Over the past decade, genomic advancements have afforded tremendous opportunities in cancer research; including characterization of gene expression networks that distinguish tumor types, and the resolution of genomic structure that drives tumor growth and treatment outcomes. Despite these advances, disparities in cancer outcomes persist as does our paucity in data to understand the breadth of diversity in tumor traits across populations. Most of the data that defines our current understanding of cancer genetics was generated within the context of mainly European ancestry. This bias is partially due to geographic convenience of recruitment within the proximity of the institutions that generate these data elements. This type of systemic bias has perpetuated disparities of already marginalized racial minority populations, compared to their European race-group counterparts. However, international consortia have led to new insights and access, with strategic recruitment and study designs that harness population genetic diversity. Germline genomic investigations have uncovered ancestral susceptibilities that are either due to prevalence of ancestry-specific risk alleles or ancestrally/evolutionarily conserved modifiers of molecular pathways that prime development of certain tumor subtypes. Tumor/somatic genomics have repeatedly uncovered gene signatures that reflect thematic differences in tumor immune microenvironment as well as copy number variations, which are more recently being investigated with high-resolution technologies in imaging and genomic architecture, linked to genetic ancestry. As we turn our lens to the genomic context of population diversity, we are realizing novel opportunities to develop transformative precision medicine applications. Specifically, for this plenary presentation, we will highlight the transition of GWAS studies to functionalize genetic ancestry differences, enhanced with inclusion of ancestral populations, as opposed to the traditional filtration of these features. We will overview the newest concepts of complex germline and somatic architecture in the context of disparities and how these are determining the mysterious function of genomic associations identified as population-private risk across multiple ethnicities; including Asian, Latin American and African ancestry clades. We will demonstrate the utility of Whole Genome Sequencing in the clinical genetics space to mitigate disparities by characterizing the pathological features (Genomic Phenotypes) of the insidious Variables of Unknown Significance (VUS) and how these findings can fast-track minority access to alternative treatments. These data will ultimately improve our interpretations of overall cancer risk and risk of recurrence test results and recalibrate risk models. Lastly, we give a call to action that resounds the importance of including not only the genetic history (ancestry) but also the social history (self-reported race) of cancer patients and how this multidisciplinary approach will unlock our understanding of the drivers of aggressive tumor biology and be a catalyst for implementation of customized prevention and survivorship interventions. Only with the “Power of Inclusion” can we hope to traverse the breadth of disparities and make leaps of progress in cancer research and treatment.

Citation Format: Melissa B. Davis. Ancestry and cancer disparities: Genomic sequencing in diverse populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr PL01-03.