INFLUENCE OF LYSYL OXIDASE (RS1800449) GENE VARIATION ON SERUM TGF-Β1, LYSYL OXIDASE, AND HOMOCYSTEINE AND ITS POTENTIAL IMPLICATIONS FOR TARGETED DRUG THERAPY IN HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR-2-POSITIVE BREAST CANCER AMONG NEWLY DIAGNOSED IRAQI WOMEN
DOI:
https://doi.org/10.22159/ajpcr.2026v19i6.59282Keywords:
Breast cancer, Lysyl oxidase (LOX) polymorphism, therapeutic implications, rs1800449, Homocysteine, Transforming growth factor-β1 (TGF-β1)Abstract
Objective: The objective of this study was to evaluate the association between lysyl oxidase (LOX) rs1800449 (G473A) gene polymorphism and circulating biomarkers, including homocysteine (Hcy), LOX, and transforming growth factor-β1 (TGF-β1), in newly diagnosed Iraqi women with breast cancer.
Methods: A case–control study was conducted between January and June 2025, including 90 participants: 45 newly diagnosed breast cancer patients (18 human epidermal growth factor receptor 2 [HER2]-positive and 27 HER2-negative) and 45 age- and body mass index-matched healthy controls. Venous blood samples (8 mL) were collected for DNA extraction and biochemical analysis. LOX rs1800449 polymorphism was determined using polymerase chain reaction-based genotyping, whereas serum Hcy, LOX, and TGF-β1 concentrations were measured using enzyme-linked immunosorbent assay kits.
Results: Statistical significance was defined as p< 0.05. Median serum levels of Hcy (3096.9 vs. 350.9 ng/mL), LOX (28.9 vs. 3.6 ng/mL), and TGF-β1 (6.8 vs. 0.8 ng/mL) were significantly higher in breast cancer patients compared with those in controls (all p<0.001).
Conclusion: Elevated biomarker levels were observed in both HER2-positive and HER2-negative subgroups without statistically significant inter-subtype differences (p>0.05). Strong positive correlations were identified among Hcy, LOX, and TGF-β1 (ρ=0.710–0.790, p<0.001). CT and TT genotypes of the rs1800449 showed numerically higher frequency in patients, but differences were not statistically significant (p>0.05). LOX rs1800449 polymorphism was associated with elevated circulating Hcy, LOX, and TGF-β1 levels in newly diagnosed breast cancer patients, supporting a linked metabolic–extracellular matrix remodeling–pro-fibrotic biological signature.
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