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Journal of Breast Cancer Research

ISSN: 2769-2418

Original Research Open Access
Volume 6 | Issue 1 | DOI: https://doi.org/10.46439/breastcancer.6.037

Uncovering genetic variations in HTR2A and miRNAs drivers of breast cancer risk in African American women

Nicole Retland1,+, Karl M. Thompson2,+, Joseph I. Aubee2, Victor Apprey3, Somiranjan Ghosh4, Robert Copeland5, Yasmine Kanaan2, Yayin Fang6, Ali Ramadan7, Hassan Brim7, Muneer M. Abbas2,3,*
  • 1Fielding Graduate University, Center for the Advancement of STEM Leadership, Santa Barbara, CA, USA
  • 2Howard University, Department of Microbiology, Washington, DC, USA
  • 3The National Human Genome Center, Howard University, Washington, DC, USA
  • 4Howard University, College of Arts and Sciences, Washington, DC, USA
  • 5Howard University, Department of Pharmacology, Washington, DC, USA
  • 6Howard University, Department of Biochemistry, Washington, DC, USA
  • 7Howard University, Department of Pathology, Washington, DC, USA
  • +Equally contributed as first authors
+ Affiliations - Affiliations

Corresponding Author

Muneer M. Abbas, m_abbas@howard.edu

Received Date: May 14, 2026

Accepted Date: June 09, 2026

Citation:

Retland N, Thompson KM, Aubee JI, Apprey V, Ghosh S, Copeland R, et al. Uncovering genetic variations in HTR2A and miRNAs drivers of breast cancer risk in African American women. J Breast Cancer Res. 2026;6(1):65-83.


Copyright: © 2026 Retland N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background/Objectives: Triple-negative breast cancer (TNBC) disproportionately affects African American (AA) women, yet the molecular mechanisms remain poorly understood. Emerging evidence suggests that microRNAs (miRNAs) may play a critical role in cancer progression. This study investigated the association of HTR2A genetic variants and miRNA dysregulation in AA women with breast cancer.

Methods: A total of 417 AA women (192 with breast cancer, 225 controls) were genotyped for selected HTR2A SNPs. Functional predictions and molecular modeling assessed structural impact. TNBC cell lines were treated with an HTR2A agonist, and miRNA expression was profiled using the NanoString, and bioinformatic tools were applied to identify miRNA targets and associated oncogenic pathways. 

Results: Three SNPs (rs6304, rs6311, and rs1745837) were significantly associated with breast cancer risk (e.g., rs6311 dominant model: OR = 11.98, 95% CI: 6.63–21.66, p < 0.0001). The rs6304 demonstrated predicted protein destabilization. Six oncogenic miRNAs (including miR-92a-3p and miR-377-3p) were significantly upregulated (p < 0.05) and involved in PI3K/AKT, JAK/STAT, and IL-6 pathways. 

Conclusions: HTR2A genetic variation, miRNA dysregulation, and increased breast cancer risk in AA women. These findings suggest that HTR2A variants and miRNA profiles may serve as potential biomarkers for risk stratification and targeted therapeutic approaches in TNBC.

Simple Summary: African American women face a higher risk of developing a particularly aggressive type of breast cancer called TNBC. This study explores how changes in a specific serotonin receptor gene, known as HTR2A, might contribute to this risk. By analyzing the DNA of AA women and conducting lab experiments, the researchers identified genetic variations that are more common in women with breast cancer. They also discovered that these genetic changes may affect the way small molecules called microRNAs control cell growth. Understanding these links may help scientists find better ways to detect and treat breast cancer in AA women, paving the way for more personalized and effective medical care.

Keywords

Triple-Negative breast cancer, African American women, HTR2A gene, Single nucleotide polymorphisms, microRNA, Gene regulation, Breast cancer disparities, Precision medicine

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