Document Type : Research Articles
Authors
1
Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
2
Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.
3
Genetics of Non- Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
4
Clinical Immunology Research Center, Department of Internal Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
5
Children and Adolescent Health Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.
Abstract
Objective: Breast cancer (BC) is the most common cancer among women globally, with Iranian women showing an earlier onset compared to those in Western countries. Genetic variations in the PI3K/AKT/mTOR signaling pathway have been implicated in cancer susceptibility, but limited studies exist on the association of these polymorphisms with BC risk in the Iranian population. This study aimed to investigate the associations of specific polymorphisms in the AKT1, PIK3CA, and mTOR genes with BC susceptibility in an Iranian population. Methods: A case-control study was conducted with 222 confirmed BC patients and 230 cancer-free controls. Genotyping of AKT1 rs1130214 and rs1130233, PIK3CA rs6443624, and mTOR rs1883965 polymorphisms was performed using PCR-RFLP methods. Statistical analysis was carried out using logistic regression to evaluate the associations between genotypes and BC risk. Results: The AKT1 rs1130214 polymorphism was associated with a significantly reduced BC risk (codominant model: OR=0.44, 95% CI=0.30-0.65, p<0.001; allelic model: OR=0.52, 95% CI=0.38-0.72, p<0.001). Conversely, AKT1 rs1130233, PIK3CA rs6443624, and mTOR rs1883965 polymorphisms were linked to an increased BC risk in various inheritance models. For instance, the mTOR rs1883965 G>A variant showed a significantly higher risk (dominant model: OR=2.75, 95% CI=1.84-4.12, p<0.001). Conclusion: This study indicates that polymorphisms in AKT1, PIK3CA, and mTOR genes are associated with altered BC risk among Iranian women. These findings propose that genetic variants in the PI3K/AKT/mTOR pathway could serve as potential biomarkers for BC susceptibility. Further research with larger cohorts and diverse populations is necessary to confirm these associations.
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