West Africa Breast Cancer Study (WABCS)

Differences in breast cancer incidence and mortality rates between North American Caucasian and African American women are well-described and transcend socioeconomic issues. Black women are diagnosed with breast cancer at a younger median age; have more clinically aggressive disease and stage-for-stage; and have higher mortality rates than age-matched Caucasian women. Black women in West Africa, the origin of the slave trade in the US in the 19th century and thus the founder population for most African Americans, have even higher rates of early-onset, poor-prognosis breast cancer than African American women. Racial difference in the distribution of intrinsic molecular subtypes has been well characterized in the US and throughout the African Diaspora as well. Despite the large efforts on characterizing racial/ethnic differences, however, the reasons women of African ancestry are disproportionately affected by breast cancer incidence and mortality remain poorly understood - largely due to paucity of data on inherent genomic differences that contribute to the disparities in incidence and progression of breast cancer across populations. West Africa Breast Cancer Study (WABCS) is an initiative that aims to comprehensively understand the genetic architecture of breast cancer in West Africans, the founder population of a large proportion of black women in the United States. The objective of the study was to provide a better understanding of the molecular genetic factors that influence prognosis in Nigerian breast cancer patients, and determine which of these alterations may be amenable to available therapy. To that end, we examined the molecular features of breast cancers of indigenous African women using a combination of whole-genome, whole-exome, and transcriptome sequencing (WGS, WES, and RNA-seq) on 194 tumors from Nigerian patients. The goal of this project was to obtain answers to two related research questions using an unscreened population without genetic admixture in Nigeria: 1) why are women of African ancestry more likely to develop aggressive young onset breast cancer? 2) What are the associated genomic and non-genomic risk factors? We hypothesize that the genomic determinants of breast cancer molecular subtypes in women of African ancestry are also molecular drivers of tumor progression and represent targets for interventions to improve clinical outcomes and close the mortality gap. By identifying causal links between genetic variants that promote aggressive tumor progression in Nigerian women in comparison to women from different population found in TCGA and ICGC, the present dataset will have significant public health impact on millions of women in the African Diaspora. The potential to identify novel pathways for interventions to reduce the increasing mortality gap between women of African and European ancestry is huge]]> Case ascertainment: Tumors from consecutive patients with breast cancer recruited between February 2013 and September 2015 at the University College Hospital (UCH) in Ibadan, and Lagos State University Teaching Hospital (LASUTH) in Lagos, Nigeria, were used for sequencing. Patients with breast cancer aged 18 and above, who were clinically diagnosed in the Department of Surgery of UCH or Department of Surgery of LASUTH were eligible for this study. All consecutive eligible cases were approached. After obtaining informed consent, patients were interviewed and completed epidemiologic questionnaires administered by a trained nurse. Diagnostic biopsies as well as blood and additional biopsy samples for subsequent experiments were collected during recruitment. UCH is the premier university teaching hospital in Nigeria, and offers tertiary level care to Oyo State (population of 5.6 million) and parts of the neighboring three states (Osun, Ogun, and Kwara states, with a combined population of 9.4 million). LASUTH is a state-run tertiary health facility that serves over 10 million people of Lagos metropolis. Both hospitals are referral centers for other hospitals in the region, where primary health centers and practicing doctors in the community refer patients to UCH and LASUTH for specialist care. Based on referral patterns, the majority of the cases of breast cancer diagnosed in the region would probably be seen at the UCH and a significant majority at LASUTH. Large proportion of patients present with advanced, non-resectable forms of the disease. Control ascertainment: The Nigerian Breast Cancer Study has been in the field since 1998. A population-based control recruitment strategy was used. A stable, socio-economically diverse community adjoining the UCH was randomly selected by ballot from a list of all the communities in the area. It is our belief that if anyone in any of these communities were to develop breast cancer, the person will attend the Oncology Clinics at UCH. A census register of the people living in the community was obtained and a meeting was arranged with the Head and Elders of the community, at which the purpose of the study was explained to them. After they consented, meetings were held in the local gathering places at which the purpose of the research was explained to members of the community. Names were then randomly selected from the community register and the people were invited to visit a clinic set up in the community for the study. Inclusion criteria for the controls were: females, age above 18 years, absence of any type of cancer or history of cancer at recruitment, predominant urban residence for most of their lives, and ability to give informed consent. After explaining the project to the potential participant, a complete physical examination was done. A trained nurse then interviewed the participants, measured their height and weight and completed the questionnaires.]]> WABCS was embedded within the larger Nigerian Breast Cancer Study (NBCS), which is a case-control genetic epidemiological study of breast cancer started in Ibadan, Nigeria through a collaboration between the University of Chicago and the University of Ibadan. The feasibilty phase of the study took place between 1998 and 2001 and was funded by the US Department of Defense Breast Cancer program. Phase 1 was funded with an R01 from the NCI between 2002 and 2010, and Phase II was funded through 4-Way partnership with Novartis Biomedical Research Institute and funding from Susan G Komen Scholar and Breast Cancer Research Foundation between 2011 and 2018. Following the 1st International Workshop on Breast and Cervical Cancer held in Lagos in 2004, we established a breast cancer laboratory within the Institute for Medical Research and Training at the University of Ibadan College of Medicine, to provide core research support and clinical services to all Nigerian medical institutions. This laboratory serves as central repository for our investigations. Staff were trained on best practice for tissue preparation and processing of FFPE tissues according to maintain high quality and integrity of the biospecimens. In 2013, the study protocol was updated to prepare for new study methods involving high-throughput massively parallel sequencing approaches. The Standard Operating Procedures were revised after studying the best practices in the field including TCGA to improve efficiency of patient recruitment and sample collection quality. The study was also expanded to include a new site in Lagos, Nigeria. Samples from the Nigerian Breast Cancer Study was used to conduct a Genome Wide Association Study (GWAS) of 1,973 cases and 2,283 controls, all of African ancestry. In 2012, The Root GWAS dataset was released to dbGaP for community access (accession phs000383.v1.p1).]]>