Homozygous T172T and Heterozygous G135C Variants of Homologous Recombination Repairing Protein RAD51 are Related to Sporadic Breast Cancer Susceptibility

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• 作者：Mazhar Salim Al-Zoubi ; Chiara Maria Mazzanti ; Katia Zavaglia…
• 关键词：RAD51 ; UTR ; 5′
135 G> ; C ; T172T ; Breast cancer ; SNP
• 刊名：Biochemical Genetics
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：54
• 期：1
• 页码：83-94
• 全文大小：1,200 KB
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• 作者单位：Mazhar Salim Al-Zoubi (1) (2)
  Chiara Maria Mazzanti (1)
  Katia Zavaglia (1)
  Mohammad Al Hamad (1) (4)
  Ivana Armogida (1)
  Michael P. Lisanti (3)
  Generoso Bevilacqua (1)
  
  1. Division of Surgical, Molecular, and Ultrastructural Pathology, Pisa University Hospital, University of Pisa, Pisa, Italy
  2. Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid, 211-63, Jordan
  4. Department of Pathology and Laboratory Medicine, University of Dammam, Dammam, Saudi Arabia
  3. Manchester Breast Centre & Breakthrough Breast Cancer Research Unit, Paterson Institute for Cancer Research, Manchester Academic Health Science Centre, School of Cancer, Enabling Sciences and Technology, University of Manchester, Manchester, UK
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Human Genetics
  Biochemistry
  Zoology
  Medical Microbiology
  
• 出版者：Springer Netherlands
• ISSN：1573-4927

文摘

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. Keywords RAD51 UTR-5′ 135 G>C T172T Breast cancer SNP