Era of Hope 2011 Investigator Vignette

Title: A Genome-Wide Breast Cancer Scan in African Americans

Investigator: Chris A. Haiman, ScD; University of Southern California

I have an Era of Hope Scholar Award that--to conduct a genome-wide association study of breast cancer in African American women, to identify-we hope-markers of risk that may be particularly important in this population and help us to better understand the greater incidence of estrogen receptor negative breast cancer, which is associated to poor prognosis in this population.

We've realized in looking at the genetic markers that have been identified in populations of European ancestry and I'm talking about genetic markers to breast cancer, when we evaluate those in African American women, only roughly half of them appear to serve as adequate markers of risk, which is telling us that we need to do a better job of really understanding or characterizing risk within these known regions where there does appear to be a marker susceptibility in this population. And some of our work using the million or two million SNPS in our stage one sample is allowing us to go and crucially and comprehensively interrogate each of these regions to try to extract the information about risk.

We are currently analyzing more than 2,000,000 genotypes that have been investigated in about 3,000 African American breast cancer cases in just over 2,700 controls. Some of our initial discoveries in this first stage have been taken forward to additional replication studies in populations of African ancestry as well as in European populations. And we're hoping to get those data relatively soon so we can analyze them to see if we have any novel discoveries.

Despite the large size of this study, which is considerably large compared to other genome-wide association studies it's really going to be not large enough.

I think what we've realized is the effects of the risk alleles are relatively low. In order to detect them, we need very, very large samples and I think it's understood now in the research community that no single study is going to be able to act alone to identify them.

I had to reach out to epidemiologists throughout the United States and convince them that in order to make novel discoveries in this population we're going to be needing to work together. And so this first stage includes about 10 different investigators from across the United States that have been willing and eager to pool their data and samples from their respective studies to make this a very successful project.

Once you identify a marker of risk, the next step is to better characterize its association with risk and you have to understand its biology. And we have a number of additional applications under review that include molecular biologists, tumor biologists, and clinicians to help us draw the link between the association with risk and the underlying biology. And I think that's really where multidisciplinary science is going to play an important role in translating the information that comes from genome-wide association studies into information that can be used clinically or with respect to understanding the true biology.

My research doesn't focus on trying to find a cure. My research focuses on trying to prevent the disease and to understand who is at significantly higher risk of developing the disease so that those subjects could be the focus of more aggressive or more intensive measures of screening or try to understand the etiology of the disease so we can identify preventive strategies, so women don't develop the disease in the future. And I think one of the areas that is going to be at the forefront of this is going to be the genetic medicine. Within a few years, we're going to be sequencing everybody's genome and it's going to be reasonable and practical; it's going to be feasible to do and I think that's an area where we're going to make a dramatic impact in truly identifying that 10 to 15 or 20% of the population who are a significantly greater risk of developing breast cancer. So that will be the group that we'll need to target and try to reduce the morbidity and mortality of the disease.