Cancer Mechanisms Driven by Social Stress Factors That Help Explain Racial Disparities

 Racism and poverty, for example, alter cellular functions that promote tumor growth and proliferation.

DURHAM, NC – According to a study led by Duke Cancer Institute researchers, chronically stressful daily conditions such as racism, pollution, and poverty have a direct impact on the cellular mechanisms that drive lethal, invasive forms of breast cancer.

The findings, which were published on June 13 in the journal npj Breast Cancer, shed light on one of the most pervasive health disparities between White and Black people. Black women have higher incidences and lower survival rates for aggressive subtypes of breast cancer, such as triple negative and inflammatory breast cancers, than White women.

"When it comes to breast cancer, these disparities are global, not just in the United States," said senior author

"When it comes to breast cancer, these disparities are global, not just in the United States," said senior author Gayathri Devi, Ph.D., an associate professor in Duke's departments of Surgery and Pathology and the program director of the Duke Consortium for Inflammatory Breast Cancer at Duke Cancer Institute. "There is a complex interplay between societal stress factors - access to care, racism, pollution, and the many problems associated with poverty - and the impact these stresses have inside the body at the molecular level."

"Exposure to these stress factors has spanned generations and geographies among people of African ancestry, resulting in population- and individual-level differences in physiology, genetics, and genomics," Devi explained.

Using The Cancer Genome Atlas, Devi and colleagues identified specific genes from a set of 226 genetic patterns of adaptive stress response that differ depending on the breast cancer subtype. These stress response genes are involved in cancer development by regulating cell life cycles, DNA damage response, signaling pathways, and cell death-related processes.

"Previous research from our lab and others shows that tumor cells respond differently to cellular stress than normal cells," Devi explained. "When normal cells are exposed to stress, they halt protein synthesis and repair any gene changes." If they are unable to repair themselves, the process of cell death begins.

"With chronic stress, tissues and cells in the body react and adapt differently," Devi explained. "This study looked into that process." Allostatic load is a term that describes the cumulative burden of chronic stress and life events that occur in individuals and even populations of people."

Tumor cells adapt to chronic stress by developing a high tolerance for stress, avoiding the normal cell death process and continuing to proliferate. The activation of 29 of these stress response genes differed according to race.

The study also linked gene sets known to be involved in cancer signaling and oxidative stress response to poorer breast cancer patient survival outcomes.

Because Black patients' breast tumors have higher levels of oxidative stress markers than White patients', Devi believes the findings emphasize the importance of understanding the underlying biology of aggressive breast cancer subtypes as part of the diagnosis and treatment process.

"Where there are race- and/or ancestry-related disparities in incidence, treatment, and survival outcomes, identifying tumor biology has the potential to aid in the development of new biomarkers and treatment strategies to mitigate these disparities," Devi explained.

Authors of the study, in addition to Devi, include Muthana Al Abo, Larisa Gearhart-Serna, and Steven

Van Laere, Jennifer A. Freedman, Steven R. Patierno, Eun-Sil Shelley Hwang, Savitri Krishnamurthy, and Kevin P. Williams are among those who have contributed to this work. The Duke Consortium for IBC has a long history of collaboration with researchers at the University of Antwerp, MD Anderson Cancer Center, and North Carolina Central University.

The National Cancer Institute (3P20CA202925-04S2, R01CA264529), the National Institutes of Health (R01CA220314), the Department of Defense (W81XWH-17-1-0297), the Duke School of Medicine Bridge Award, The IBC Network Foundation Gift and the Prostate Cancer Foundation Movember Challenge Award all contributed to the study.


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