Exploring the Relationship Between MDM4 Gene Polymorphisms (rs1380576 and rs4245739) and Breast Cancer Susceptibility in Bangladesh: A Case-Control Study

Abstract Objectives: Breast cancer (BC) is the most common malignancy among Bangladeshi women. Mouse Double Minute 4 (MDM4) gene polymorphisms have been implicated in BC susceptibility, but data from South Asian populations remain limited. MDM4 is a key negative regulator of the p53 tumor suppressor pathway, and its genetic variants may influence cancer risk through altered p53 signaling. Methods: This case-control study included 112 BC patients from a cancer hospital, Dhaka, Bangladesh, and 124 age- and sex-matched healthy controls (HCs) from the surrounding areas. Genotyping of MDM4 rs1380576 and rs4245739 polymorphisms was performed using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results: Genotype distributions of both polymorphisms conformed to Hardy-Weinberg equilibrium. No significant association was observed for rs4245739 A>C under any genetic model. In contrast, rs1380576 C>G showed a significantly increased BC risk for CC versus GG (aOR = 3.93; 95% CI = 2.09-7.38; p < 0.001) and for CG+CC versus GG (aOR = 2.04; 95% CI = 1.19-3.50; p = 0.009). The recessive model also indicated elevated risk for CC carriers (aOR = 4.58; 95% CI = 2.46-8.55). A strong protective effect was observed for the heterozygous genotype in the over-dominant model (aOR = 0.11; 95% CI = 0.02-0.47; p = 0.003). Conclusion: The MDM4 rs1380576 C>G polymorphism, particularly the CC genotype, is significantly associated with increased BC risk in Bangladeshi women, whereas rs4245739 A>C shows no significant association. These findings suggest rs1380576 may serve as a potential genetic marker for BC susceptibility in this population.