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Background & Objective: Letrozole is a standard aromatase inhibitor for postmenopausal women with estrogen receptor-positive breast cancer, but biomarker profiles and treatment tolerability vary among patients. This study described the distributions of ESR1 rs2234693 and rs9340799 and explored their relationships with letrozole-related biomarkers and self-reported symptoms in an Iraqi cohort.
Materials & Methods: This exploratory cross-sectional pharmacogenetic study included 100 postmenopausal women receiving letrozole 2.5 mg daily for at least three months. ESR1 variants were genotyped using allele-specific PCR/ARMS-PCR. Estradiol, CA15-3, calcium, osteocalcin, and bone-specific alkaline phosphatase were measured, and treatment-related symptoms were recorded. Genotype associations were examined under the three-genotype, dominant, and recessive models; logistic regression estimates were unadjusted.
Results: For rs2234693, genotype frequencies were TT 29 (29%), TC 28 (28%), and CC 43 (43%); the T and C allele frequencies were 43% and 57%, respectively. The distribution deviated from Hardy–Weinberg equilibrium. All participants carried the rs9340799 AA genotype, precluding association testing. Under the dominant rs2234693 model, TC/CC carriers had higher CA15-3 concentrations than TT carriers (nominal P = 0.036; Benjamini–Hochberg false-discovery-rate [FDR] q = 0.378). Hair loss was reported in 44.8% of TT carriers and 23.9% of TC/CC carriers (Fisher exact P = 0.054). Crude logistic regression yielded an OR of 0.39 (95% CI: 0.16–0.97; P = 0.042); after adjustment for age, body mass index, and letrozole duration, the OR was 0.34 (95% CI: 0.13–0.88; P = 0.026).
Conclusion: ESR1 rs2234693 showed substantial variability in this Iraqi cohort, whereas rs9340799 was monomorphic. No genotype–outcome association remained significant after FDR correction. The nominal CA15-3 and hair-loss signals require independent prospective validation before any clinical application.
Materials & Methods: This exploratory cross-sectional pharmacogenetic study included 100 postmenopausal women receiving letrozole 2.5 mg daily for at least three months. ESR1 variants were genotyped using allele-specific PCR/ARMS-PCR. Estradiol, CA15-3, calcium, osteocalcin, and bone-specific alkaline phosphatase were measured, and treatment-related symptoms were recorded. Genotype associations were examined under the three-genotype, dominant, and recessive models; logistic regression estimates were unadjusted.
Results: For rs2234693, genotype frequencies were TT 29 (29%), TC 28 (28%), and CC 43 (43%); the T and C allele frequencies were 43% and 57%, respectively. The distribution deviated from Hardy–Weinberg equilibrium. All participants carried the rs9340799 AA genotype, precluding association testing. Under the dominant rs2234693 model, TC/CC carriers had higher CA15-3 concentrations than TT carriers (nominal P = 0.036; Benjamini–Hochberg false-discovery-rate [FDR] q = 0.378). Hair loss was reported in 44.8% of TT carriers and 23.9% of TC/CC carriers (Fisher exact P = 0.054). Crude logistic regression yielded an OR of 0.39 (95% CI: 0.16–0.97; P = 0.042); after adjustment for age, body mass index, and letrozole duration, the OR was 0.34 (95% CI: 0.13–0.88; P = 0.026).
Conclusion: ESR1 rs2234693 showed substantial variability in this Iraqi cohort, whereas rs9340799 was monomorphic. No genotype–outcome association remained significant after FDR correction. The nominal CA15-3 and hair-loss signals require independent prospective validation before any clinical application.
فهرست منابع
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