Melissa Davis, PhD, discusses the ongoing research of genomic sequencing in diverse populations, including cancer disparities and ancestries. These data were presented at the 2021 AACR Annual Meeting. 

Transcript

My name is Melissa Davis. I am an Assistant Professor of Cell and Developmental Biology in the Department of Surgery at Weill Cornell. I also serve as the Scientific Director for the International Center for the Study of Breast Cancer Subtypes, and I am a member of the Englander Institute for Precision Medicine.

I am going to give you a brief overview of the opening plenary, "Genomic sequencing in diverse populations, including disparities and ancestries," and I gave an overview of the Polyethnic-1000 Project.

The research that I presented is ongoing. Actually, it was established, I would say, almost 10 years ago, the founding observations that led to the hypothesis, which is that part of what we see in disparities of cancer outcomes is driven by biological determinants that could be due to shared genetic ancestry.

One of the themes that I heavily introduced and repeated was this concept of oncologic anthropology.

That concept was born from the fact that, typically, when we are looking for genetic drivers of cancer risk or even tumor phenotypes, we would look within family groups to show the transmission of the disease correlated with genetic mutations. For instance, the most common BRCA alleles were identified by looking at large pedigrees of breast cancer transmission through families.

However, in certain minority groups, such as African Americans, in the United States, the family health history is very incomplete, as is the relatedness of individuals through a pedigree analysis that would extend beyond three generations, for instance, in contemporary families.

We have this disconnection of information, though in the whole population, we do see a larger percentage of certain phenotypes of breast and even prostate cancer and other types of cancers more prevalent in this population.

In the concept of global oncology, and using global epidemiological evidence, we were seeing that triple-negative breast cancer was more prevalent in every nation where we could discern triple-negative status, and where we could discern the component of the population that was of African descent.

That is the first clue that there could be a shared genetic driver across the African diaspora that is giving a predisposition to triple-negative breast cancer. With that, we started to investigate contemporary African populations. We saw, for instance, that West African populations had a higher incidence of triple-negative breast cancer.

Then, in African Americans, we measured genetic ancestry and saw that, of those individuals who had the highest amount of West African ancestry, because African Americans, of course, are admixed with European primarily, but then also Native and Asian populations as well, the component of the admixed populations that had the highest amount of West African ancestry also were the ones who were more likely to have triple-negative breast cancer, as opposed to other types of breast cancer.

Then we started drilling down into what percentage of the population harbors a genetic driver. It is like a population-level transmission of a molecular marker that corresponds with a tumor phenotype.

Then the real-world applications of the findings, how we first translate this in clinic, how will we first translate this into clinic, and how it will become transformative, one of the examples I gave was that, as we identify these genetic drivers that were not identified in larger genome-wide association studies, we can start reinforming genetic risk models, mutation panels, even diagnostic tests.

Right now, most of these clinical applications are primarily derived from the European diaspora. Those GWA studies were primarily individuals of European descent. Now, we are starting to appreciate that genetic diversity also gives us a more in-depth look at tumor basic biology.

Expanding on this research, one of the things we are doing is, for instance, in all aspects of tumor biology, tumor immune landscape, metabolics, microbiomes, drug screening, treatment paradigms, now, we are really reinforming ourselves by using diverse populations, making targeted enrollment recruitment paradigms so that we can gain better access to diversity around all of these research studies to reinform ourselves on adversity and whether or not we have fully understood the tumor biology and/or treatment responses across the broad population of breast cancer patients.