Can Genomic Data Reduce Racial Disparities in Cancer Outcomes?

After analyzing the genomic data of men of different races, researchers believe that a combination of socioeconomic and biological factors may contribute to racial disparities in prostate cancer outcomes, according to a study published in Clinical Cancer Research.

Although prostate cancer is the most common type of cancer among American men after skin cancer, the disease impacts some patient populations more than others.

Researchers from the Moffitt Cancer Center noted that African American men are twice as likely to develop prostate cancer, and more often have an aggressive form of the disease that spreads rapidly. African American men are also twice as likely to die from prostate cancer than their white counterparts.

The healthcare industry has recognized these disparities, and researchers have continually sought to discover the reasons behind gaps in prostate cancer outcomes.

In commentary recently published in JAMA Network Open, Willie Underwood, MD, of the Buffalo Community Center for Health Equity discussed prostate cancer disparities and highlighted how important it is for providers to understand the causes of poor outcomes.

“Clinicians need better tools to detect prostate cancer as early as possible. If fear of treatment adverse effects influence treatment decision-making, then it is the duty of healthcare researchers and practitioners to improve treatments and reduce adverse effects,” he wrote.

“If there is a genetic cause for black men presenting with more advanced disease at diagnosis, the important question is whether this genetic cause can be overcome by early detection and appropriate treatment.”

In the Clinical Cancer Research study, the Moffitt Cancer Center team aimed to take a closer look at the genomic features of prostate cancer tumors among men of different races.

Researchers analyzed whole transcriptome data from nearly 1,200 proctectomy samples in the Decipher Genomic Resource Information Database registry. Transcriptomic data provides a complete look at all the RNA sequences within a cell, which in turn can show when and where each gene is turned on or off.

The group focused on 1,260 immune specific genes to determine differences between prostate cancer tumor cells in African American and European American men.

The results showed that there are significant differences between the two races. Major immune pathways, including cytokine, interferon and interleukin signaling, are elevated in African American prostate tumors.

These pathways contribute to and escalate the growth and spread of cancer cells. The immune biologic signatures suggest that prostate cancer tumors in African American men may be more sensitive to radiotherapy, and could have a better response to immunotherapy.

The results could lead to more personalized treatments for African American men with prostate cancer, the team stated.

“Currently there are only two immunotherapy options for prostate cancer patients: the sipuleucel-T cell vaccine and pembrolizumab. However, not everyone responds to those therapies,” said Kosi Yamoah, MD, PhD, associate member and director of cancer disparities research in the departments of Radiation Oncology and Cancer Epidemiology at Moffitt.

“Our study shows that African American men have higher overall immune content within their tumor microenvironment and higher expression of T lymphocytes. We can use that information to select a therapy that better targets their tumor and therefore improve their outcome.”

The researchers also found six genes that expression levels were consistently different between African American and European American men. One gene, IFITM3, is an indicator that a patient has a significantly higher risk of biochemical recurrence, meaning that their prostate antigen score continues to rise even after radiation or surgery. This gene also appears to play an important role in metastasis.

Further research is necessary to determine whether their findings can have a positive impact on the treatment of African American men with prostate cancer, but the results could help lead to more targeted therapies for individual patients.

“Previous studies have looked at the immune landscape of prostate cancer in white or European American men but have lacked validation among their African American counterparts,” said Yamoah.

“Our genomic analysis, the largest of its kind, revealed there are major immune pathways that are significantly elevated in African American men, which can correlate with risk of cancer recurrence and poor outcomes.”

Studies like these have the potential to accelerate the development of precision medicine approaches and reduce health disparities among racial and ethnic minorities. A 2019 study conducted by researchers from Rutgers University showed that studying the genetic mutations of diverse populations could be the key to more personalized care delivery.

“In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities,” the group said.

“Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific.”