Laboratory of Physiology, Genetics and Ethnopharmacology, Department of Biology, Faculty of Sciences, University of Mohammed First, Oujda, Morocco.
Oncology Center Mohamed VI Ibn Rochd, Casablanca, Morocco.
BMC Cancer. 2018 Mar 15;18(1):292. doi: 10.1186/s12885-018-4214-z.
Genetic determinants of breast cancer (BC) remained largely unknown in the majority of Moroccan patients. The purpose of this study was to explore the association of ERCC2 and MTHFR polymorphisms with genetic susceptibility to breast cancer in Moroccan population.
We genotyped ERCC2 polymorphisms (rs1799793 (G934A) and rs13181 (A2251C)) and MTHFR polymorphisms (rs1801133 (C677T) and rs1801131 (A1298C)) using TaqMan SNP Genotyping Assays. Genotypes were compared in 151 BC cases and 156 population-matched controls. Allelic, genotypic and haplotype associations with the risk and clinicopathological features of BC were assessed using logistic regression analyses.
ERCC2-rs1799793-AA genotype was associated with high risk of BC compared to wild type genotype (recessive model: OR: 2.90, 95% CI: 1.34-6.26, p = 0.0069) even after Bonferroni correction (p < 0,0125). MTHFR rs1801133-TT genotype was associated with increased risk of BC (recessive model, OR: 2.49, 95% CI: 1.17-5.29, p = 0.017) but the association turned insignificant after Bonferroni correction. For the rest of SNPs, no statistical associations to BC risk were detected. Significant association with clinical features was detected for MTHFR-rs1801133-TC genotype with early age at diagnosis and familial BC. Following Bonferroni correction, only association with familial BC remained significant. MTHFR-rs1801131-CC genotype was associated with sporadic BC. ERCC2-rs1799793-AA genotype correlated with ER+ and PR+ breast cancer. ERCC2-rs13181-CA genotype was significantly associated large tumors (T ≥ 3) in BC patients. None of these associations passed Bonferroni correction. Haplotype analysis showed that ERCC2 A-C haplotype was significantly associated with increased BC risk (OR: 3.71, 95% CI: 1.7-8.12, p = 0.0002 and p = 0.0008 before and after Bonferroni correction, respectively) and positive expression of ER and PR in BC patients. ERCC2 G-C haplotype was correlated with PR negative and larger tumor (T4). We did not find any MTHFR haplotypes associated with BC susceptibility. However, the less common haplotype MTHFR T-C was more frequent in young patients and in familial breast cancer, while MTHFR C-C haplotype was associated with sporadic BC form.
Our findings are a first observation of association between ERCC2 SNPs and breast cancer in Moroccan population. The results suggested that ERCC2 and MTHFR polymorphisms may be reliable for assessing risk and prognosis of BC in Moroccan population.
在大多数摩洛哥患者中，乳腺癌（BC）的遗传决定因素在很大程度上仍未知。本研究的目的是探讨 ERCC2 和 MTHFR 多态性与摩洛哥人群中乳腺癌遗传易感性的关系。
我们使用 TaqMan SNP 基因分型检测法对 ERCC2 多态性（rs1799793（G934A）和 rs13181（A2251C））和 MTHFR 多态性（rs1801133（C677T）和 rs1801131（A1298C））进行基因分型。在 151 例 BC 病例和 156 例人群匹配对照中比较基因型。使用逻辑回归分析评估等位基因、基因型和单倍型与 BC 风险和临床病理特征的关联。
与野生型基因型相比，ERCC2-rs1799793-AA 基因型与 BC 的高风险相关（隐性模型：OR：2.90，95%CI：1.34-6.26，p=0.0069），即使经过 Bonferroni 校正（p<0.0125）。MTHFR rs1801133-TT 基因型与 BC 风险增加相关（隐性模型，OR：2.49，95%CI：1.17-5.29，p=0.017），但经过 Bonferroni 校正后，该关联变得不显著。对于其余的 SNPs，未检测到与 BC 风险相关的统计学关联。MTHFR-rs1801133-TC 基因型与发病年龄较早和家族性 BC 显著相关。经过 Bonferroni 校正后，只有家族性 BC 的关联仍然显著。MTHFR-rs1801131-CC 基因型与散发性 BC 相关。ERCC2-rs1799793-AA 基因型与 ER+和 PR+乳腺癌相关。ERCC2-rs13181-CA 基因型与 BC 患者的大肿瘤（T≥3）显著相关。这些关联均未通过 Bonferroni 校正。单倍型分析表明，ERCC2 A-C 单倍型与 BC 风险增加显著相关（OR：3.71，95%CI：1.7-8.12，p=0.0002 和 p=0.0008，分别在 Bonferroni 校正之前和之后），并与 BC 患者 ER 和 PR 的阳性表达相关。ERCC2 G-C 单倍型与 PR 阴性和较大肿瘤（T4）相关。我们没有发现任何与 BC 易感性相关的 MTHFR 单倍型。然而，不太常见的单倍型 MTHFR T-C 在年轻患者和家族性乳腺癌中更为常见，而 MTHFR C-C 单倍型与散发性 BC 形式相关。
我们的研究结果首次观察到 ERCC2 SNPs 与摩洛哥人群中乳腺癌之间的关联。结果表明，ERCC2 和 MTHFR 多态性可能可用于评估摩洛哥人群中 BC 的风险和预后。
