Association of CYP3A5 Genetic Variants With Elevated Breast Cancer Risk: A Case–Control and In Silico Analysis
Sm Faysal BellahBackground
Cytochrome P450 3A5 (CYP3A5) is a key xenobiotic‐metabolizing enzyme that also participates in the biotransformation of endogenous substrates. Functional genetic variation within CYP3A5 can alter enzyme activity and may consequently modify individual susceptibility to malignancy. The contribution of CYP3A5 genetic variation to breast cancer risk, as well as its potential relevance to tumor biology, remains inadequately characterized in the Bangladeshi population.
Objective
The current study investigated the relationship of CYP3A5∗3 (rs776746) polymorphism with the susceptibility of breast cancer and explored its relationship with immune infiltration and survival outcomes.
Methods
The study was conducted as a case–control study including 170 breast cancer patients and 170 age‐matched healthy individuals. CYP3A5∗3 (rs776746) genotypes were determined using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis. Genetic associations were calculated using odds ratios (ORs) with 95% confidence intervals (CIs). Complementary computational analyses evaluated the association of CYP3A5 expression with tumor immune‐cell infiltration using TIMER2.0 and examined its prognostic relevance through survival data from TCGA accessed via UALCAN.
Results
CYP3A5∗3 genotype frequencies differed significantly between cases and controls. Compared with the wild‐type genotype (∗1/∗1), the heterozygote (∗1/∗3) genotype (OR = 2.57; p = 0.0016), mutant homozygote (∗3/∗3) (OR = 1.78; p = 0.0376), and combined variant genotypes (∗1/∗3 + ∗3/∗3) (OR = 2.11; p = 0.0010) were associated with increased breast cancer risk. The CYP3A5∗3 allele was more prevalent in cases than controls (36% vs. 25%; OR = 1.75; p = 0.0009). In silico analysis showed that CYP3A5 expression was positively correlated with immune‐cell infiltration of several immune cells. The elevated expression of CYP3A5 was linked to poorer survival in selected clinical subgroups.
Conclusion
The findings indicate that the CYP3A5∗3 polymorphism may contribute to genetic susceptibility to breast cancer among Bangladeshi women. Additionally, CYP3A5 expression shows a relationship with immune infiltration and may have subgroup‐specific prognostic relevance in breast cancer.