Browsing by Author "Aje, Eben A."

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    Abstract 999: Spectrum of germline BRCA1/2 gene mutations in Nigerian breast cancer patients
    (Cancer Res (2025) 85 (8_Supplement_1), 2025) Onyia, Abimbola F; Jibrin, Paul; Olatunji-Agunbiade, Temitope; Oyekan, Ademola; Lawal, AbdulRazzaq; Alabi, Adewumi; Sowunm, Anthonia C.; Aje, Eben A.; Ogunniyi, Oluwabusayo B.; Nkom, Ebenezer S.; De Campos, Opeyemi C; Rotimi, Oluwakemi A.; Oyelade, Jelili O.; Rotimi, Solomon O.
    Breast cancer (BC) is the leading cause of cancer-related deaths in Nigerian women, with triple-negative breast cancer (TNBC) being the most prevalent. The TNBC subtype is characterized by mutations in BRCA1 and BRCA2 genes, and germline pathogenic carriers of these mutations have an increased risk for BC. Despite these challenges, the prevalence and spectrum of BRCA1/2 pathogenic variants in the Nigerian population differ, and there is a margin in the local capacity to characterize these variations. Therefore, this study aimed to identify and characterize germline variations in BRCA 1/2 genes in Nigerian BC patients and healthy aged-matched controls to understand the genetic risk profiles of BC in this population. Forty-five BC patients were recruited across four major hospitals in Nigeria and aged-matched with 51 healthy female controls. DNA was extracted from blood samples, followed by targeted sequencing of BRCA 1/2 intronic and exonic regions using the Ampliseq for BRCA panel and the Illumina Miseq Platform. Variant calling was performed, and the clinical significance of identified variants was evaluated on the ClinVar and BRCA exchange databases. Variants of unknown significance (VUS) were assessed using known in silico prediction software, and haplotype analysis was carried out using the Haploview 4.2 software. Pathogenic variants were identified in 6.7% of cases, all exclusive to BC patients. These variants included two BRCA1 variants (3: c.133_134delAA (p.Lys45fs) and c.5324T>A (21: p.Met1775Lys), and one BRCA 2 variant (22: c.8817_8820del (p.Lys2939fs) all found in patients with the TNBC subtype. Additionally, 97 benign or likely benign BRCA1/2 variants were found in both BC and control groups, with notable variants such as the rs799917 identified as a surrogate indicator of ancestry. Eighteen VUS were identified, with four predicted to be damaging by three in silico prediction software. The results of haplotype analysis identified distinct BC haplotypes in Nigerian BC patients. The identification of BRCA1/2 pathogenic variants in Nigerian BC patients, especially those with TNBC, suggests a potential for targeted therapies, such as PARP inhibitors, to improve treatment outcomes in this population. This further highlights the need for increased population-specific screening and the integration of genetic screening into BC management strategies, which could facilitate early detection, personalized treatment plans, and genetic counseling for Nigerian BC patients.
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    Abstract 999: Spectrum of germline BRCA1/2 gene mutations in Nigerian breast cancer patients
    (Cancer Res (2025) 85 (8_Supplement_1):, 2025-04-21) Onyia, Abimbola F.; Jibrin, Paul; Olatunji-Agunbiade, Temitope; Oyekan, Ademola; Lawal, AbdulRazzaq; Alabi, Adewumi; Sowunmi, Anthonia C.; Aje, Eben A.; Ogunniyi, Oluwabusayo B.; Nkom, Ebenezer S.; De Campos, Opeyemi C.; Rotimi, Oluwakemi A.; Oyelade, Jelili O.; Rotimi, Solomon O.
    Breast cancer (BC) is the leading cause of cancer-related deaths in Nigerian women, with triple-negative breast cancer (TNBC) being the most prevalent. The TNBC subtype is characterized by mutations in BRCA1 and BRCA2 genes, and germline pathogenic carriers of these mutations have an increased risk for BC. Despite these challenges, the prevalence and spectrum of BRCA1/2 pathogenic variants in the Nigerian population differ, and there is a margin in the local capacity to characterize these variations. Therefore, this study aimed to identify and characterize germline variations in BRCA 1/2 genes in Nigerian BC patients and healthy aged-matched controls to understand the genetic risk profiles of BC in this population. Forty-five BC patients were recruited across four major hospitals in Nigeria and aged-matched with 51 healthy female controls. DNA was extracted from blood samples, followed by targeted sequencing of BRCA 1/2 intronic and exonic regions using the Ampliseq for BRCA panel and the Illumina Miseq Platform. Variant calling was performed, and the clinical significance of identified variants was evaluated on the ClinVar and BRCA exchange databases. Variants of unknown significance (VUS) were assessed using known in silico prediction software, and haplotype analysis was carried out using the Haploview 4.2 software. Pathogenic variants were identified in 6.7% of cases, all exclusive to BC patients. These variants included two BRCA1 variants (3: c.133_134delAA (p.Lys45fs) and c.5324T>A (21: p.Met1775Lys), and one BRCA 2 variant (22: c.8817_8820del (p.Lys2939fs) all found in patients with the TNBC subtype. Additionally, 97 benign or likely benign BRCA1/2 variants were found in both BC and control groups, with notable variants such as the rs799917 identified as a surrogate indicator of ancestry. Eighteen VUS were identified, with four predicted to be damaging by three in silico prediction software. The results of haplotype analysis identified distinct BC haplotypes in Nigerian BC patients. The identification of BRCA1/2 pathogenic variants in Nigerian BC patients, especially those with TNBC, suggests a potential for targeted therapies, such as PARP inhibitors, to improve treatment outcomes in this population. This further highlights the need for increased population-specific screening and the integration of genetic screening into BC management strategies, which could facilitate early detection, personalized treatment plans, and genetic counseling for Nigerian BC patients.
