Researcher Studies Protein Variants in Prostate Cancer

Norman Lee was awarded $1.8 million to study genetic factors that contribute to high mortality rates in African American men with prostate cancer.

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June 07, 2017

By Kristen Mitchell

A George Washington University researcher was awarded a $1.8 million grant to study genetic factors that make prostate cancer nearly three times more deadly in African American men compared to their European or Asian American counterparts.

Norman Lee, a professor and researcher in the School of Medicine and Health Sciences, has spent the past five years studying prostate cancer disparities. He believes differences in gene expression, polymorphisms and mutations are partially to blame for the increased risk of death for African American men with prostate cancer. These differences can make tumors more aggressive and less responsive to current treatments, Dr. Lee said.

African American men and European or Asian men carry the same complement of genes. However, certain polymorphisms and mutations found more frequently in the African American population are linked to increased risk of prostate cancer, Dr. Lee said.

Dr. Lee believes differences in RNA splicing between African and European American men may also play a role in prostate cancer disparities. In the body, genes are transcribed into mRNA and the resulting mRNA undergoes differential splicing, a regulated process that allows a single gene to generate multiple mRNA versions or variants. Each variant codes for a slightly different protein with different activity. The process of differential splicing allows cancer cells from African Americans to make different protein variants compared to cancer cells from European Americans.

“We’re finding specific mRNA variants that are preferentially expressed in African American cancers, and these variants encode signal transduction proteins that are over-active,” Dr. Lee said. “We believe this phenomenon may drive the aggressiveness of prostate cancer in African Americans. We have also discovered mRNA variants that code for proteins that are resistant to specific targeted therapies used in the treatment of cancer.”

The National Cancer Institute within the National Institutes of Health awarded Dr. Lee a five-year, $1.8 million grant in March to study mRNA variants found specifically in the African American population and how mRNA splicing impacts cancer.

Identifying these different variants would help physicians treat patients with aggressive forms of cancer through precision medicine, Dr. Lee said.

“We know that some patients respond to therapy, while other patients do not respond to therapy due to polymorphisms, mutations and mRNA splicing,” he said. “By identifying these events in tumors prior to therapy, treatments can be tailored to the patient. Ideally it would be better if you were to identify which patients were responsive and which were non-responsive to therapies ahead of time. This would allow physicians to sidestep any treatment options that would be ineffective based on a patient’s specific genetic profile.”

There is still a lot to learn in terms of cancer disparities, Dr. Lee said, and there are multiple sociological and epidemiological factors that contribute to the disparities. African Americans are less likely to have access to affordable health care, which creates a delay in diagnosis and treatment, Dr. Lee said.

Even after epidemiological factors have been accounted for, however, African American men have a 1.5 to two times higher prostate cancer incidence and mortality, Dr. Lee said.

“That difference, even after taking into account epidemiological factors, is what we refer to as the biological factors,” he said. “That is where genetics come in.”

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