Abstract
BackgroundBreast 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.MethodsIn 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.ResultsThe 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).ConclusionOur 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.
Highlights
Breast cancer (BC) is the most prevalent cancer in women and a major public health problem in Morocco
12 single nucleotide polymorphisms (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 (Tables 2 and 3)
No statistically significant association was observed between APOBEC3 deletion and breast cancer risk (Table 5). In this population-based case–control study, we investigated for the first time the influence of the germline variation and copy number variations (CNVs) in the potential driver genes and APOBEC3 genes on breast cancer susceptibility in a North African population
Summary
Breast cancer (BC) is the most prevalent cancer in women and a major public health problem in Morocco. Breast Cancer (BC) is one of the most frequent malignant disease and primary cause of death in women worldwide. Recent genome-wide association studies (GWASs) focusing on evaluating common single nucleotide polymorphisms (SNPs) have identified more than 70 genetic susceptibility loci for breast cancer [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25]. Genome sequencing has revealed that many cancers, including breast cancer, have somatic mutation spectra dominated by C-to-T transitions
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