Al-Zoubi Mazhar Salim, Mazzanti Chiara Maria, Zavaglia Katia, Al Hamad Mohammad, Armogida Ivana, Lisanti Michael P, Bevilacqua Generoso
Division of Surgical, Molecular, and Ultrastructural Pathology, Pisa University Hospital, University of Pisa, Pisa, Italy.
Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid, 211-63, Jordan.
Biochem Genet. 2016 Feb;54(1):83-94. doi: 10.1007/s10528-015-9703-z. Epub 2015 Dec 9.
Breast cancer (BC) is the most common cancer and the second leading cause of death among women worldwide. Only 10% of BC cases have been related to genetic predisposition. Rad51, a homologous recombination (HR) protein plays an important role in HR in meiosis and repairing DNA double-strand breaks. Expression of RAD51 may be a predictive biomarker in certain types of cancers. The exact mechanisms involved in the regulation of RAD51 expression are not fully understood, but certain transcription factors have been suggested to be the tuning mechanism of its expression. In this study, we propose that polymorphisms in the 5'-UTR promoter region of the RAD51 gene are prognostic factors for BC development. Direct sequencing of 106 samples from sporadic BC patients and 54 samples from a control group was performed. FFPE samples were the choice of sample collection, which might be a limitation of our study. Homologous variant T172T alone was found to be significantly associated with BC risk (OR 3.717, 95% CI 2.283-6.052, p < 0.0001). On the other hand, heterozygous G135C did not show any significant relationship with risk of sporadic BC (OR 1.598, 95% CI 0.5638-4.528, p > 0.05). Moreover, both variants; homozygous T172T and heterozygous G135C together; showed a significant relationship with sporadic BC susceptibility.
乳腺癌（BC）是全球女性中最常见的癌症，也是第二大死因。只有10%的乳腺癌病例与遗传易感性有关。Rad51是一种同源重组（HR）蛋白，在减数分裂中的HR和修复DNA双链断裂中起重要作用。RAD51的表达可能是某些类型癌症的预测生物标志物。RAD51表达调控的确切机制尚未完全了解，但某些转录因子被认为是其表达的调节机制。在本研究中，我们提出RAD51基因5'-UTR启动子区域的多态性是乳腺癌发生的预后因素。对106例散发性乳腺癌患者的样本和54例对照组样本进行了直接测序。FFPE样本是样本采集的选择，这可能是我们研究的一个局限性。单独发现同源变体T172T与乳腺癌风险显著相关（OR 3.717，95%CI 2.283-6.052，p<0.0001）。另一方面，杂合子G135C与散发性乳腺癌风险没有任何显著关系（OR 1.598，95%CI 0.5638-4.528，p>0.05）。此外，两种变体；纯合子T172T和杂合子G135C一起；与散发性乳腺癌易感性显著相关。
