Is an Anti-Malaria Gene Tied to Triple-Negative Breast Cancer?

University of Illinois Cancer Center Director Jan Kitajewski’s laboratory is tackling triple-negative breast cancer by investigating whether a common genetic mutation that protects people from some types of malaria is potentially making them more susceptible to an aggressive form of cancer.

The Kitajewski lab is focusing on ACKR1, a gene that encodes the Duffy antigen. A mutation in this gene prevents carriers from becoming ill from certain types of malaria-causing parasites.  The Duffy antigen, located on red blood cells and blood vessels, is not expressed on red blood cells in people with the mutation.

Common in individuals of sub-Saharan African descent, genetic mutations in ACKR1 can also be found among members of some Jewish and Middle Eastern ethnic groups. 

About 70% of Americans of West African ancestry carry this common mutation in ACKR1, which eliminates the Duffy antigen from their red blood cells. The Duffy antigen allows malaria-causing blood parasites to infiltrate red blood cells. People with the mutation in the ACKR1 gene are essentially immune to common forms of malaria endemic to West and Central Africa.

Understanding role of the ACKR1 protein at a cellular level may help scientists understand why triple-negative breast cancer is more common or more aggressive among Black women, Kitajewski said.

“Genetic determinants of health are an important field of study as scientists look to explain population-specific differences in cancer and other diseases,” Kitajewski explained. “Understanding the role of genetics in cancers, along with the role of social determinants, helps us understand factors that disproportionately affect certain populations. The hope is that knowledge of ACKR1 can lead us to better treatments and outcomes for all patients.”

Building on research conducted at Weill Cornell Medicine, where investigators hypothesized that ACKR1 mediates ancestry-specific inflammatory responses, the Kitajewski lab is pursuing research that explores the body’s immune response to triple-negative breast cancer, looks at the role of ACKR1 in tumors, and investigates how cancer cells interact when the Duffy antigen is present.

Triple-negative breast cancer is considered the most aggressive and lethal form of breast cancer. It is more likely to be diagnosed in Black or Hispanic women, people younger than 50 and those with the BRCA1 mutation. Comprising 10-20% of breast cancers, triple-negative breast cancer is harder to treat, it does not respond to hormone therapy and thus effective therapies are limited.

The Cancer Center’s Breast Cancer Working Group has previously conducted molecular analysis that found early stage hormone-receptor positive breast cancer in Black women is more likely to be resistant to common treatments.  

The Cancer Center is launching a tissue microarray (TMA) of breast tumors from diverse patients to help scientists investigate genetic differences that contribute to disproportionate mortality rates among Black women. The TMA includes both hormone-receptor positive and triple-negative breast cancers.

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