Marouf Chaymaa, Göhler Stella, Filho Miguel Inacio Da Silva, Hajji Omar, Hemminki Kari, Nadifi Sellama, Försti Asta
Department of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Laboratory of Genetics and Molecular Pathology-Medical School of Casablanca, Casablanca, Morocco.
BMC Cancer. 2016 Feb 26;16:165. doi: 10.1186/s12885-016-2210-8.
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.
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.
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).
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.
乳腺癌（BC）是女性中最常见的癌症，也是摩洛哥的一个主要公共卫生问题。摩洛哥的多项研究都聚焦于对这种疾病的研究，但仍需要更多研究，尤其是在基因和分子层面。因此，我们调查了散发性乳腺癌中常见突变基因的几种功能性种系变异的潜在关联。
在这项病例对照研究中，我们检测了13个基因（APOBEC3A、APOBEC3B、ARID1B、ATR、MAP3K1、MLL2、MLL3、NCOR1、RUNX1、SF3B1、SMAD4、TBX3、TTN）中的36个单核苷酸多态性（SNP），这些SNP位于核心启动子、5'和3'非翻译区或为非同义SNP，以评估它们与乳腺癌发生遗传易感性的潜在关联。此外，我们鉴定了APOBEC3A和APOBEC3B之间约29.5 kb的缺失多态性，并探讨了其与乳腺癌的可能关联。本研究共纳入226例摩洛哥乳腺癌病例和200例匹配的健康对照。
分析表明，8个驱动基因中的12个SNP、APOBEC3B基因中的4个SNP和APOBEC3A基因中的1个SNP在P≤0.05水平与乳腺癌风险和/或临床结局相关。RUNX1_rs8130963（优势比（OR）=2.25；95%置信区间1.42 - 3.56；P = 0.0005；显性模型）、TBX3_rs
