Purpose: A higher Neutrophil-Lymphocyte ratio (NLR) has been asso- ciated with poor prognosis in many diseases. Most Africans are neutro-penic due to the duffy antigen null status. The duffy antigen null status however, has been associated with a higher risk of organ damage in peo-ple living with sickle cell disease (SCD). We therefore sought to deter- mine the effect of the proportion of these blood cells to one another on SCD prognosis in Nigeria. Materials and methods: One hundred and thirty (130) sickle cell disease patients in steady state and 117 healthy age- and sex-matched controls were recruited from a tertiary institution in Nigeria. All the participants gave informed consents and blood samples were taken for Full Blood Count and phenotyping by High Performance Liquid Chromatography. Demographic and clinical details were obtained by questionnaire admin- istration. Neutrophils make up over 90% of granulocytes, hence the granulocyte-lymphocyte ratio was determined from the available abso- lute counts of granulocytes and lymphocytes. A subset of 110 patients who were not on hydroxyurea was used for the analysis. The patients were divided into 3 age groups (< 7years, 8 – 17years and >17years). Purpose: Defective spleen function (hyposplenism) affects subjects with sickle cell disease (SCD) and is associated with complications. Red blood cell (RBC)-related markers are very accurate to assess spleen function. Vacuole-containing RBC (pocked RBC) are observed in high propor-tions (10 to 70%) of hyposplenic subjects whereas they do not exceed 5% of RBC in healthy subjects. Vacuoles in pocked RBC are considered by many as remnants of erythropoiesis-related processes. Materials and methods: Patients with SCD who benefit from an exchange transfusion program, have not only their own HbSS RBC but also transfused HbAA RBC in circulation. In vitro sickling “Emmel test” discriminates HbSS RBC, that sickle, from HbAA RBC, that do not. We perfused a mixture of HbSS RBC and HbAA RBC (from exchange transfusion left-overs) into human spleens ex-vivo. We then analyzed spleen sections and quantified vacuoles in RBC containing hemoglobin polymers or not. Results: Using Emmel test, we observed vacuoles in HbSS RBC but also in transfused HbAA RBC. Pocked HbAA RBC were more frequent in transfused SCD patients than in healthy subjects (25.1±4.41% vs. 2.8±2.1%).Into human spleen ex-vivo, we observed a high rate of vacuoles in either polymerized and non-polymerized RBC (29.8±3.7% vs. 17.9±5.8%). In our experimental set-up, HbAA RBC is deducted as the absence of polymerization. Conclusion: Taken together, these results strongly suggest that vacuoles are created de novo in transfused HbAA RBC.Counting vacuoles in RBC labeled with anti-HbS and anti-HbA antibody is ongoing to validate these observations. When the spleen is dysfunctional, these pocked RBC stay in circulation hence their of seventy-four twenty-four Purpose: A child’s growth reflects it nutritional and pubertal status and it is proven that nutrition is a factor affecting pubertal development. Sickle cell patients often have slowed growth and delayed pubertal develop- ment. This work aims to assess the nutritional and/or pubertal profile in children with sickle cell diseases (SS) admitted at the CEMECO center. methods: This was a cross-sectional study and study par-ticipant years were randomly selected from the health center database having about cases and enrolled in the study.The participants were divides into two groups based on the electrophoresis of hemoglobin: Sickle cell disease including 103 cases of SS (homozygote) and 18 cases of SC, S, β -Thalassemia and SE (heterozygous). While the group of non-sickle cell participants includes 87 (AA and AS) Results: We included 208 children among them121 sickle cell disease patients and 87 non sickle cell diseasechildren. with a sex ratio M/F was about1.02. The meanage of sickle cell patients was 8.7±4.4 years while that of non-sickle cell patients was 9.5 ± years. The family income

