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1- Department of Pharmacology and Toxicology, College of Pharmacy, University of Kerbala, Karbala, Iraq
2- Department of Pharmacology and Toxicology, College of Pharmacy, University of Kerbala, Karbala, Iraq , shaymaa.a@uokerbala.edu.iq
3- Ali Abd Al-Rasool Al-Mukhtar Department of Oncology and Radiotherapy, Al-Imam Al-Hassan Al-Mujtaba Teaching Hospital, Kerbala Health Directorate, Karbala, Iraq
Abstract:   (1 Views)
Methods: This exploratory cross-sectional pharmacogenetic study enrolled 100 Iraqi postmenopausal women with estrogen receptor-positive breast cancer who had received letrozole 2.5 mg once daily for at least three months. ESR1 rs2234693 was selected as the primary variant for genotype–phenotype analysis, whereas rs9340799 was additionally genotyped for descriptive purposes. Genotyping was performed using allele-specific PCR/ARMS-PCR and visualized and interpreted by agarose gel electrophoresis. The assessed biomarkers included estradiol, CA15-3, calcium, osteocalcin, and bone-specific alkaline phosphatase. Letrozole-related symptoms were assessed clinically.
Results: ESR1 rs2234693 genotype frequencies were 29% for TT, 28% for TC, and 43% for CC, with corresponding T and C allele frequencies of 43% and 57%, respectively. In contrast, ESR1 rs9340799 was monomorphic, as all participants carried the AA genotype; therefore, subsequent association analyses were limited to rs2234693. Under the dominant genetic model for rs2234693, TC/CC carriers showed a nominal exploratory association with higher CA15-3 levels compared with TT carriers (P = 0.036), whereas no significant differences were observed in estradiol or bone-related biomarkers. In exploratory logistic regression, TC/CC carriers showed lower odds of hair loss than TT carriers (OR = 0.39, 95% CI: 0.16–0.97; P = 0.042).
Conclusion: ESR1 rs2234693 showed appreciable variability in this Iraqi cohort and produced limited nominal exploratory associations with CA15-3 and hair loss. These findings require prospective validation before clinical implementation.
     
Type of Study: Original Research Article | Subject: Life Science
Received: 2026/07/17 | Accepted: 2026/08/22

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