Abstract B047: Biochemical parameters of prostate cancer patients in Nigeria

The screening of biochemical parameters of cancer patients and their development into reliable and specific diagnostic and prognostic biomarkers has been reported in several studies. The biochemical signature of prostate cancer patients in Nigeria may vary from others and can serve as important leads in discovery of new biomarkers for the disease. This will ultimately provide more information on the specific causes and prognosis of the disease as well as improve its diagnosis and management. This study examined some biochemical parameters including alanine transaminase (ALT), alkaline phosphatase (ALP), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TRIG), reduced glutathione (GSH), lipid peroxidation and peroxidase (POD) in the plasma of prostate cancer patients and controls. The data obtained indicate that there were no significant differences in the ALT, LDL, HDL, and POD while ALP and TRIG were significantly increased. Also, there was a significant reduction in GSH. This indicates the possible implication of ALP, TRIG, and GSH in prostate cancer disease in Nigeria and their potential to be further developed into diagnostic and prognostic biomarkers

Abstract B048: Androgen metabolism and incidence of prostate cancer in Nigeria

The risk of prostate cancer among blacks, especially of Nigerian descent, is higher than other races. This could be attributed to biologic and genetic variability. The role of androgen metabolism in prognosis of prostate cancer has been delineated and reported. One of the enzymes involved in androgen metabolism is CYP3A4, which has not been studied in Nigerian men afflicted with prostate cancer. Racial differences in this functional gene may contribute to variations in incidence of prostate cancer across ethnic divides. Therefore, identifying a diagnostic and prognostic biomarker such as CYP3A4 polymorphism for prostate cancer in black men will improve the treatment and management of the disease. In this study, we investigated the genotypes of CYP3A4 of prostate cancer patients from Nigeria for possible correlation to the high incidence of the disease in Nigerian men. The results obtained showed a preponderance of the GG genotypes, which indicates a possible correlation between this genotype of CYP3A4 and higher risk of prostate cancer among Nigerian men

Abstract B047: Biochemical parameters of prostate cancer patients in Nigeria

The screening of biochemical parameters of cancer patients and their development into reliable and specific diagnostic and prognostic biomarkers has been reported in several studies. The biochemical signature of prostate cancer patients in Nigeria may vary from others and can serve as important leads in discovery of new biomarkers for the disease. This will ultimately provide more information on the specific causes and prognosis of the disease as well as improve its diagnosis and management. This study examined some biochemical parameters including alanine transaminase (ALT), alkaline phosphatase (ALP), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TRIG), reduced glutathione (GSH), lipid peroxidation and peroxidase (POD) in the plasma of prostate cancer patients and controls. The data obtained indicate that there were no significant differences in the ALT, LDL, HDL, and POD while ALP and TRIG were significantly increased. Also, there was a significant reduction in GSH. This indicates the possible implication of ALP, TRIG, and GSH in prostate cancer disease in Nigeria and their potential to be further developed into diagnostic and prognostic biomarkers

Spectrum of musculo-skeletal disorders in sickle cell disease in Lagos, Nigeria

<p>Abstract</p> <p>Background</p> <p>Sickle cell anemia (SCA) is a common genetic disease in Nigeria. Past studies from West Africa focused on isolated aspects of its medical and surgical presentations. To the best of our knowledge, the musculo-skeletal presentations amongst Nigerians with SCA have not been documented in a single all encompassing study. This work aims to prospectively document the musculo-skeletal disease burden among SCA patients.</p> <p>Methods</p> <p>In a prospective study of 318 consecutive patients with genotype-confirmed SCA at the Lagos University Teaching Hospital (LUTH), the musculo-skeletal pathologies, anatomic sites, grade of disease, age at presentation and management outcome were recorded over a one-year period. Data obtained were analyzed using Epi-Info software version 6.0. Data are presented as frequencies (%) and mean values (SD) as appropriate.</p> <p>Results</p> <p>The HbSS genotype occurred in 296 (93.0%), while 22 (7.0%) were HbSC. 100 (31.4%) patients with average presenting haemoglobin concentration of 8.2 g/100 ml in the study group, presented with 131 musculo-skeletal pathologies in 118 anatomic sites. Osteomyelitis 31 (31%) and septic arthritis 19 (19%) were most commonly observed in children less than 10 years. Skin ulcers and avascular necrosis (AVN) occurred predominantly in the older age groups, with frequencies of 13 (13.0%) and 26 (26.0%) respectively. 20 (71.5%) of diagnosed cases of AVN presented with radiological grade 4 disease. The lower limbs were involved in 84 (71.1%) of sites affected. Lesions involving the spine were rare 11 (0.9%). Multiple presentations occurred in 89 (28.0%) of patients; 62 (69.7%) of which were children below 10 years.</p> <p>Conclusions</p> <p>Musculo-skeletal complications are common features of sickle cell anaemia seen in 31.4%. Infectious aetiologies predominate with long bones and joints of lower limbs more commonly affected by osteomyelitis and septic arthritis. Healthcare providers managing SCA should be aware of the potential morbidity and mortality of these conditions to ensure early diagnosis and adequate management.</p