Abstract Objectives: Paucity of data on populations of African Ancestry in clinical trials continues to limit our ability to design and implement innovative solutions to narrow the breast cancer survival gap amongst Africans, African Americans, and European Americans. We have developed a cross-continent research infrastructure to examine the spectrum of genomic alterations in breast tumors from West Africa and subsequently, to compare them to tumors from African American women and women of European Ancestry in The Cancer Genome Atlas (TCGA) database. Methods: Consecutive women with breast cancer presenting for treatment at the University College Hospital, Ibadan and at Lagos State University Teaching Hospital, Lagos, Nigeria gave informed consent and were recruited to the West African Breast Cancer Study (WABCS) between 2013-2016. Tumor-normal pairs were subjected to exome and/or high-depth (90x) genome sequencing. High confidence somatic mutations (substitutions, insertions/deletions and structural variants) were obtained by using multiple variant callers. Furthermore, 1,089 exomic and 80 genomic breast tumor-normal pairs from TCGA were harmonized with WABCS samples, resulting in a cohort of 147 West Africans (147 exome; 40 genome), 154 African Americans (154 exome; 31 genome), and 776 Caucasians (776 exome; 43 genome). Results: Across the exomes, genes commonly altered in breast cancer in TCGA are also altered in women of African ancestry, but the mutational spectrum is quite different, demonstrating overrepresentation of tumors with aggressive phenotypes. Overall, TP53 (65%), ERBB2 (27%), and GATA3 (17%) showed statistically significant higher alteration frequencies in West Africans and African Americans. In contrast, PIK3CA (24%) was less frequently mutated. Of note, GATA3 mutation was statistically significantly more frequent in Nigerians (39%) and African Americans (16.7%) compared to Caucasians (10.5%), in ER-positive cancers. Analysis on Structural Variants (SV), on the other hand, has shown that the genome-wide SV counts among three populations are comparable in ER-negative cancers, while Nigerians have significantly more SV counts compared to African Americans (P=0.0013) or European Americans (P=2.9x10-5) in ER-positive cancers. Similarly, genome-wide substitution patterns in ER+ and ER- cancers varied widely by race/ethnicity. In ER- cases, West Africans carried the highest proportion of canonical APOBEC-associated substitutions, particularly C>T transitions. Conversely, European Americans with ER+ disease showed a higher proportion of C>T than both West Africans (Welch t-test P = 0.044) and African Americans (Welch t-test P = 0.011). Mutation signature analyses highlighted multiple APOBEC signatures, with notable contribution differences across ancestry and ER status. A signature likely corresponding to DNA damage repair correlated with the proportion of genetic ancestry, being most prevalent in European Americans and least common in Nigerians, particularly in ER-negative cancers, with African Americans showing a degree of this signature's contribution in between the two populations (linear model adjusted for age, P=1.0x10-10). Conclusions: Overall, our data suggests mutation spectra differences in across race/ethnicity and geography. Identification of molecular characteristics such as higher rates of HER2 enriched tumors and higher rates of GATA3 mutations in ER positive tumors are beginning to reveal the genomic basis of race-associated phenotypes and outcomes in breast cancer. Population differences in frequency and spectrum of mutations should now inform the design of innovative clinical trials that improve health equity and accelerate Precision Oncology care in diverse populations. Citation Format: Olopade OI, Pitt JJ, Riester M, Odetunde A, Yoshimatsu T, Labrot E, Ademola A, Sanni A, Okedere B, Mahan S, Nwosu I, Leary R, Ajani M, Johnson RS, Sveen E, Zheng Y, Wang S, Fitzgerald DJ, Grundstad J, Tuteja J, Clayton W, Khramtsova G, Oludara M, Omodele F, Benson O, Adeoye A, Morhason-Bello O, Ogundiran T, Babalola C, Popoola A, Morrissey M, Chen L, Huo D, Falusi A, Winckler W, Obafunwa J, Papoutsakis D, Ojengbede O, White KP, Ibrahim N, Oluwasola O, Barretina J. Comparative analysis of the genomic landscape of breast cancers from women of African and European ancestry [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD8-05.

