Impact of functional germline variants and a deletion polymorphism in APOBEC3A and APOBEC3B on breast cancer risk and survival in a Swedish study population

Abstract

Purpose: The C → T mutation signature caused by APOBEC family members contributes to the development of breast cancer (BC). Also overexpression of APOBEC3B and a ~29.5-kb deletion polymorphism between APOBEC3A and APOBEC3B have been associated with increased BC risk.

Methods: We investigated in a population-based study, with 782 Swedish BC cases and 1559 controls, associations between potentially functional germline variants in APOBEC3A or APOBEC3B gene and BC risk and survival. Additionally, we identified deletion polymorphism carriers and explored possible associations with BC.

Results: No evidence of association between any germline variant, including the deletion polymorphism, and BC risk or survival was observed. Only APOBEC3A promoter polymorphism rs5757402 was associated with low stage (OR = 0.69, 95 % CI 0.50-0.96, dominant model).

Conclusion: The reported association between the deletion polymorphism and BC risk was not confirmed in the Swedish population, nor did any genotyped germline variant show any association with BC risk or survival.

Keywords: APOBEC3; Breast cancer; Deletion polymorphism; Germline variants; Single-nucleotide polymorphism.

Fig. 1

Linkage disequilibrium display of APOBEC3A and APOBEC3B with selected functional SNPs and the deletion polymorphism showing r2 values and SNPs affected by the deletion polymorphism. Genotyped SNPs are marked with red boxes. Pairwise linkage disequilibrium r2 colour scheme with white = 0 and black = 1. Figure originates from HaploView^® with SNP data from 1000 genomes (phase 3)