Abstract

Background: Breast carcinoma is the most common cancer among women worldwide, accounting for 36% of cancer cases with 2.089 million diagnoses in 2018, mainly in affluent countries. Factors such as hypoxia, marked by HIF-1α levels, contribute to increased aggressiveness and resistance in tumors. Additionally, fibronectin plays a crucial role in the tumor microenvironment by enhancing progression, metastasis, cell growth, and angiogenesis, despite its variable expression due to cellular senescence. This study aims to investigate the association between the single nucleotide-polymorphism (SNP) G473A (rs1800449) of LOX with breast cancer development in Iraqi women, analyzing its correlation with serum levels of HIF-1 α and fibronectin. The study also explored the potential of these serum markers as diagnostic biomarkers for breast cancer. Method: This case-control study involved 90 participants, comprising 45 females with newly diagnosed breast cancer and 45 matched healthy controls, approved ethically by the Committee of the College of Pharmacy, University of Baghdad. Participants were categorized into groups based on breast cancer type: (12) invasive lobular carcinoma, (24) invasive ductal carcinoma, (9) mixed, with 45 healthy women as controls. Blood samples were analyzed for SNPs, genetic analysis of the G473A (rs1800449) gene, and serum HIF-1α and fibronectin levels. Statistical analysis was performed using SPSS, employing non-parametric tests due to the non-normal distribution. The median (IQR) was used as descriptive statistics. Spearman correlation analyses were used to assess the correlation between the studied markers, and ROC curve analysis was performed to evaluate sensitivity and specificity, with a significance level of p < 0.05. Result: The study found no significant differences in median (IQR) for age, height, weight, or BMI. Likewise, educational levels, family history, and hormonal contraceptive use showed no significant variations. However, breast cancer patients showed significantly higher serum HIF-1α and Fibronectin levels compared to the control group (P < 0.0001), with a strong correlation between HIF-1α and Fibronectin levels (ρ = 0.817). The rs1800449 SNP analysis indicated significant differences in serum HIF-1α and Fibronectin levels among CC and CT genotypes; the CT variant in patients showed elevated HIF-1α levels compared to CC and TT variants, while fibronectin levels showed no significant difference across genotypes (P = 0.589). Conclusion: The study found no significant differences in demographic and lifestyle factors between breast cancer patients and controls. However, breast cancer patients exhibited higher plasma levels of HIF-1α and Fibronectin, with a strong positive correlation between these biomarkers. Genetic analysis of the rs1800449 SNP revealed that the CT genotype was associated with significantly elevated HIF-1α levels compared to CC and TT genotypes, while Fibronectin levels showed no variation across genotypes.