Rotimi, Solomon O.

Abstract Background: Prostate cancer (PCa) in men is, to date, the number one cause of death from cancer worldwide. PCa has been associated with a large number of lifestyle factors, including unhealthy dietary habits. In particular, diet and nutrition have been shown to play pivotal roles in PCa, and the habitual consumption of certain specific foods like meat cooked at very high temperatures has been implicated. However, this has not been documented among Black men. The aim of this study was to determine the association between dietary patterns and their association with the occurrence of prostate cancer. Method: This is a longitudinal multisite Prostate Cancer Transatlantic Consortium (CaPTC) familial cohort phase 2 study. Participants were Nigerian Black men between 35 and 70 years old who were willing to participate in the study over a 10-year period. For the food variety score, a score of 1 was given for each food item eaten weekly, and the aggregate food variety score was totaled and categorized as ≥54% very good, 45%–53% was good, 36%–44% fair, 18%–35% poor and <18% was very poor. Data were analyzed using descriptive statistics, such as frequency analyses. Chi-square analysis was used to evaluate dichotomous variables to compare groups based on demographic factors and the occurrence of PCa. Multivariate logistic regression was used to determine the specific predictors of the diagnosis of PCa with potential adjustment for the other demographic variables. P-values < 0.05 was set as significant. Results: A total of 780 participants were recruited, with 72.6% reporting no history of cancer. The median age was 47.00 (range: 21-97),16.5% have been diagnosed with Pca, and 1.5% were diagnosed with other Cancers. Age of cancer diagnosis showed that 21% were diagnosed at about 50 years. Participants’ fruit consumption showed that 28.4%, 29%, 39.5%, 23%, 31%, 28.7%, and 39.2, ate apples, mango, citrus, papaya, green banana, tomatoes, and watermelon, weekly, respectively. Fish was the most consumed protein source of animal origin irrespective of the cooking methods categories, such as boiling, frying, grilling, and smoking. The median food variety score was 20 (0-67), with 8.5%, 3.8%,49.3%, and 26.8% classified as good, very good, poor, and very poor, respectively. Multivariate analysis showed that the category of food variety score (P=0.0009), age (P<0.0001), and grilled fish consumption (P=0.0333) were found to be associated with Pca occurrence. Conclusions: The study showed that food variety score, age, and fish consumption were the correlates of prostate cancer occurrence in the population studied. Citation Format: Opeyemi O. Bolajoko, Catherine A. Oladoyinbo, Daniel Lee, Oluwaseyi Toye, Parisa Fathi, Robert Turesky, Ademola Popoola, Iya Bassey, Solomon Rotimi, Paul Jibrin, Chidebere Ogo, Abidemi Omonisi, Adebanji Adeniji, Anthonia Showunmi, Omolara Fatiregun, Ayo Salako, Haruna Nggada, Faruk Mohammed, Ifeoma Okoye, Ernie Kaninjing, Folakemi Odedina. Association between dietary patterns and occurrence of prostate cancer among Nigerian men: The CaPTC Familial Cohort Study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B055.

Abstract Black men are disproportionately affected by prostate cancer (CaP), with limited progress in closing the CaP care and survivorship gaps experienced by Black men compared to other racial/ethnic groups. Unfortunately, there is an uptick in CaP incidence rate in the United States (US) since 2014. As reported by the American Cancer Society, the rising CaP incidence rate indicates a shift towards higher grade and stage during diagnosis. The prostate cancer (CaP) disparities experienced by Black men in the US is a microcosm of the global burden of CaP seen in men of African ancestry. For example, the top ten countries leading CaP mortality in the world are all Black nations in Africa and the Caribbean. The complexity of CaP disparities and the need for a unique approach to better understand and address a complex chronic disease, such as CaP, underscores the need for consortium research that is multilevel, collaborative, translational, and global. Through the Department of Defense funding, we formed an inclusive Cancer Care Research Equity (iCCaRE) for Black Men Consortium to advance health equity and reduce disparities in CaP. Comprising CaP survivors, advocates, scientists, and clinicians, the iCCaRE for Black Men Consortium addresses structural, social and biological determinants of CaP among ethnically diverse Black men globally, including US Black men, West African immigrant men in the US and indigenous West African men. The overall goal of the iCCaRE consortium is to optimize CaP diagnosis experiences, treatment and survivorship based on the Science of Survivorship (SOS). Our central hypothesis is that improving social-determinants of health (SDOH) factors, CaP care and survivorship (CaPCaS)-related factors and mediating biological factors will lead to an improvement in patient-reported outcomes (PROs). This presentation will highlight the structural inequities, societal injustices and biological determinants found to be associated with CaP care and survivorship among Black men. Additionally, we will present the use of Community Living Lab (CoLLab) Health System approach to address inequity in minoritized and marginalized communities. Citation Format: Folakemi Odedina, Roxana Dronca, Kimlin Ashing, Ernest Kaninjing, Solomon Rotimi, Che Ngufor, Arnold Merriweather, iCCaRE Consortium. Science of prostate cancer care and survivorship in black men: Structural, social and biological determinants [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr IA007.

