Genome-Wide Association Study of Breast Cancer in the African Diaspora - the ROOT study

The paucity of data on the genetic epidemiology of breast cancer for racial/ethnic groups other than those of European ancestry hinders the development of innovative interventions to reduce health disparities. Women in the African Diaspora experience a disproportionate burden of pre-menopausal breast cancer in comparison to all other races for reasons that remain unknown and understudied. This higher proportion of early-onset breast cancer might suggest a stronger genetic component in these populations. Genome-wide association studies (GWAS) have revealed several genetic loci that confer risk of breast cancer. Because all GWAS started the discovery stage in women of European ancestry and replicated mainly in women of European ancestry, we propose a novel approach for a GWAS in indigenous African women to identify alleles associated with breast cancer risk which will then be replicated in other populations. This innovative design builds on our current understanding of the etiologic heterogeneity in breast cancer and the distribution of breast cancer molecular subtypes which differ between women of African ancestry and women of European ancestry. The major objective of the proposed studies is to get to the "root" causes of breast cancer by identifying breast cancer risk alleles in a pooled sample of women of African ancestry and to replicate our findings in other populations.

To achieve this objective, we conducted a case control study of breast cancer in women of African ancestry, including Africans living in Nigeria, African Americans and African Barbadians. We will genotype ~3800 individuals using the Illumina HumanOmni2.5-Quad platform. We will conduct both standard and novel genetic analyses of the data to map genes associated with breast cancer susceptibility, verify genotyping and carry out fine-mapping studies in genes or regions showing association with breast cancer risk, and replicate in other African American and non-African American populations. By pooling unique resources from studies throughout the African Diaspora, this study has the potential to identify risk alleles in several genes that contribute to increased breast cancer risk and may have implications for early detection, prognosis and treatment of breast cancer in ALL women. This should ultimately lead to improved outcomes for those who suffer a disproportionate burden of early-onset breast cancer.

• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 3766
• Subject Sample Telemetry Report (SSTR)

• BioProject
• BioSample
• MeSH

Women of African descent, 18 years old and older.

• Primary Phenotype: Breast Neoplasms

• Principal Investigator
  • Olufunmilyao I. Olopade. University of Chicago, Chicago, IL, USA.
• Funding Source
  • R01 CA142996. National Institutes of Health, Bethesda, MD, USA.
• Genotyping Center
  • Center for Inherited Disease Research (CIDR). Johns Hopkins University, Baltimore, MD, USA.
• Genotyping Quality Control
  • Genetics Coordinating Center. Dept of Biostatistics, University of Washington, WA, USA.
• Funding Source for Genotyping and Quality Control
  • HHSN268201100011I. National Institutes of Health, Bethesda, MD, USA.
  • HHSN268200782096C. National Institutes of Health, Bethesda, MD, USA.