Precision medicine research in diverse populations

Written by Erin Linnenbringer, PhD, MS, assistant professor in the Department of Surgery, School of Medicine

At the time of publishing, professor Linnenbringer was an instructor in the Department of Surgery

Essential to Meeting the Goal of Reaching the Right Patient With the Right Treatment at the Right Time

Many Americans have probably heard the term “precision medicine,” and have hoped that it may have a positive impact on their health or the health of a loved one. But what does it really mean? Does the hype live up to the current reality? Will this new approach help reduce heath disparities across populations, or make them even worse?

The term precision medicine gained traction as part of a 2011 National Research Council report summarizing the need to incorporate genetic, environmental, and social factors to create a more comprehensive approach for understanding, treating, and ultimately preventing disease. Following the 2015 State of the Union Address, the Precision Medicine Initiative was launched in an effort to build the knowledge and infrastructure needed to reach “the right patient with the right treatment at the right time.”

This lofty goal is starting to be realized. Most of the precision medicine success stories to date have been in the treatment of certain types of cancer. Physicians may order genetic testing on tumor cells to better predict which patients will benefit from various treatment options, such as radiation before, after, or in place of surgery. In some cases, physicians may even be able use the genetic test results to identify a targeted therapy that disrupts the growth of the tumor cells, or causes the tumor cells to die.

While tremendous progress has been made in developing precision medicine approaches, the gains are not uniform across all diseases, or even all types of cancer.

For example, several FDA-approved targeted therapies are currently used to treat advanced non-small cell lung cancer (NSCLC). However, only one-third to one-half of NSCLC tumors have a genetic mutation that is targeted by one of those therapies. The remaining patients who do not have a targetable mutation within their tumor are unlikely to benefit from the therapy.

Precision medicine approaches are currently limited by not only our understanding of complex genetic and biological processes, but also by the scope of our existing data. As of 2016, 80% of the participants in genome-wide association studies (GWAS) worldwide were of European decent, whereas approximately 7% of the global population fits this definition. This lack of diversity limits the development of precision medicine in several important ways. First, GWAS have been a critical first step in identifying genetic changes associated with common diseases and cancers for over a decade. These genetic changes are often subtle, in that each genetic change typically makes a small contribution to an individual’s overall risk of a common disease. Moreover, the genetic changes identified through GWAS usually reside within the 0.1% of the genome that differs from person to person. If we continue to look for those small genetic changes in only certain populations, we are likely to miss important genetic information from other groups, and potentially misinterpret the impact of the observed genetic changes. Therefore, increasing the diversity of GWAS and genomic sequencing studies is essential to improving precision medicine approaches and broadening their impact to non-European ancestry populations.

Including diverse populations in precision medicine research matters for non-genetic reasons as well. As described in the National Research Council’s report, identifying and incorporating environmental and social factors are also critical to developing precision medicine approaches. Within the United States alone, differences in exposure to health-impacting environmental factors, such as lead, are well-documented across geographically- and racially-defined populations. A growing body of research also points to social factors like isolation and discrimination as being both associated with poor health outcomes and more common within disadvantaged sociodemographic groups.

Many environmental and social factors impact health through non-genetic pathways, but in some cases, the disease risk associated with these exposures may greater among individuals with certain genetic backgrounds. In other cases, the exposure may be associated with turning on or turning off certain disease-associated genes within an individual.  Whether there is a genetic pathway or not, accounting for variation in living conditions across ZIP codes is just as important as examining variation across genetic codes. Developing approaches that incorporate known environmental and social health risk factors will help move precision medicine closer to its goal of providing the right patient with the right treatment at the right time.

But how do we overcome the current lack of diversity in foundational precision medicine research? Several major federally-funded initiatives are currently underway to address this very issue. The largest effort is the All of Us research program, a key component of the Precision Medicine Initiative. The All of Us research program will gather genetic, environmental, lifestyle, and biological data from at least one million Americans. To reach such a large population and insure its diversity, the All of Us program is partnering with regional medical centers across the country, including Federally Qualified Health Centers (FQHC). Many of FQHC patients are low income, racial or ethnic minorities, and/or rural residents – all populations that are underrepresented in most genetic and precision medicine studies completed to date. Interested individuals can also directly enroll in the study, which will open later this spring. In addition to the All of Us research program, the National Human Genome Research Institute has recently reviewed its efforts and outlined additional actions that both researchers and funding agencies can take to further improve diversity within genetic research, and thus, precision medicine.

Precision medicine will likely become a game changer for many patients and their family members. In order for precision medicine’s benefits to reach as many people as possible, we need to have a diverse population of research participants today.