Abstract Objectives: Of all ethnic/racial groups, age-standardized mortality rate from breast cancer is highest for African American women in the US for reasons that remain understudied. The paucity of genomic studies of breast tumors across the African Diaspora further restricts our understanding of the biology of breast cancer in underserved populations. To gain a better understanding of the genomic landscape of breast cancer in women of African Ancestry, we have developed a cross continent translational research infrastructure to examine the spectrum of genetic alterations in breast tumors from West Africa compared to the spectrum of alterations observed in tumors from African-American and other women who are predominantly white in The Cancer Genome Atlas (TCGA) dataset. Methods: Peripheral blood and breast cancer biopsy tissues were collected from 214 patients enrolled in the West Africa Breast Cancer Study (WABCS) at the University of Ibadan/University College Hospital (UI/UCH) and at Lagos State University Teaching Hospital (LASUTH). Blood DNA as well as breast cancer tissue DNA and RNA were extracted at the Novartis Institutes for Biomedical Research (NIBR), UI/UCH, and LASUTH using a modified protocol of PAXgene Tissue DNA and RNA extraction method. Whole-exome (WES) and transcriptome (RNA-seq) sequencing were performed on the Illumina HiSeq2000 platform at NIBR. Single Nucleotide Variants (SNVs) and insertions/deletions (indels) were called using MuTect and Pindel, while Copy Number Alterations (CNAs) were called using an in-house implementation of the ABSOLUTE method. Observed mutations were compared against those reported in the TCGA dataset. ER, PR and HER2 status were determined by immunohistochemistry (IHC) at UI/UCH, LASUTH and UChicago. Results: WES data for 95 tumors have been analyzed thus far. Genes commonly mutated in breast cancer in TCGA are also mutated in WABCS but the mutational spectrum is vastly different. TP53 (64%), MYC (31%), and GATA3 (26%), showed significantly higher alteration frequencies in WABCS and African Americans. In contrast, PIK3CA (20%), CDH1 (2%), and MAP3K1 (2%) were less frequently mutated in women of African ancestry. In addition to the high proportion with TP53 mutations, the proportion with HER2 positive subtype of 42.1% and triple-negative subtype of 37.9% suggest that tumors with the most aggressive features are overrepresented in breast cancer patients in West Africa. Conclusions: In the first study of its kind, high throughput genomic analysis of the largest cohort of women of African ancestry has uncovered alterations in cancer genes, some of which may be amenable to treatment with targeted therapies. Furthermore, we provide evidence that population differences in frequency and spectrum of mutations should drive the design and deployment of precision medicine initiatives. Only then can we develop innovative interventions to reduce the unacceptably high rates of mortality from breast cancer in underserved and under resourced populations. Citation Format: Olopade OI, Odetunde A, Riester M, Yoshimatsu T, Labrot E, Ademola A, Sanni A, Okedere B, Mahan S, Nwosu I, Leary R, Ajani M, Johnson RS, Sveen E, Zheng Y, Clayton W, Khramtsova G, Oludara M, Omodele F, Benson O, Adeoye A, Morhason-Bello O, Ogundiran T, Babalola C, Popoola A, Morrissey M, Huo D, Falusi A, Winckler W, Obafunwa J, Papoutsakis D, Ojengbede O, Ibrahim N, Oluwasola O, Barretina J. Genomic landscape of breast cancers from women of African ancestry across the diaspora. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-03-17.

Background: Access to clean energy is a basic requirement in developed countries. Yet, over 3 billion people worldwide, mostly women and children in developing countries depend on biomass fuel for their cooking and energy needs. The smoke emanating from cooking with biomass causes indoor air pollution which pose significant health risks. Methods: A community-based pilot study was conducted in Southwest Nigeria to determine the prevalence of respiratory symptoms among women and children in homes that use biomass fuel for cooking. A total of 102 households with at least a child were recruited for this study. The mothers in each household were interviewed using a questionnaire developed to understand their cooking habits, knowledge of health risks related to cooking indoors with firewood and to estimate the prevalence of respiratory symptoms. Descriptive statistics was used to estimate household biomass fuel use, respiratory and associated symptoms. : Results The mean age of the mothers and children surveyed were 40±11.54 and 14±3.47 years respectively. Almost 63% cook inside their houses in poorly ventilated kitchens or hallways. Additionally, more than two-thirds (84.3%) of the mothers have their children with them during cooking with majority (74.6%) exposed to smoke for at least 4 hours/day. Common symptoms experienced during cooking are shown in Table 1. Among the various symptoms experienced, burning sensation in the eyes was the most common in mothers and children. Respiratory complaints were also very common, although only 4.8% of mothers and 2.9% of children reported being diagnosed with asthma. Frequent headaches was also reported in 40% of mothers and in almost 25% of children. Table 1: Firewood Smoke Associated Symptoms in Exposed Women and Children Symptoms Mothers (%) Children (%) Burning eyes 81.4 58.8 Headaches 40.0 23.8 Runny nose 37.1 36.2 Wheezing 22.5 16.7 Chest tightness 16.2 11.2 Dry cough 15.7 21 Difficulty breathing 13.7 17.6 Dizzines 10.5 3.8