Journal of Advances in Medical and Biomedical Research

en Association of ESR1 rs2234693 Polymorphism with Letrozole-Related Biomarker and Tolerability Outcomes in Iraqi Postmenopausal Women with Estrogen Receptor-Positive Breast Cancer Life Science Life Science مقاله پژوهشی Original Research Article 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. ESR1, Letrozole, Breast Cancer, Pharmacogenetics, rs2234693, rs9340799, Iraqi Patients 50 50 http://journal.zums.ac.ir/browse.php?a_code=A-10-7570-1&slc_lang=en&sid=1 Sajad Hassan Sabir SajadHassanSabir@gmail.com 5200319475328460090462 5200319475328460090462 No Department of Pharmacology and Toxicology, College of Pharmacy, University of Kerbala, Karbala, Iraq Zahraa Abd Al-Kareem ZahraaAbdAl-Kareem@gmail.com 5200319475328460090463 5200319475328460090463 No Department of Pharmacology and Toxicology, College of Pharmacy, University of Kerbala, Karbala, Iraq Shaima Jabbar shaymaa.a@uokerbala.edu.iq 5200319475328460090464 5200319475328460090464 Yes Department of Pharmacology and Toxicology, College of Pharmacy, University of Kerbala, Karbala, Iraq Ali Abd Al-Rasool Al-Mukhtar AliAbdAl-RasoolAl-Mukhtar@gmail.com 5200319475328460090465 5200319475328460090465 No Ali Abd Al-Rasool Al-Mukhtar Department of Oncology and Radiotherapy, Al-Imam Al-Hassan Al-Mujtaba Teaching Hospital, Kerbala Health Directorate, Karbala, Iraq