Association of MDM2 rs2279744 and rs937282 polymorphisms with breast cancer susceptibility and circulating MDM2 and p53 levels in Bangladeshi women: A case-control study
4 affiliations
- 1Research Lab, Rufaida BioMeds, Aftabnagar, Dhaka, Bangladesh
- 2Department of Mathematics and Natural Sciences, BRAC University, Kha 224 Bir Uttam Rafiqul Islam Avenue, Merul Badda, Dhaka, Bangladesh
- 3School of Pharmacy, BRAC University, Kha 224 Bir Uttam Rafiqul Islam Avenue, Merul Badda, Dhaka, Bangladesh
- 4Department of Rheumatology, Bangladesh Medical University, Kazi Nazrul Islam Avenue, Dhaka, Bangladesh
Abstract
Background: The MDM2–p53 signaling pathway plays a central role in tumor suppression, and genetic variants that disrupt this pathway may influence breast cancer (BC) susceptibility. However, data from South Asian populations, particularly Bangladesh, remain limited. Methods: A case–control study was conducted in Bangladeshi women, including BC patients and healthy controls (HCs). Genotyping of MDM2 polymorphisms was performed using PCR-based methods. Circulating MDM2 and p53 protein levels were measured using enzyme-linked immunosorbent assays (ELISA). Associations between genotype, protein levels, BC status, and clinicopathological features were evaluated using appropriate statistical models. Results: Women carrying the heterozygous TG genotype had a markedly increased risk of BC across additive, dominant, and over-dominant models, whereas the GG genotype showed a protective effect under the recessive model. In contrast, rs937282 did not show a significant association with BC risk. Circulating MDM2 levels were significantly elevated in patients compared with controls and varied by rs2279744 genotype, while circulating p53 levels showed an opposite trend. A strong inverse correlation was observed between serum MDM2 and p53 levels, suggesting a potential association with the MDM2–p53 regulatory pathway. Elevated MDM2 levels were also noted in HER2-positive and triple-positive BC subtypes. Conclusion: Together, these findings suggest that the MDM2 rs2279744 polymorphism is associated with breast cancer susceptibility and genotype-specific differences in circulating MDM2 and p53 levels. However, the absence of functional validation limits direct causal inference.
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BibTeX
@article{chowdhury2026association,
title = {{Association of MDM2 rs2279744 and rs937282 polymorphisms with breast cancer susceptibility and circulating MDM2 and p53 levels in Bangladeshi women: A case-control study}},
author = {Mahim Hassan Chowdhury and Farzana Islam and Adiba Ayesha Khan and Md. Ayman Siddique and Nushaiba Binte Hasan and Mahinul Islam Samrat and Mehrin Haque Tanisha and Jarin Tasnim and Samiha Mahjabin and Md. Nazmul Islam and Md. Aminul Haque},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0350622},
url = {https://doi.org/10.1371/journal.pone.0350622},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Association of MDM2 rs2279744 and rs937282 polymorphisms with breast cancer susceptibility and circulating MDM2 and p53 levels in Bangladeshi women: A case-control study
AU - Mahim Hassan Chowdhury
AU - Farzana Islam
AU - Adiba Ayesha Khan
AU - Md. Ayman Siddique
AU - Nushaiba Binte Hasan
AU - Mahinul Islam Samrat
AU - Mehrin Haque Tanisha
AU - Jarin Tasnim
AU - Samiha Mahjabin
AU - Md. Nazmul Islam
AU - Md. Aminul Haque
PY - 2026
DA - 2026/09/01
JO - PLOS One
DO - 10.1371/journal.pone.0350622
UR - https://doi.org/10.1371/journal.pone.0350622
AB - Background: The MDM2–p53 signaling pathway plays a central role in tumor suppression, and genetic variants that disrupt this pathway may influence breast cancer (BC) susceptibility. However, data from South Asian populations, particularly Bangladesh, remain limited. Methods: A case–control study was conducted in Bangladeshi women, including BC patients and healthy controls (HCs). Genotyping of MDM2 polymorphisms was performed using PCR-based methods. Circulating MDM2 and p53 protein levels were measured using enzyme-linked immunosorbent assays (ELISA). Associations between genotype, protein levels, BC status, and clinicopathological features were evaluated using appropriate statistical models. Results: Women carrying the heterozygous TG genotype had a markedly increased risk of BC across additive, dominant, and over-dominant models, whereas the GG genotype showed a protective effect under the recessive model. In contrast, rs937282 did not show a significant association with BC risk. Circulating MDM2 levels were significantly elevated in patients compared with controls and varied by rs2279744 genotype, while circulating p53 levels showed an opposite trend. A strong inverse correlation was observed between serum MDM2 and p53 levels, suggesting a potential association with the MDM2–p53 regulatory pathway. Elevated MDM2 levels were also noted in HER2-positive and triple-positive BC subtypes. Conclusion: Together, these findings suggest that the MDM2 rs2279744 polymorphism is associated with breast cancer susceptibility and genotype-specific differences in circulating MDM2 and p53 levels. However, the absence of functional validation limits direct causal inference.
SN - 1932-6203
ER -