures that cause different cancer. Few studies have comprehensively examined their association with germline variants, and none in an indigenous African population. SomaticSignatures was employed to extract mutation signatures based on whole-genome or whole-exome sequencing data from female patients with breast cancer (TCGA, training set, n = 1,011; Nigerian samples, validation set, n = 170), and to estimate contributions of signatures in each sample. Association between somatic signatures and common single nucleotide polymorphisms (SNPs) or rare deleterious variants were examined using linear regression. Nine stable signatures were inferred, and four signatures (APOBEC C>T, APOBEC C>G, aging and homologous recombination deficiency) were highly similar to known COSMIC signatures and explained the majority (60–85%) of signature contributions. There were significant heritable components associated with APOBEC C>T signature (h2 = 0.575, p = 0.010) and the combined APOBEC signatures (h2 = 0.432, p = 0.042). In TCGA dataset, seven common SNPs within or near GNB5 were significantly associated with an increased proportion (beta = 0.33, 95% CI = 0.21–0.45) of APOBEC signature contribution at genome-wide significance, while rare germline mutations in MTCL1 was also significantly associated with a higher contribution of this signature (p = 6.1 × 10−6 ). This is the first study to identify associations between germline variants and mutational patterns in breast cancer across diverse populations and geography. The findings provide evidence to substantiate causal links between germline genetic risk variants and carcinogenesis.
Implementing oncology clinical trials in Nigeria: A model for Capacity building.
(Springer Nature, 2020) Ntekim, A.; Ibraheem, A.; Sofoluwe, A.; Adepoju, T.; Oluwasanu, M.; Aniagwu, M.; Awolude, O.; Balogun,W.; Kotila, K.; Adejumo, P.; Babalola, C. P.; Arinola, G.; Ojengbede, O.; Olopade, C. O.; Olopade, O. I.
Background: There is both higher mortality and morbidity from cancer in low and medium income countries (LMICs) compared with high income countries (HICs). Clinical trial activities and development of more effective and less toxic therapies have led to signi¦ cant improvements in morbidity and mortality from cancer in HICs. Unfortunately, clinical trials remain low in LMICs due to poor infrastructure and paucity of experienced personnel to execute clinical trials. There is an urgent need to build local capacity for evidence based treatment for cancer patients in LMICs. Methods: We conducted a survey at facilities in four Teaching Hospitals in South West Nigeria using a checklist of information on various aspects of clinical trial activities. The gaps identi¦ ed were addressed using resources sourced in partnership with investigators at HIC institutions. Results: De¦ cits in infrastructure were in areas of patient care such as availability of oncology pharmacists, standard laboratories and diagnostic facilities, clinical equipment maintenance and regular calibrations, trained personnel for clinical trial activities, investigational products handling and disposals and lack of standard operating procedures for clinical activities. There were two GCP trained personnel, two study coordinators and one research pharmacist across the four sites. Interventions were instituted to address the observed de¦ cits in all four sites which are now well positioned to undertake clinical trials in oncology. Training on all aspects of clinical trial was also provided. Conclusions: Partnerships with institutions in HICs can successfully identify, address, and improve de¦ cits in infrastructure for clinical trial in LMICs. The HICs should lead in providing funds, mentorship and training for LMIC institutions to improve and expand clinical trials in LMIC countries.
Oncology Training Needs Assessment Among Health Care Professionals in Nigeria
(American Society of Clinical Oncology (ASCO), 2022) Adejumo, P. O.; Oluwasanu, M. M.; Ntekim, A.; Awolude. O. A.; Kotila, O. A.; Aniagwu T.; Brown B. J.; Dzekem, B. S.; Duncan, S.; Tito Ilori, M.; Ajani O.; Lee, S. M.; Babalola. C. P.; Ojengbede, O.; Huo. D.; Hammad, N.; Olopade, O. I.
