In the Journals

Gene variants could shed light on racial disparities in breast cancer outcomes

Variants in the DARC/ACKR1 gene associated with sub-Saharan African origins may explain why black women have worse breast cancer outcomes than white women, according to results of a study published in Cancer Epidemiology, Biomarkers & Prevention.

“This work is the first to identify a potential driver of tumor immune response in breast cancer that is definitively linked to sub-Saharan West African ancestry,” Melissa B. Davis, MD, associate professor of cell and developmental biology research in surgery at Weill Cornell Medicine, and scientific director of the International Center for the Study of Breast Cancer Subtypes, said in a press release. “I think we are finally on track to characterize a specific tumor phenotype and tumor microenvironment differences that are driving race-group disparities in cancer mortality that transcend the traditional social determinants of disparities.”

Disparities in breast cancer rates among individuals of different races and ethnicities have been studied for several decades and have largely focused on socioeconomic factors and health care availability. However, studies in recent years have demonstrated that biological factors may be linked to more aggressive types of disease.

In this case-control cohort study, Davis and colleagues looked at DARC/ACKR1 gene expression levels in breast tumor tissue from African-American (n = 167) and white American (n = 671) patients with breast cancer in the Cancer Genome Atlas Breast Cancer cohort. They also evaluated serum samples from sets of patients recruited from the University Cancer and Blood Center in Athens, Georgia (n = 41) and Henry Ford Health System in Detroit (n = 225).

Researchers conducted linear regression analyses for gene correlations in molecular subtypes and phenotypes and nominal logistical regressions across derived tumor status. They measured DARC/ACKR1 subtypes for associations with demographics and clinical variables.

Results showed that breast tumors from African-American patients had lower expression levels of DARC/ACKR1 genes compared with white American patients.

Having lower DARC/ACKR1 expression levels appeared associated with more aggressive tumor growth, whereas higher expression levels correlated with longer survival.

Patients with West African ancestry had lower levels of the CCL2 chemokine protein and higher levels of the CXCL8 chemokine protein. Higher CCL2 and lower CXCL8 levels correlated with longer survival.

Across all molecular tumor subtypes, patients with higher DARC/ACKR1 tumor expression demonstrated longer OS (P < 2.2 x 10) and RFS (P < 1 x 10¹).

Confounding factors within cohorts that could not be separated from variables of interest served as limitations to this study.

Lisa Newman, MD
Lisa Newman, MD

“In the future, we may be able to measure the level of DARC/ACKR1 expression in biopsied breast tissue to identify patients who are likely to benefit from more aggressive therapy,” Lisa Newman, MD, chief of the section of breast surgery at New York-Presbyterian/Weill Cornell Medical Center, said in a press release. – by John DeRosier

Disclosure s : Newman reports prior employment at Henry Ford Health System. Another study author reports a consultant role and ownership interest in Riptide Biosciences. Davis and the other authors report no relevant financial disclosures.

Variants in the DARC/ACKR1 gene associated with sub-Saharan African origins may explain why black women have worse breast cancer outcomes than white women, according to results of a study published in Cancer Epidemiology, Biomarkers & Prevention.

“This work is the first to identify a potential driver of tumor immune response in breast cancer that is definitively linked to sub-Saharan West African ancestry,” Melissa B. Davis, MD, associate professor of cell and developmental biology research in surgery at Weill Cornell Medicine, and scientific director of the International Center for the Study of Breast Cancer Subtypes, said in a press release. “I think we are finally on track to characterize a specific tumor phenotype and tumor microenvironment differences that are driving race-group disparities in cancer mortality that transcend the traditional social determinants of disparities.”

Disparities in breast cancer rates among individuals of different races and ethnicities have been studied for several decades and have largely focused on socioeconomic factors and health care availability. However, studies in recent years have demonstrated that biological factors may be linked to more aggressive types of disease.

In this case-control cohort study, Davis and colleagues looked at DARC/ACKR1 gene expression levels in breast tumor tissue from African-American (n = 167) and white American (n = 671) patients with breast cancer in the Cancer Genome Atlas Breast Cancer cohort. They also evaluated serum samples from sets of patients recruited from the University Cancer and Blood Center in Athens, Georgia (n = 41) and Henry Ford Health System in Detroit (n = 225).

Researchers conducted linear regression analyses for gene correlations in molecular subtypes and phenotypes and nominal logistical regressions across derived tumor status. They measured DARC/ACKR1 subtypes for associations with demographics and clinical variables.

Results showed that breast tumors from African-American patients had lower expression levels of DARC/ACKR1 genes compared with white American patients.

Having lower DARC/ACKR1 expression levels appeared associated with more aggressive tumor growth, whereas higher expression levels correlated with longer survival.

Patients with West African ancestry had lower levels of the CCL2 chemokine protein and higher levels of the CXCL8 chemokine protein. Higher CCL2 and lower CXCL8 levels correlated with longer survival.

Across all molecular tumor subtypes, patients with higher DARC/ACKR1 tumor expression demonstrated longer OS (P < 2.2 x 10) and RFS (P < 1 x 10¹).

Confounding factors within cohorts that could not be separated from variables of interest served as limitations to this study.

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Lisa Newman, MD
Lisa Newman, MD

“In the future, we may be able to measure the level of DARC/ACKR1 expression in biopsied breast tissue to identify patients who are likely to benefit from more aggressive therapy,” Lisa Newman, MD, chief of the section of breast surgery at New York-Presbyterian/Weill Cornell Medical Center, said in a press release. – by John DeRosier

Disclosure s : Newman reports prior employment at Henry Ford Health System. Another study author reports a consultant role and ownership interest in Riptide Biosciences. Davis and the other authors report no relevant financial disclosures.