Abstract Background: To date, the disparate burden of prostate cancer (CaP) in Black men (BM) is still poorly understood. More disconcerting is the limited access to effective, culturally tailored behavioral interventions to support BM diagnosed with CaP, especially at the point of prostate cancer diagnosis (PPCD). From the PPCD, the transition to CaP survivorship can be mentally and physically trying, especially for those lacking emotional and financial support. It is important to provide psycho-oncology support, address social determinants of health (SDOH) and make emotional support available to ethnically diverse BM at the PPCD. We are addressing the CaP disparities experienced by BM at the PPCD through the Inclusive Cancer Care Research Equity (iCCaRE) for Black Men Consortium. Aim: As part of the iCCaRE for Black men Consortium, the specific aim of our project is to develop a PPCD-based Augmented Reality (AR) intervention program, the iCCaRE PPCD Virtual Robot Assistant (ViRA). The ViRA is based on the established efficacy of six CaP care and survivorship (CaPCaS) video interventions, and will support BM at the PPCD. Methodology: The efficacy of six CaPCaS videos were established through formative research that included 17 BM in Florida. Based on pre- and post-test design, data were collected from participants using a structured survey tailored to each CaPCaS intervention: Prevention, Detection, Diagnosis, Treatment, Survivorship and Advocacy form. Following the efficacy study, the iCCaRE PPCD ViRA was proposed as one of five iCCaRE Science of Survivorship (S.O.S) projects to improve the quality of life of BM. Results: Most of the participants for the efficacy study reported that they were: US-born BM; married; college educated; earn less than $60,000; retired; have health insurance; have annual health examination; have a regular doctor; and were screened within the last year. The CaPCaS videos were found to be efficacious in improving attitude towards CaP screening, beliefs about CaP screening, perceived behavioral control and CaP knowledge. Participants also rated the quality of the videos high and expressed high satisfaction with the videos. We are currently in the development phase of the PPCD iCCaRE ViRA, which is based on behavioral science and health communications model. The ViRA will provide SDOH navigation services, psycho-oncology support and emotional support. The acceptance and usability of the iCCaRE ViRA will be established at urology clinics in Florida as part of the iCCaRE Consortium HEROICA Phase I study. We will test the central hypothesis that improving SDOH factors and CaPCaS-related factors will lead to an improvement in patient reported outcomes. Conclusion: We established the efficacy of the CaPCaS interventions in supporting BM across the CaP care continuum. The iCCaRE ViRA under development will target intervention at the PPCD and deliver a smart and connected personalized AR-enabled intervention system that will positively impact CaP diagnosis experience of BM. Citation Format: Folakemi Odedina, Che Ngufor, Arnold Merriweather, Deidre Pereira, Jennifer Crook, Fathi Parisa, Roxana Dronca, Ernest Kaninjing, Solomon Rotimi, Kimlin Ashing, Manisha Salinas, Sha’Reff Rashad, John McCall, Ebenezer Erefah, Ayinde Yahaya, Wes Sholes. A point of prostate cancer diagnosis (PPCD) Virtual Robot Assistant (ViRA) intervention for newly diagnosed Black men: An iCCaRE consortium for prostate cancer in Black men project [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 B028.