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    Screening of Germline BRCA1 and BRCA2 Variants in Nigerian Breast Cancer Patients
    (Technology in Cancer Research & Treatment Volume 24, 2025) Onyia, Abimbola F.; Jibrin, Paul; Olatunji-Agunbiade, Temitope; Oyekan, Ademola; Lawal, AbdulRazzaq; Alabi, Adewumi; Sowunmi, Anthonia C.; Aje, Eben A.; Ogunniyi, Oluwabusayo B; Nkom, Ebenezer S.; De Campos, Opeyemi C.; Rotimi, Oluwakemi A.; Oyelade, Jelili O.; Rotimi, Solomon O.
    Background: Breast cancer remains a leading cause of mortality among Nigerian women, with triple-negative breast cancer (TNBC) being particularly prevalent. Variations in BRCA1 and BRCA2 genes remain key risk factors for this disease. However, there are gaps in the frequency and spectrum of these variants in Nigerian populations, as well as a dearth in the local capacity to characterize these variations. Objective: This study aimed at identifying and characterizing the germline variations in BRCA1/2 in Nigerian breast cancer patients and healthy age-matched controls to understand the genetic risk profile of breast cancer in this population. Methods: A prospective case-control study was conducted involving 45 breast cancer patients and 51 controls recruited from four major hospitals. DNA was extracted from blood samples, followed by targeted sequencing of BRCA1/2 exonic and intronic regions using the Ampliseq BRCA panel and Illumina MiSeq platform. Variant calling was performed, clinical significance was evaluated on ClinVar and BRCA Exchange databases, and haplotype analysis was performed using NIH LDlink and Haploview 4.2 software. Results: Pathogenic BRCA1/2 variants were identified in 6.7% of breast cancer patients, all with TNBC and a family history of cancer. Two pathogenic BRCA1 variants were detected: a frameshift deletion BRCA1 c.133_134delAA (p.Lys45 fs) (rs397508857) and a missense variant BRCA1 c.5324T >A (p.Met1775Arg) (rs41293463). A BRCA2 frameshift deletion BRCA2 c.8817_8820del (p.Lys2939 fs) (rs397508010) was also identified. These variants were absent in controls. Haplotype analysis revealed distinct BRCA1 and BRCA2 haplotypes in the breast cancer group. Conclusion: This study identifies key BRCA1/2 pathogenic variants and unique haplotypes in Nigerian breast cancer patients, highlighting the need for population-specific genetic screening. Integrating genetic testing into breast cancer management strategies could facilitate early detection, personalized treatment planning, and genetic counseling in Nigeria.
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    Vitamin D Receptor Polymorphism and its Clinical Relevance in Prostate and Colon Cancer Patients: A Study in a Tertiary Institution in Nigeria
    (Journal of Radiation and Cancer Research, 2025-10) Aje, Eben A.; Sowunmi, Anthonia; Alabi, Adewumi; Agbakwuru, Chidi; Oshikanlu, Bukola; Rotimi, Solomon O.; Bashir, Maryam; Rotimi, Oluwakemi; Habeebu, Muhammad; Bolanle, Adegboyega
    Introduction: This study examines the clinical relevance of Vitamin D receptor (VDR) polymorphisms in prostate and colon cancer patients at NSIA LUTH Cancer Centre, Lagos, Nigeria. With limited African data on Vitamin D’s genetic role in cancer, we investigate its association with cancer susceptibility, grade, and stage. Methods: A total of 142 cases and controls were recruited, including newly diagnosed and treated prostate and colon cancer patients. The study received ethical approval from the Lagos University Teaching Hospital Ethical Committee and was self‑funded. Serum Vitamin D levels were assessed using ELISA, while VDR polymorphisms (Fok1, BsmI, TaqI, and ApaI) were analyzed via restriction fragment length polymorphism‑polymerase chain reaction. Results: The study found a significant association between Vitamin D deficiency and both prostate and colon cancers. Serum Vitamin D levels declined with increasing cancer grade and stage. In colon cancer, Vitamin D levels dropped from 43.8 ng/ml in stage I to 34.9 ng/ml in stage IV. In prostate cancer, a sharp decline was observed from 62.6 ng/ml in stage I to 29.8 ng/ml in stage IV. Patients with low Vitamin D levels had higher cancer risk (odds ratio [OR]: 3.1 for colon cancer; OR: 2.2 for prostate cancer). VDR polymorphism analysis revealed significant associations between cancer cases and specific genotypes: Fok1 (FF), BsmI (Bb), TaqI (tt), and ApaI (aa). Patients with these polymorphisms had lower Vitamin D levels, suggesting a genetic predisposition to cancer progression. Conclusion: This study highlights the impact of Vitamin D deficiency and VDR polymorphisms on prostate and colon cancer biology. The findings emphasize their potential roles in disease progression and suggest further research into Vitamin D supplementation as a protective measure in cancer patients