Determination of haptoglobin, hemoglobin genotypes and malaria incidence in Nigerian breast cancer patients

Breast cancer is the second leading cause of cancer morbidity and mortality globally. Cancer chemotherapy commonly result in hemolysis, which impacts patient overall health. There is a need to determine genetic factors associated with hemolysis in breast cancer patients. Haptoglobin (Hp), a polymorphic protein plays important role in hemoglobin clearance and disease predisposition, but has been reported to have no prognostic factor in breast cancer. However, understanding selection pressure that drives certain gene mutations in specific populations and how it confers protection or susceptibility to diseases is crucial. In Nigeria, breast cancer, malaria infection and sickle cell disease are prevalent and associated with hemolysis, but little is known of their association in breast cancer patients. This study aims to determine relationship between haptoglobin, hemoglobin genotypes and submicroscopic malaria co‐morbidity in clinically diagnosed breast cancer and healthy Nigerian women. DNA was extracted from blood using standard methods. Haptoglobin 2 and hemoglobin genotypes were detected by RFLP‐PCR, while Plasmodium falciparum infection was detected by primer specific amplification of plasmodium cytochrome oxidase III gene (cox III) in 75 clinically diagnosed breast cancer (BC) and 287 healthy women (control; HC). Proportions were determined and compared in the two groups and test of association was carried out with significance level set at P <0.05. In BC groups, 3 (4.1%) of 72 Hp 2‐2 phenotypes was detected compared to a significantly higher occurrence of 48 (16.7%) of 287 in HC group (p <0.05). Conversely, malaria infection was detected in 68 (94.4%) BC versus 255 (88.9%) in HC group. A similar proportion had Hp deletions (2 in BC and 8 in HC group). There was a low prevalence of hemoglobin S genotype in the entire population and relative risk for Hp 2‐2 polymorphism in hemoglobin genotypes was not significantly different. In conclusion, this study reports in breast cancer and healthy women an inverse correlation of haptoglobin (Hp2‐2) genotype with malaria incidence in southwest Nigeria. The results imply a possible protection against hemolysis and can play significant role in determining choice of cancer therapy for good patient treatment outcomes

Innovative Breast Cancer Awareness and Advocacy Campaign

Breast cancer is a major disease in Nigeria; in 2012, 27,304 new occurrences were diagnosed, and the number of mortalities was 13,960. Greater than 70% of patients present with advanced disease, which has a poor survival outcome. The mortality rates are high mainly because of a lack of awareness about breast health, screening guidelines, and treatment centers, and because of sociocultural barriers. In Nigeria, health care professionals remain the backbone for the provision of medical information to the public. This is a study of the innovative ways that breast health and cancer awareness were promoted across communities and institutions in Lagos State, Nigeria, in 2015. Several community awareness campaigns were carried out in the forms of health talks, breast cancer screenings, radio and television interviews, and campaigns on social media. Anomalies noticed during the screenings were promptly referred to appropriate hospitals for additional treatment. The campaign culminated in the #12KLLP, or 12,000 people light Lagos pink, which was a Guinness World Record attempt for the largest human awareness ribbon formed for breast cancer. There was a total reach of 28,774,812 people across platforms: 285,318 were on social media, 3,620 were in communities, 7,466,276 were on the website, 20 million were through media events, 12,000 were through publications, 7,598 were verified participants at the Guinness World Record, and approximately 1 million were through blogs. Eighty partnerships were made with various private and government institutions to facilitate different aspects of the campaign. The community members were able to learn about the need for early detection and awareness; volunteerism and corporate social responsibility were promoted among individuals and corporate institutions

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

Abstract D034: Patient and provider concordance and trust in providers among West African Immigrants: Findings from the CaPTC Familial Cohort Study

Background Healthcare disparities among racial and ethnic groups have been well documented across all aspects of clinical healthcare, and disparities in attainment of preventive services are particularly prevalent. African immigrants may be particularly susceptible to factors that contribute to healthcare disparities but little is known about this population. The purpose of this study was to assess patient-provider concordance and trust of health care providers among West African immigrants in the US. In addition, we explored the relationship between these variables and the prostate cancer (CaP) screening behavior of participants. Methods Data collection was part of a global study of prostate cancer in West African men. A study questionnaire was used to collect data from West African male immigrants in the US between the ages of 35 and 70 years. Survey scales for this study included country of birth, years since immigration, patient– provider concordance, trust of healthcare provider, attitude and cues towards CaP screening (PSA and DRE), and CaP screening history. Results There were 38 African immigrants from Cameroon, Nigeria, Sierra Leone, and Ghana. Participants’ average age was 46.2 years and they had spent an average of 13.9 years in the US. Most of the participants (over 60%) stated that they had no preference in regards to their provider race, ethnicity or gender. Over 70% indicated that their physician was of different ethnicity and race while 50% indicated that their physician was of a different gender. Furthermore, most respondents noted that they trusted their physicians with health decisions. However, 61% and 68% of participants did not complete PSA or DRE testing, respectively. Most stated that they did not discuss the advantages or disadvantages of prostate cancer screening with their physicians, noting they mostly received cues to getting tested from reading information, radio, and/or TV. Conclusion Although health disparities can be explained by socioeconomic status such as lack of insurance and various other observable impediments to accessing health care, others barriers persist. It is important to explore other contributing factors such as patient-physician relationships. This study suggests that patient-provider concordance may not be a priority. Emphasis should be placed on encouraging physician-initiated discussion on CaP screening. Unfortunately, current physician guidelines do not stress CaP screening and fail to account for the documented increased risk and early onset of CaP in Black Men

