Campos, Opeyemi Christianah De

Abstract Background: Prostate cancer (PCa) is the leading cause of cancer-related deaths globally and disproportionately affects men of African ancestry. African men often present at younger ages and with more aggressive disease, and approximately half of the PCa risk has been attributed to genetic factors. Africa is the most genetically diverse region of the world, and even within the continent, populations show important differences in allele frequencies and patterns of pathogenic variation. Despite this diversity, African men remain underrepresented in genomic studies, creating significant gaps in knowledge that limit precision medicine efforts. Methods: A total of 182 prostate cancer patients were recruited from teaching hospitals in Benin, Côte d’Ivoire, Ghana, Kenya and Nigeria. 50 cancer susceptibility genes using the Aviseq ONCO50 panel and the Illumina MiSeq platform. Variant calling was performed using an in-house Snakemake workflow, followed by additional bioinformatic steps to distinguish true PMS2 variants from PMS2CL-related artifacts. Pathogenicity assessment relied on annotations from ClinVar and LOVD databases. Results: Pathogenic and likely pathogenic variants were detected in 31.3% of the study group identified in 26 genes. The five most frequently altered genes were RAD50, PTCH1, MSH6, MUTYH, and NF1. Nigerian patients accounted for 52.6 percent of all pathogenic variants, with recurrent alterations observed in MSH6, MUTYH, NF1, and PTCH1. In contrast, pathogenic BRCA1 and BRCA2 variants were observed primarily in patients from Kenya, Benin, and Côte d’Ivoire. Several frameshift, nonsense, and splice-site variants identified in this study have not been previously reported in African populations.[SR1] Conclusion: This study provides one of the most detailed assessments of inherited cancer susceptibility gene variants in African PCa patients. The findings reveal substantial regional variation in the spectrum of pathogenic variants and highlight population-specific genomic signatures that may contribute to the unequal burden of PCa in men of African ancestry. These data emphasize the importance of expanding genomic research efforts within Africa to strengthen precision oncology and reduce global PCa disparities. Citation Format: Abimbola F. Onyia, Freeman Okwuchi, Opeyemi C. De Campos, Sylvester Divine, Olutola Olasehinde, Ayinde Yahaya, Ayo Salako, Aminu Zakari, Iya Bassey, Nicholas Titiloye, Bernard Petershie, Isidore GANDAHO, Luc Brun, Tore Sanni, Safiatou Coulibaly, Noel Coulibaly, Michael Fakayode, Coulibaly Issoufou, Valérie Gbonon, Kouame Benjamin, Yao Evrard, Peter Coleman, Ayun Cassell, Victor Ajumbo, Lilac Wattanga, Benson Ochieng Nyambega, Folakemi T. Odedina, Solomon Rotimi. Targeted sequencing of common cancer susceptibility genes reveals germline variants in African prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6289.

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition characterized by plasma cell production of monoclonal (M) protein and is a requisite precursor to multiple myeloma (MM). African American (AA) individuals have a two-fold higher incidence of MGUS and MM compared to White individuals. However, data are limited on individuals from Africa, especially using sensitive MGUS detection methods. We examined the prevalence of MGUS in a sample of the general population in Nigeria. Individuals aged 40 and over (n=343) were recruited through health promotion events in Ado-Odo Ota Local Government Area of Ogun State, Nigeria, and provided informed consent, a blood sample, and a short questionnaire. Serum was screened at Mayo Clinic for heavy chain (HC)-MGUS using the matrix-assisted laser desorption/ionization-time of flight (Mass-Fix) assay, which has high sensitivity for detection of M-proteins; serum free light chains (FLC) were also measured. FLC was abnormal if the kappa (>0.26 mg/dL) or lambda (>0.33 mg/dL) light chain (LC) was elevated and FLC ratio (kappa/lambda) was outside the reference range (0.26-3.10). LC-MGUS was defined as an abnormal FLC in the absence of a HC. Age- and sex-adjusted prevalence rates were directly standardized to 2010 United States (US) population for comparison to published studies. Logistic regression was used to examine the association of age, sex, and BMI with HC-MGUS. The mean age of participants was 55 years (SD=10.9), and 74.6% were female. Of these, 216 (63%) had both parents from the Yoruba tribe, 89 (26%) from the Igbo tribe and 38 (11%) from other tribes. Overall, 33 participants (9.6%) had HC-MGUS, with 8 (2.3%) having an M-protein above 0.2 g/dL; 6 (1.7%) had LC-MGUS. HC-MGUS was predominantly IgG isotype (48.5%), followed by IgA (27.3%), biclonal (15.2%) and IgM (9.0%). Prevalence of HC-MGUS was 8.3% for ages 40-49, 7.7% ages 50-69 and 22% ages 70 and above. Standardized to the US population, age and sex adjusted MGUS prevalence ages 50 and older was 17.3% (95% CI: 9.8%-24.9%) and HC-MGUS was 14.7% (95% CI: 7.7%-21.8%), similar to previously published rates of HC-MGUS using Mass-Fix screening of AA individuals (16.5%, 95% CI: 12.2%-20.8%) (PMID: 35316833). In models that included age, sex and BMI, older age was positively associated with HC-MGUS (OR=3.1, 95% CI: 1.1-8.7 for ages 70+ compared to <50), while female sex (OR=0.53, 95% CI: 0.24-1.2) and overweight/obesity (OR=0.34, 95% CI: 0.16-0.75 for BMI > 25 vs. <25) were inversely associated with HC-MGUS. We observed similar prevalence of HC-MGUS at ages 50 and above among Western Nigerian and AA populations when screened using mass-spectrometry. Older age was positively associated with HC-MGUS while overweight and obesity were inversely associated. Studies of MGUS in indigenous African populations may provide insight to unique cancer risk factors compared to other populations. Citation Format: Celine M. Vachon, Cristine Allmer, Danelle Moonen, Aaron Norman, Joselle Cook, Susan Slager, Oluwakemi A. Rotimi, Opeyemi C. De Campos, Titilope M. Dokumu, David Murray, Shaji Kumar, Elizabeth Brown, Linda B. Baughn, Solomon Rotimi. Prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a Western Nigerian population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3455.