PURPOSE This study investigated the status of training and preparedness for oncology practice and research and degree of interprofessional collaboration among health care professionals in the six geopolitical regions of Nigeria. METHODS A convergent parallel mixed methods design was used. Three hundred seventeen respondents completed a three-part, online questionnaire. Self-rated competencies in oncology research (26 items), oncology practice (16 items), and interprofessional collaboration (nine items) were assessed with a one- to fivepoint Likert scale. Six key informant and 24 in-depth interviews were conducted. Descriptive statistics, analysis of variance, and pairwise t-test were used to analyze the quantitative data, whereas thematic analysis was used for the qualitative data. RESULTS Respondents were mostly female (65.6%) with a mean age of 40.5 6 8.3 years. Respondents include 178 nurses (56.2%), 93 medical doctors (29.3%), and 46 pharmacists (14.5%). Self-assessed competencies in oncology practice differed significantly across the three groups of health care professionals (F = 4.789, P = .009). However, there was no significant difference across professions for competency in oncology research (F = 1.256, P = .286) and interprofessional collaboration (F = 1.120, P = .327). The majority of respondents (267, 82.4%) felt that educational opportunities in oncology-associated research in the country are inadequate and that this has implications for practice. Key training gaps reported include poor preparedness in data analysis and bioinformatics (138, 43.5%), writing clinical trials (119, 37.5%), and writing grant/research proposals (105, 33.1%). Challenges contributing to gaps in cancer research include few trained oncology specialists, low funding for research, and inadequate interprofessional collaboration. CONCLUSION This study highlights gaps in oncology training and practice and an urgent need for interventions to enhance interprofessional training to improve quality of cancer care in Nigeria. These would accelerate progress toward strengthening the health care system and reducing global disparities in cancer outcomes.
The global role, impact, and limitations of Community Health Workers (CHWs) in breast cancer screening: a scoping review and recommendations to promote health equity for all
(Taylor & Francis Group, 2021) Hand, T.; Rosseau, N. A.; Stiles, C. E.; Sheih, T.; Ghandakly, E.; Oluwasanu, M.; Olopade, O. I.
Introduction: Innovative interventions are needed to address the growing burden of breast cancer globally, especially among vulnerable patient populations. Given the success of Community Health Workers (CHWs) in addressing communicable diseases and non-commu-nicable diseases, this scoping review will investigate the roles and impacts of CHWs in breast cancer screening programs. This paper also seeks to determine the effectiveness and feasi-bility of these programs, with particular attention paid to differences between CHW-led interventions in low- and middle-income countries (LMICs) and high-income countries (HICs). Methods: A scoping review was performed using six databases with dates ranging from 1978 to 2019. Comprehensive definitions and search terms were established for ‘Community Health Workers’ and ‘breast cancer screening’, and studies were extracted using the World Bank definition of LMIC. Screening and data extraction were protocolized using multiple independent reviewers. Chi-square test of independence was used for statistical analysis of the incidence of themes in HICs and LMICs. Results: Of the 1,551 papers screened, 33 were included based on inclusion and exclusion criteria. Study locations included the United States (n=27), Bangladesh (n=1), Peru (n=1), Malawi (n=2), Rwanda (n=1), and South Africa (n=1). Three primary roles for CHWs in breast cancer screening were identified: education (n=30), direct assistance or performance of breast cancer screening (n=7), and navigational services (n=6). In these roles, CHWs improved rates of breast cancer screening (n=23) and overall community member knowledge (n=21). Two studies performed cost-analyses of CHW-led interventions. Conclusion: This review extends our understanding of CHW effectiveness to breast cancer screening. It illustrates how CHW involvement in screening programs can have a significant impact in LMICs and HICs, and highlights the three CHW roles of education, direct perfor-mance of screening, and navigational services that emerge as useful pillars around which governments and NGOs can design effective programs in this area.
Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes
(Nature Research, 2021) Ansari-Pour, N.; Zheng, Y.; Yoshimatsu, T. F.; Sanni, A.; Ajani, M.; Reynier, J.-B.; Tapinos, A.; Pitt, J. J.; Dentro, S.; Woodard, A.; Rajagopal, P. S.; Fitzgerald, D.; Gruber, A. J.; Odetunde, A.; Popoola, A.; Falusi, A. G.; Babalola, C. P.; Ogundiran, T.; Ibrahim, N.; Barretina, J.; Van Loo, P.; Chen, M.; White, K. P.; Ojengbede, O.; Obafunwa, J.; Huo, D.; Wedge, D. C.; Olopade, O. I.
Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, under scoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.