Examining Cancer Patients' Perceptions of the Impact of COVID-19 on Teleoncology: Findings From 15 Nigerian Outpatient Cancer Clinics

PURPOSETo examine cancer patients' perspectives on the impact of COVID-19 on teleoncology in Nigeria.METHODSData from a multicenter survey conducted at 15 outpatient clinics to 1,097 patients with cancer from April and July 2020 were analyzed. The study outcome was telemedicine, defined as patients who reported their routine follow-up visits were converted to virtual visits because of COVID-19 (coded yes/no). Covariates included patient age, ethnicity, marital status, income, cancer treatment, service disruption, and cancer diagnosis/type. Stata/SE.v.17 (StataCorp, College Station, TX) was used to perform chi-square and logistic regression analyses. P values ≤ .05 were considered statistically significant.RESULTSThe majority of the 1,097 patients with cancer were female (65.7%) and age 55 years and older (35.0%). Because of COVID-19, 12.6% of patients' routine follow-ups were converted to virtual visits. More patients who canceled/postponed surgery (17.7% v 7.5%; P ≤ .001), radiotherapy (16.9% v 5.3%; P ≤ .001), and chemotherapy (22.8% v 8.5%; P ≤ .001), injection chemotherapy (20.6% v 8.7%; P ≤ .001) and those who reported being seen less by their doctor/nurse (60.3% v 11.4%; P ≤ .001) reported more follow-up conversions to virtual visits. In multivariate analyses, patients seen less by their doctors/nurses were 14.3 times more likely to have their routine follow-ups converted to virtual visits than those who did not (odds ratio, 14.33; 95% CI, 8.36 to 24.58).CONCLUSIONCOVID-19 caused many patients with cancer in Nigeria to convert visits to a virtual format. These conversions were more common in patients whose surgery, radiotherapy, chemotherapy, and injection chemotherapy treatments were canceled or postponed. Our findings suggest how COVID-19 affects cancer treatment services and the importance of collecting teleoncological care data in Nigeria

Utility of formalin-fixed, paraffin-embedded prostate biospecimens from low-resource settings for use in next-generation sequencing studies in African-descent populations

# Background Men of African ancestry experience higher burden from prostate cancer compared to men of other ancestral backgrounds. Limitations in the availability of high-quality biospecimens hinder the inclusion of this population in genetic studies of prostate cancer. The use of formalin-fixed paraffin-embedded (FFPE) tissues represent a potential rich source of genetic material particularly in some international settings, where fresh frozen tissue is difficult to obtain. In this study, we investigate the feasibility of using FFPE biospecimens acquired from various international sites for utility in next-generation sequencing. # Methods A total of 976 FFPE blocks were collected between 2002 and 2017 from six international sites in Africa and the Caribbean representing three consortia: Prostate Cancer Transatlantic Consortium; African-Caribbean Cancer Consortium; and Men of African Descent and Carcinoma of the Prostate. Genomic DNA was checked for quality and quantity. Differences in mean quality control (QC) for pre-and-post pathology training were assessed using t-test. Pearson chi-square with trend analysis examined association between time-category and QC success status. Association of continuous DNA quality (Q129/Q41 ratio) and time of specimen collection was estimated with linear regression. Samples with a DNA quantity \>0.2µg and a Q129/Q41 ratio \>0.00225 were submitted for whole exome sequencing (WES). # Results There was a positive relative percentage change in DNA quantity from 2002 to 2017 for Jamaica, Kenya and Senegal. There was a decline in DNA quantity over the same time period for Nigeria. There was a statistically significant improvement in quality of samples from Kenya (*P*=0.032), Nigeria (*P*\<.001) and Senegal (*P*=0.043). There was a significant improvement in the collected DNA sample quality over time with an R^2^ of 0.12. # Conclusions FFPE samples from low-resource settings could potentially provide sufficient DNA for WES. Improvements in biospecimen collection processing and storage for research are needed in some of these settings