Abstract B048: Androgen metabolism and incidence of prostate cancer in Nigeria

The risk of prostate cancer among blacks, especially of Nigerian descent, is higher than other races. This could be attributed to biologic and genetic variability. The role of androgen metabolism in prognosis of prostate cancer has been delineated and reported. One of the enzymes involved in androgen metabolism is CYP3A4, which has not been studied in Nigerian men afflicted with prostate cancer. Racial differences in this functional gene may contribute to variations in incidence of prostate cancer across ethnic divides. Therefore, identifying a diagnostic and prognostic biomarker such as CYP3A4 polymorphism for prostate cancer in black men will improve the treatment and management of the disease. In this study, we investigated the genotypes of CYP3A4 of prostate cancer patients from Nigeria for possible correlation to the high incidence of the disease in Nigerian men. The results obtained showed a preponderance of the GG genotypes, which indicates a possible correlation between this genotype of CYP3A4 and higher risk of prostate cancer among Nigerian men

Strengthening Capacity for Prostate Cancer Early Diagnosis in West Africa Amidst the COVID-19 Pandemic: A Realist Approach to Rethinking and Operationalizing the World Health Organization 2017 Guide to Cancer Early Diagnosis

Two years after SARS-CoV-2 (COVID-19) was declared a global public health emergency, the restoration, at least, to the pre-pandemic level of early diagnostic services for prostate cancer has remained enormously challenging for many health systems, worldwide. This is particularly true of West Africa as the region grapples also with the broader impacts of changing demographics and overly stretched healthcare systems. With the lingering COVID-19 crisis, it is likely that the current trend of late prostate cancer diagnosis in the region will worsen with a concomitant increase in the burden of the disease. There is, therefore, a compelling need for innovative and evidence-based solutions to de-escalate the current situation and forestall the collapse of existing structures supporting early prostate cancer diagnosis in the region. In this viewpoint, we make a case for the operationalization of the World Health Organization (WHO) guide to early cancer diagnosis to strengthen the capacity for early prostate cancer diagnosis in West Africa using a realist approach, drawing on participatory health research and evidence-based co-creation. Ultimately, we demonstrate the potential for developing COVID-19 responsive and context-specific models to optimize patient navigation/journey along the essential steps of the World Health Organization guide to early cancer diagnosis

Tumor only analysis of whole exome sequencing from a multi-institutional Nigerian prostate cancer cohort reveals DNA repair genes associated with African ancestry

Men of African ancestry (MAA) have the highest global incidence and mortality of prostate cancer (PCa); however, the biology underlying this harsh disease presentation remains poorly understand, largely due to Africans and people within the African diaspora being under-represented in genomics research. MAA are younger at diagnosis, have higher tumor volume at diagnosis and have higher tumor aggression compared to European American men. Additionally, genomic profiling continues to show that PCa etiology and phenotype are influenced by higher amounts of African ancestry and that West African ancestry is associated with unique genomic alterations. Herein we utilize whole exome sequencing of a unique cohort of 45 advanced stage, treatment naïve Nigerian primary PCa tumors and 11 unmatched non-tumor tissue to compare genomic variants with African (AA) and European (EA) American TCGA PCa tumors. Nigerian samples were collected from 6 sites in central and southwest Nigeria. After whole exome sequencing, samples were processed using GATK best practices. Four genes [BRCA1 (100%), BARD1 (45%), BRCA2 (27%) and PMS2 (18%)] had germline variants in at least two Nigerian non-tumor samples. Across 111 germline variants, the AA cohort reflected a pattern [BRCA1 (68%), BARD1 (34%), BRCA2 (28%) and PMS2 (16%)] similar to Nigerian samples. Of the most frequently mutated genes, BRCA1 showed a statistically (p ≤ 0.05) higher mutation frequency in MAA. Disaggregating gene level mutation frequencies by variant revealed both ancestry linked and Nigerian specific germline variant patterns. Driven by rs799917, BRCA1 showed increasing mutation frequency as African admixture increased. BRCA2_rs11571831 was only present in MAA and BRCA2_rs766173 was increased in Nigerian men. 133 somatic variants were present in 26 PCa associated genes within the Nigerian tumor cohort. Nine genes [BRCA2 (27%), APC (20%), ATM (20%), BRCA1 (13%), DNAJC6 (13%), EGFR (13%), MAD1L1 (13%), MLH1 (11%) and PMS2 (11%)] showed mutation frequencies above 10%. Compared to TCGA cohorts, BRCA2, APC and BRCA1 showed statistically significant increases in Nigerian tumors. The Nigerian cohort variant pattern shared similarities (cosign similarities ≥ 0.734) with COSMIC signatures 5 and 6 and mutated genes showed significant (q < 0.001) GO and functional enrichment in mismatch repair and non-homologous repair deficiency (HRD) pathways. Here, we show that variants in DDR genes are increased in Nigerian PCa and that a portion of those variants correlate with increased African ancestry. Moreover, we identify variants of unknown significance that may contribute to population specific routes of tumorigenesis and treatment. These results present the most comprehensive characterization of the Nigerian PCa exome to date and further highlight the need to increase study population diversity