Abstract Background: A recent report from the AACR has found that black men (BM) men have prostate cancer (CaP) death rates that are more than 2 times those for men of any other race or ethnicity. Yet, BM are less likely to receive cutting-edge, or even standard of care treatment compared to their white counterparts. Limited access to care, transportation, patient perception and medical mistrust, as well as cost of care are major contributing factors. Meeting patients where they are and offering treatment in or closer to their homes should help reduce psychological distress and increase access to care and treatment compliance. As part of the iCCaRE for Black men Consortium, we propose a PCHC model which leverages Mayo Clinic Advanced Care at Home (ACH) program and provides a package of care to support the administration of cancer therapy and/or supportive care/symptom management to CaP patients in their homes by specialist healthcare professionals. The objectives of our pilot study are to understand patients’ choice of therapy in choosing the place of treatment and to evaluate the feasibility and impact of PCHC on clinical outcomes, as well as patient reported-outcomes (PRO) and health related quality of life (HQOL). Methodology: For Aim 1, structured questionnaires are used to assess patient preference for location of therapy, at the infusion center or in the home, as well as perceived difficulties and advantages; follow up qualitative data will be collected through semi-structured interviews to capture patients’ thoughts, feelings, attitudes, and questions towards cancer treatments being administered at home versus in a hospital setting. Aim 2 is an observational study of BM with advanced CaP who are participating in a pragmatic, practice-based randomized clinical trial to track acceptability by and impact of home administration of cancer directed or supportive therapy. Results: For Aim 1, data is used to identify themes regarding perceived advantages and concerns of PCHC and inform our understanding of the proportion of patients who are willing to receive and would benefit from this level of care at home. For Aim 2, the following outcomes are evaluated: (a) time to first ER visit and to first hospitalization; (b) HRQoL and quality-adjusted survival; (c) patient satisfaction and compliance, including home time, adherence with symptom self-reporting and compliance with treatment, level of comfort interacting with the care team by phone or tablet, ability to reach a team member for questions or concerns; (d) cost, including out of pocket cost for patients. Conclusion: Our project will provide data on patient understanding and acceptability of cancer care at home and strategies for overcoming cancer care delivery disparities and barriers of access to care for underserved communities. The expected outcome of our project is that PCHC intervention will positively impact CaP treatment, patients’ access and experience with healthcare by developing a new concept of closer-to home cancer care delivery that will reach more patients in underserved communities. Citation Format: Roxana Dronca, Rohit Rao, Michael Maniaci, Folakemi Odedina, Ernest Kaninjing, Kimlin Ashing, Solomon Rotimi, Manisha Salinas, Sha’Reff Rashad, Arnold Merriweather, John McCall, Ebenezer Erefah, Ayinde Yahaya. Feasibility of patient-centered home care (PCHC) to reduce disparities in Black men (BM) with advanced prostate cancer (CaP): An iCCaRE Consortium for prostate cancer in Black men project [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 B046.

Abstract Background: Sub-Saharan African immigrants (SSAI) in the United States (US) constitute one of the fastest-growing segments of the immigrant population. Between 2010 and 2018, the SSAI population in the US increased by 53%, significantly outpacing the 12% growth rate for the overall foreign-born population in the US during that time frame. For the purposes of this study, we define SSAI as the 2 million individuals living in the US originally from the region of the African continent located south of the Saharan desert. Despite their growing numbers, little is published about the extent to which SSAI adapt to health behaviors more common in the US or remain immersed in the values, beliefs and practices reflective of their country of origin. Importantly, no study has comprehensively examined the social determinants of health factors among this population and its influence on health-seeking behaviors and decision-making regarding prostate cancer care and treatment options. This study employs the social determinant of migrant health framework to examine the impact of immigration on the health-seeking behaviors of SSAI including informed-decision making, psychosocial effects and coping mechanisms. This study will fill the void of research studies that link social determinant of health and immigration among SSAI. Methods: Grounded theory will guide the study design that include in-depth interviews to document the experiences of SSAI relative to health seeking behaviors, care, and treatment. We explore differences and similarities among participants based on country or region of origin in Africa. We employ the social determinants of migrant health framework to better understand the needs of SSAI prostate cancer survivors in the United States and how to effectively support these survivors. Results: We will present findings based on preliminary interviews conducted with SSAI prostate cancer survivors recruited from Florida or Minnesota. Additionally, we will report on the development of a SSAI social determinant of migration model that explains individual and structural factors that impact the health-seeking behaviors and coping mechanisms among this population. We will provide new understanding about specific social determinant of health factors that can be addressed in intervention studies among SSAI in the United States. Conclusion: This study examines the full range of racial, social, environmental, behavioral and structural factors that SSAI prostate cancer survivors experience. It will illuminate the decision-making process and overall quality of care among this understudied population. Citation Format: Ernie Kaninjing, Gladys Asiedu, Mary Ellen Young, Ebenezer Erefah, Folakemi Odedina, Roxana Dronca, Kimlin Ashing, Solomon Rotimi, Che Ngufor, Arnold Merriweather, Jennifer Crook, Manisha Salinas, Parisa Fathi, Sha’Reff Rashad, John McCall, Ayinde Yahaya. The iCCARE consortium for prostate cancer in Black men: Grounded theory study of the social determinant of health factors among African immigrant men diagnosed with prostate cancer [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 B050.

