Title: Impact of CYP3A5*3 genetic polymorphism on breast cancer risk: Evidence from Bangladesh.

[BACKGROUND] The CYP3A5 gene plays a crucial role in drug metabolism and carcinogen activation, potentially influencing breast cancer susceptibility. However, its genetic association with breast cancer risk in the Bangladeshi population remains under explored.

[OBJECTIVE] This study aims to examine the expression and genetic correlation of the CYP3A5*3 (rs776746) polymorphism in relation to breast cancer susceptibility.

[METHODS] A case-control study was performed with 150 breast cancer patients and 150 healthy controls to investigate genotypic variations of the CYP3A5*3 (rs776746) polymorphism using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis. The relationship between the CYP3A5*3 variant and breast cancer risk was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs) through logistic regression models.

[RESULTS] The CYP3A5*3 polymorphism exhibited a significant association with increased breast cancer risks. Breast cancer risk was found to be higher in heterozygotes than in homozygotes. Individuals carrying the heterozygous (*1/*3) and mutant homozygote (*3/*3) genotypes had a 3.04-fold (p = 0.0005) and 1.9-fold (p = 0.0227) increased risk of developing breast cancer respectively. Furthermore, the combined (*1/*3 + *3/*3) genotype was significantly linked to a 3.67-fold higher susceptibility to breast cancer risks (p < 0.0005).

[CONCLUSION] Our findings suggest that the CYP3A5*3 polymorphism is significantly associated with an elevated risk of breast cancer in Bangladeshi population.