Department of Pathology, Farhat Hached Hospital, Sousse, Tunisia.
Cancer Epidemiol. 2012 Apr;36(2):190-7. doi: 10.1016/j.canep.2011.09.001. Epub 2011 Oct 5.
The aim of this study was to evaluate the contribution of the BRCA1 and BRCA2 promoter methylation in the pathogenesis of sporadic breast cancer in Tunisian patients.
Breast carcinoma tissues (n=117) and available paired normal breast tissues (n=65) from Tunisian women who had no family history were investigated for the methylation status of BRCA1 and BRCA2 promoters using methylation-specific PCR. Breast specimens from women without carcinoma (16 fibroadenomas and 5 mastopathies) were used as control.
Hypermethylation of BRCA1 and BRCA2 promoters was detected respectively in 60.7% and 69.2% of the carcinoma tissues, and in only 7.7% and 4.6% of the paired normal breast tissues. None of the fibroadenomas and mastopathies showed hypermethylation. Correlations were found between BRCA1 and BRCA2 hypermethylation and decrease in their mRNA expression (p=0.02 and p=0.009, respectively). Moreover, BRCA1 methylation correlates with patients age (p=0.01) and triple negative (ER-, PR-, HER2-) tumors (p=0.01). Patients with methylated BRCA1 and/or BRCA2 had a significant prolonged survivals compared to those with unmethylated tumors (p=0.002).
Our results suggest an important role of BRCA1 and BRCA2 promoter methylation in breast cancer development in the Tunisian population.
本研究旨在评估 BRCA1 和 BRCA2 启动子甲基化在突尼斯散发性乳腺癌发病机制中的作用。
对 117 例无家族史的突尼斯女性乳腺癌组织和 65 例可获得的配对正常乳腺组织进行 BRCA1 和 BRCA2 启动子甲基化状态的检测，采用甲基化特异性 PCR。将无癌女性（16 例纤维腺瘤和 5 例乳腺病）的乳腺标本作为对照。
BRCA1 和 BRCA2 启动子的高甲基化分别在 60.7%和 69.2%的癌组织中检测到，而在仅 7.7%和 4.6%的配对正常乳腺组织中检测到。纤维腺瘤和乳腺病均未显示高甲基化。BRCA1 和 BRCA2 高甲基化与它们的 mRNA 表达降低之间存在相关性（p=0.02 和 p=0.009，分别）。此外，BRCA1 甲基化与患者年龄（p=0.01）和三阴性（ER-、PR-、HER2-）肿瘤（p=0.01）相关。与未甲基化肿瘤相比，甲基化的 BRCA1 和/或 BRCA2 患者的生存时间显著延长（p=0.002）。
我们的结果表明，BRCA1 和 BRCA2 启动子甲基化在突尼斯人群乳腺癌的发展中起着重要作用。
