Kaninjing, Ernest

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: 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: Vitamin C has long been recognized for its plethora of immune system and anti-inflammatory properties. Various cancers have been identified to have similarities in epigenetic inflammatory components. Because rates of prostate cancer have exhibited significant disparities in Black men with increased incidence and mortality, an examination of the intersection of diet, inflammation, and cancer and chronic disease diagnoses necessitates researchers to consider vitamin C. This study utilized data collected from the Prostate Cancer Transatlantic Consortium (CaPTC) Familial Cohort Study, an ongoing longitudinal cohort study initiated in 2017 which explores risk factors of prostate cancer among African Black men in Nigeria, Cameroon, and the United States (U.S.). Aim: The aim of this study was to examine the consumption habits of vitamin C-rich foods in African Black men and determine if dietary patterns influenced risk of cancer diagnosis. Methodology: Descriptive analyses compared vitamin C-rich food consumption among the countries of Nigeria, Cameroon, and the U.S. Unadjusted logistic regression models were used to identify association of cancer diagnosis with consumption of vitamin C fruits and vegetables. Odds ratios and 95% confidence intervals were estimated. Results: From 803 unique participants included in this study, most resided in Nigeria (82.6%), were married (92.9%) with a median age of 50.7 years. Chi square tests revealed significant differences in dietary consumption of vitamin C-rich fruits and vegetables among the three countries. Men in Nigeria presented with the highest weekly fruit consumption (p < 0.001). Men in the U.S. exhibited the greatest weekly vegetable consumption (p < 0.001), while men in Cameroon showed the least weekly consumption of both fruits and vegetable (p < 0.001). Fourteen Cameroon and zero U.S. men reported a cancer diagnosis. Logistic regression models were significant only for Nigeria where age (p < 0.001), leafy vegetable (0.04), berries (p = 0.05), and citrus fruit consumption (p = 0.04) were identified to be significant predictors of increased risk of cancer diagnoses. Conclusion: Regular consumption of vitamin C rich foods assists with reduction of inflammatory components that may contribute to cancer genesis. Dietary consumption patterns of vitamin C rich fruits and vegetables show significant disparities in Nigeria, Cameroon and the U.S. with men in Cameroon reporting the least weekly consumption of both vitamin C-rich fruits and vegetables. Future investigation into revisiting these associations as well as including an assessment of access to quality nutrition in both cost and availability should be explored, as regular consumption of leafy vegetables, berries, and citrus fruit were found to significantly decrease risk of cancer diagnosis in this study. Citation Format: Jennifer M. Crook, Emeka Iweala, Ademola Popoola, Paul Jibrin, Mohammed Faruk, Anthonia Sowumi, Omolara Fatiregun, Nkegoum Blaise, Catherine Oladoyinbo, Ifeoma Okoye, Abdulkadir Ayo Salako, Abidemi Omonisi, Iya Eze Bassey, Kayode Adeniji, Nggada Haruna Asura, Ernest Kaninjing, Oluwole Kukoyi, Parisa Fathi, Ruth Enuka, Oluwaseyi Toye, CaPTC Investigators, Folakemi Odedina. Vitamin C prediction of cancer diagnosis in men of African ancestry in Nigeria, Cameroon, and the United States: An analysis of the CaPTC prostate cancer study [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 C068.

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.