Abstract Background: Black men across the world continue to bear the burden of prostate cancer (PCa). Although several factors account for this, studies have demonstrated that the adaptive constitutive biological factors associated with African ancestry contribute to the risk of disease development, disease aggression, and poor disease outcomes in Black men. However, the limited inclusion of Blacks in cancer biology studies limits the understanding of the extent to which biology influence outcomes among Blacks. Furthermore, beyond White-Black dichotomous disparity, there exists an under-exploited within-group geographical and ancestral disparities in the burden, clinical presentation, and outcomes of PCa among Black men globally. Aside from urological and sexual problems, Black PCa survivors experience poor mental health, with a concomitant reduction in the quality of life and overall survival. Hence, improving the overall well-being of PCa survivors requires an understanding of the biological determinants of mental health among diverse groups of Black PCa survivors. Methods: Structured questionnaires are being used to access fatigue, pain, depressive symptoms, health-related quality of life, and PCa-specific symptoms burden among within a cohort of ethnically diverse Black PCa survivors in Africa. This is linked with the salivary biomarkers of inflammation, hypothalamic-pituitary-adrenal axis activity, and tryptophan-kynurenine pathway in our studies population. Results: Data from fifty PCa survivors across different African ethnic groups (including, Yoruba, Igbo, Hausa) will be presented. This study will measure biological variables (e.g, inflammatory markers, cortisol, tryptophan, kynurenine, and serotonin) and survivors self-reported (e.g. health-related quality of life and psychoneurological symptoms) measures to better examine the interconnectedness between cancer-associated biomarkers and poor mental health. Conclusion: This study will lay an essential foundation for understanding the extent to which cancer associated-biological determinants contribute to the poor mental health of PCa survivors, unravels the within-group disparities in the mental health of Black PCa survivors, establish the contribution of genetics to poor mental health in Black PCa survivors and provide the opportunity for pharmacogenomic intervention that will improve the quality of life. Citation Format: Solomon O. Rotimi, Folakemi Odedina, Roxana Dronca, Kimlin Ashing, Ernest Kaninjing, Che Ngufor, Arnold Merriweather, Jennifer Crook, Manisha Salinas, Fathi Parisa, Sha’Reff Rashad, John McCall, Ebenezer Erefah, Ayinde Yahaya. Investigating the biological determinants of poor mental health among ethnically diverse Black prostate cancer survivors: An iCCaRE consortium for prostate cancer in Black men project [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 A045.

Abstract Background: The prostate cancer (CaP) disparities experienced by Black men (BM) in the US is a microcosm of the burden of CaP seen in BM globally. The complexity of CaP disparities and the need for a unique approach to better understand and address a complex chronic disease, such as CaP, underscores the need for consortium research that is multilevel, collaborative, translational, and global. In response to this need, we brought together CaP survivors, advocates, scientists and clinicians to form the inclusive Cancer Care Research Equity (iCCaRE) for Black Men Consortium. Aim: Our overall goal is to optimize CaP diagnosis experiences, treatment and survivorship based on the Science of Survivorship (S.O.S). Our primary aim was to develop a consortium co-led by CaP scientists and survivors with multiple S.O.S research projects supported by research cores/services across multiple institutions. Methodology: The consortium was developed to comprise multiple individuals with complementary expertise and resources working collaboratively to achieve the common purpose of eliminating CaP disparities globally. Building on the expertise, resources, and relationships of collaborating CaP investigators, survivors and advocates, the iCCaRE Consortium was proposed to “advance health equity and reduce disparities in CaP” by studying the within-group differences among ethnically diverse BM and comparing US-born BM to their ancestral populations, including West African immigrant men in the US and indigenous West African men. Results: Through the Department of Defense Health Equity Research and Outcomes Improvement Consortium (HEROIC) Award, the iCCaRE Consortium was launched in 2022. There are five pilot projects (PPs), each co-led by a scientist PI and community PI: PP1 will plan and develop a Virtual Robot Assistant (ViRA) that will provide SDOH navigation services, psycho-oncology support and emotional support for BM newly diagnosed with CaP. PP2 will develop and analyze the impact of a patient-centered home cancer care system on health-related Quality of Life (HRQOL), access to healthcare, and PROs. PP3 will plan and develop a ViRA to improve HRQOL in Black CaP survivors. PP4 will employ the social determinants of migrant health framework to understand and address the needs of sub-Saharan African immigrant CaP survivors. PP5 will explore how biological factors induced by cancer cells contribute to poor mental health of CaP survivors. The PPs are supported by an Administrative Core, Translational Research & Clinical Intervention Service, Data Management and Analytics Services, Partnership Engagement Services, Pathology Resource & Biospecimen Core, Methodology and Measures Services and Digital Health & Human Services. Conclusion: The iCCaRE Consortium will “improve HRQOL to enhance outcomes and overall health and wellness for those impacted by CaP” by developing and implementing Artificial Intelligence interventions that address social determinants of health, psycho-oncology support and emotional support for newly diagnosed CaP patients. Citation Format: Folakemi Odedina, Roxana Dronca, Kimlin Ashing, Ernest Kaninjing, Solomon Rotimi, Che Ngufor, Arnold Merriweather, Jennifer Crook, Manisha Salinas, Fathi Parisa, Sha’Reff Rashad, John McCall, Ebenezer Erefah, Ayinde Yahaya. Addressing prostate cancer disparities through the Inclusive Cancer Care Research Equity (iCCaRE) for Black men consortium [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 A042.

