Preventing disparities in gene-based therapeutics and diagnostics

Writing in the August issue of Health Affairs, Tufts University researcher Dr. José M. Ordovás and colleagues noted that for all their promise, genetically based therapeutics and diagnostics still fall short of being representative of—and applicable to—the population as a whole.

In particular, the team noted a potential lack of benefits for such advances with regard to “disadvantaged” groups—that is, their paper “Using Genetic Technologies To Reduce, Rather Than Widen, Health Disparities” was concerned in large part with racial and ethnic groups that are not well represented in many clinical trials.

As their abstract notes, “Evidence shows that both biological and nonbiological factors contribute to health disparities. Genetics, in particular, plays a part in how common diseases manifest themselves. Today, unprecedented advances in genetically based diagnoses and treatments provide opportunities for personalized medicine. However, disadvantaged groups may lack access to these advances, and treatments based on research on non-Hispanic whites might not be generalizable to members of minority groups. Unless genetic technologies become universally accessible, existing disparities could be widened. Addressing this issue will require integrated strategies, including expanding genetic research, improving genetic literacy, and enhancing access to genetic technologies among minority populations in a way that avoids harms such as stigmatization.”

Focusing on breast cancer and chronic kidney disease, the authors showed that even as genetic and molecular knowledge has advanced in combating such diseases in the past decade, “significant racial and ethnic health disparities persist and hinder universal progress,” as a Tufts University article about their work put it. The policy recommendations they propose are:

Increasing the enrollment of non-white participants in research on complex diseases.
Community-based participatory research to promote genetic literacy and encourage more volunteers to become involved in research.
Funding research on the interactions of genes and the environment.
Educating healthcare providers as well as patients about the risks, benefits and limitations of genetic research.

“We need to collect more data from groups for whom we currently have insufficient information so that we can improve care for all individuals. If we don’t expand our efforts, the quality and effectiveness of genetic research and services will be limited in ways that can perpetuate health disparities,” said Ordovás, senior author of the paper and the director of the Nutrition and Genomics Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. “The Precision Medicine Initiative for one will be a big step forward in this endeavor and is to be commended for including community-based health provider organizations in its network to attract volunteers. Increasing diversity in research and testing will help maximize the possibilities of precision medicine.”

According to the authors, three key areas where their recommendations would make improvements are incomplete genetic databases, inadequate treatment options and insufficiently understood disease mechanisms.

People with non-European ancestries are underrepresented in genetic databases, limiting the ability to apply genetic knowledge to reduce disease in these groups, they note. Researchers know that hereditary breast cancer is linked to mutations in the BRCA1 or BRCA2 genes, but the “normal” genetic sequence for these genes was determined based on women of European and Ashkenazi Jewish descent.

Meanwhile, studies show that African-American and Hispanic women are much less likely than white women to receive genetic counseling or testing for hereditary breast cancer. As the Tufts team points out, the absence of this data perpetuates an incomplete genetic database on which clinical decisions about treating breast cancer rely.

As the Tuft article about the paper noted, for many diseases, clinical advances in treatment have developed based on new knowledge of genetic markers. Studies show that non-Hispanic black women tend to be diagnosed with more advanced sporadic breast cancer (occurring without family history) compared to white women. Many potential genetic markers might explain the racial and ethnic disparity in tumor aggressiveness in sporadic cancer. However, the small number of tumor samples from non-European women offers inadequate details about patient and tumor characteristics and restricts the use of genetic knowledge in clinical treatments for all individuals.

Similarly, Tufts notes, treatments tailored to individuals with high-risk genotypes for certain diseases have not yet been identified because the molecular mechanisms behind the diseases are unknown as well. Researchers know that African-Americans are disproportionately affected by variants in the APOL1 gene, which can increase a person’s risk of kidney disease by up to seven times. Due to insufficient understanding of the molecular mechanisms by which the gene increases disease risk, effective treatments elude clinicians.

“Ultimately, we want the knowledge gained from a reduction in health disparities to lead to an increase in treatments for people who are most at risk. If we understand the aggressive breast cancer subtype that more frequently affects black women, we might be able to expand treatment options. We want to look at environmental factors as well as tumor biology to know how they contribute to the disease, and how we might then attack it,” said first author Dr. Caren E. Smith, a scientist in Ordovás’ lab.