Review of prostate cancer research in Nigeria

Prostate cancer (CaP) disparities in the black man calls for concerted research efforts. This review explores the trend and focus of CaP research activities in Nigeria, one of the ancestral nations for black men. It seeks to locate the place of the Nigerian research environment in the global progress on CaP disparities. Literature was reviewed mainly through a Pubmed search with the terms “prostate cancer”and “Nigeria”, as well as from internet and hard copies of journal pages

Abstract A030: International Registry for Men with Advanced Prostate Cancer (IRONMAN) study: The Nigerian experience

Abstract Background: Prostate cancer (CaP) is a global disease with the greatest burden among Black men, including sub-Saharan African men. The International Registry to Improve Outcomes in Men with Advanced Prostate Cancer (IRONMAN) was established by the Prostate Cancer Clinical Trials Consortium (PCCTC) as a prospective, international cohort of men with advanced cancer. The goal of the study is to establish a population-based CaP registry and recruit patients across academic and community practices globally. The Prostate Cancer Transatlantic Consortium (CaPTC) joined the IRONMAN project in 2020 with active sites in Nigeria. Aim: The overall aims of the IRONMAN cohort are to develop a global picture of advanced CaP and facilitate a better understanding of the disease relative to clinical and molecular disease subtypes, treatment patterns, therapeutic regimens with associated adverse events, patient experiences and predictors of responses and unmet needs in treatment. This report presents the experiences of a low-resourced country, Nigeria, in launching the IRONMAN study. Methods: CaPTC officially launched the IRONMAN study in Nigeria in 2021. Set up included obtaining national ethics approval, training of the multidisciplinary teams from 4 sites and 7 sub-sites, and activation of all sites. Data collection includes baseline and follow-up data from patients. Patients will be followed prospectively for overall survival, clinically significant adverse events, comorbidities, changes in cancer treatments, and patient-reported outcome measures (PROMs). Physician Questionnaires are also collected from all participating sites. PCCTC maintains close monitoring of the study Results: By the 9th month of the study, the Nigerian sites had recruited 54 patients who have been followed up for 3 to 9 months. There were initial challenges with start up facilities and manpower skills. The training programs have developed a multi-disciplinary team of clinical researchers across multiple institutions, now primed to conduct clinical trials. Facilitated by CaPTC, the study has also helped strengthened multi-center national and international collaborations. Additionally, there are now several clinical trials ready sites in Nigeria, facilitated by audit of the research infrastructures across Nigeria. An added benefit is that there is an opportunity to have molecular typing of CaP in Nigeria. Conclusion: The inclusion of low-resourced sites in international studies can significantly help to improve research workforce and research capacity. The CaPTC IRONMAN sites in Nigeria are top recruiting sites for the study, underscoring the benefits of biomedical research investments in Low and Middle Income Countries. The data from Nigeria would help to better understand CaP in Black men globally. Citation Format: Ademola Alabi Popoola, Chidiebere N. Ogo, Omolara Fatiregun, Mohammed Dogo, Solomon O. Rotimi, Folakemi Odedina, Prostate Cancer Transatlantic Consortium CaPTC Investigators. International Registry for Men with Advanced Prostate Cancer (IRONMAN) study: The Nigerian experience [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A030.</jats:p