PloS one · 2026
Association of MDM2 rs2279744 and rs937282 polymorphisms with breast cancer susceptibility and circulating MDM2 and p53 levels in Bangladeshi women: A case-control study.
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Chowdhury Mahim Hassan, Islam Farzana, Khan Adiba Ayesha, Siddique Md Ayman, Hasan Nushaiba Binte, Samrat Mahinul Islam, Tanisha Mehrin Haque, Tasnim Jarin, Mahjabin Samiha, Islam Md Nazmul, Haque Md Aminul
Аннотация
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.
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.