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Background  Breast cancer (BC) is the most prevalent cancer in women and a major public health problem in Morocco. Several Moroccan studies have focused on studying this disease, but more are needed, especially at the genetic and molecular levels. Therefore, we investigated the potential association of several functional germline variants in the genes commonly mutated in sporadic breast cancer.    Methods  In this case–control study, we examined 36 single nucleotide polymorphisms (SNPs) in 13 genes ( APOBEC3A, APOBEC3B, ARID1B, ATR, MAP3K1, MLL2, MLL3, NCOR1, RUNX1, SF3B1, SMAD4, TBX3, TTN ), which were located in the core promoter, 5’-and 3’UTR or which were nonsynonymous SNPs to assess their potential association with inherited predisposition to breast cancer development. Additionally, we identified a ~29.5-kb deletion polymorphism between  APOBEC3A  and  APOBEC3B  and explored possible associations with BC. A total of 226 Moroccan breast cancer cases and 200 matched healthy controls were included in this study.    Results  The analysis showed that12 SNPs in 8 driver genes, 4 SNPs in  APOBEC3B  gene and 1 SNP in  APOBEC3A  gene were associated with BC risk and/or clinical outcome at  P ≤ 0.05  level.  RUNX1 _rs8130963 (odds ratio (OR) = 2.25; 95 % CI 1.42-3.56;  P  = 0.0005; dominant model),  TBX3 _rs8853 (OR = 2.04; 95 % CI 1.38-3.01;  P  = 0.0003; dominant model),  TBX3 _rs1061651 (OR = 2.14; 95 % CI1.43-3.18;  P  = 0.0002; dominant model),  TTN _rs12465459 (OR = 2.02; 95 % confidence interval 1.33-3.07;  P  = 0.0009; dominant model), were the most significantly associated SNPs with BC risk. A strong association with clinical outcome were detected for the genes  SMAD4  _rs3819122 with tumor size (OR = 0.45; 95 % CI 0.25-0.82;  P  = 0.009) and  TTN _rs2244492 with estrogen receptor (OR = 0.45; 95 % CI 0.25-0.82;  P  = 0.009).    Conclusion  Our results suggest that genetic variations in driver and  APOBEC3  genes were associated with the risk of BC and may have impact on clinical outcome. However, the reported association between the deletion polymorphism and BC risk was not confirmed in the Moroccan population. These preliminary findings require replication in larger studies.

Analysis of functional germline variants in APOBEC3 and driver genes on breast cancer risk in Moroccan study population