APOBEC3A/B deletion hybrid encodes a cytidine deaminase with dual antiviral and mutagenic functions. The protein catalyzes deamination of cytosine and methylcytosine in single-stranded DNA, targeting foreign genetic elements including viruses and retrotransposons 1. A common 30 kb deletion affecting APOBEC3A and APOBEC3B genes creates a fusion protein with altered activity patterns. At the mechanistic level, APOBEC3A/B induces DNA replication stress by generating single-stranded DNA gaps through PrimPol-mediated repriming, which are subsequently repaired by ATR, RAD51, and translesion synthesis pathways 1. The enzyme generates characteristic APOBEC-associated mutational signatures (SBS2 and SBS13) observed across multiple cancer types and viral infections 2. Clinically, the APOBEC3A/B deletion polymorphism shows complex disease associations. The deletion is associated with reduced endometrial cancer risk, particularly in women aged 50-60 years 3, and exhibits age-dependent effects for lung cancer, with increased risk in individuals under 50 years 4. However, the polymorphism shows no association with HPV infection or cervical carcinogenesis 5. Notably, APOBEC-driven mutagenesis contributes to tumor heterogeneity and evolution, shaping clonal dynamics differently in early versus late cancer stages 6. The presence of APOBEC3A/B deletion combined with viral infection (MMTV-like) predisposes to early-onset breast cancer 7.