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.

In this study, we used whole-exome sequencing of a cohort of 45 advanced-stage, treatment-naïve Nigerian (NG) primary prostate cancer tumors and 11 unmatched nontumor tissues to compare genomic mutations with African American (AA) and European American (EA) The Cancer Genome Atlas (TCGA) prostate cancer. NG samples were collected from six sites in central and southwest Nigeria. After whole-exome sequencing, samples were processed using GATK best practices. BRCA1 (100%), BARD1 (45%), BRCA2 (27%), and PMS2(18%) had germline alterations in at least two NG nontumor samples. Across 111 germline variants, the AA cohort reflected a pattern [BRCA1 (68%), BARD1 (34%), BRCA2 (28%), and PMS2 (16%)] similar to NG samples. Of the most frequently mutated genes, BRCA1 showed a statistically (P ≤ 0.05) higher germline mutation frequency in men of African ancestry (MAA) and increasing variant frequency with increased African ancestry. Disaggregating gene-level mutation frequencies by variants revealed both ancestry-linked and NG-specific germline variant patterns. Driven by rs799917 (T>C), BRCA1 showed an increasing mutation frequency as African ancestry increased. BRCA2_rs11571831 was present only in MAA, and BRCA2_rs766173 was elevated in NG men. A total of 133 somatic variants were present in 26 prostate cancer–associated genes within the NG tumor cohort. BRCA2 (27%), APC (20%), ATM (20%), BRCA1 (13%), DNAJC6 (13%), EGFR (13%), MAD1L1 (13%), MLH1 (11%), and PMS2 (11%) showed mutation frequencies >10%. Compared with TCGA cohorts, NG tumors showed statistically significant elevated frequencies of BRCA2, APC, and BRCA1. The NG cohort variant pattern shared similarities (cosign similarities ≥0.734) with Catalogue of Somatic Mutations in Cancer signatures 5 and 6, and mutated genes showed significant (q < 0.001) gene ontology (GO) and functional enrichment in mismatch repair and non-homologous repair deficiency pathways. Here, we showed that mutations in DNA damage response genes were higher in NG prostate cancer samples and that a portion of those mutations correlate with African ancestry. Moreover, we identified variants of unknown significance that may contribute to population-specific routes of tumorigenesis and treatment. These results present the most comprehensive characterization of the NG prostate cancer exome to date and highlight the need to increase diversity of study populations. Significance: MAA have higher rates of prostate cancer incidence and mortality, however, are severely underrepresented in genomic studies. This is the first study utilizing whole-exome sequencing in NG men to identify West African ancestry-linked variant patterns that impact DNA damage repair pathways.

Abstract 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. Citation Format: Jason A. White, Ernest Kaninjing, Kayode A. Adeniji, Paul Jibrin, John O. Obafunwa, Chidiebere N. Ogo, Mohammed Faruk, Solomon Rotimi, Ademola Popoola, Omolara A. Fatiregun, Olabode P. Oluwole, Balasubramanyam Karanam, Wei Tang, Stefan Ambs, Folake T. Odedina, Damali N. Martin, Clayton Yates. Tumor only analysis of whole exome sequencing from a multi-institutional Nigerian prostate cancer cohort reveals DNA repair genes associated with African ancestry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1507.