Polymorphisms and mutations in GSTP1, RAD51, XRCC1 and XRCC3 genes in breast cancer patients
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Article Type: ORIGINAL RESEARCH ARTICLE
AuthorsMazhar Salim Al Zoubi, Katia Zavaglia, Chiara Mazanti, Mohammad Al Hamad, Khalid Al Batayneh, Alaa A.A. Aljabali, Generoso Bevilacqua
Genotoxic factors, including ionizing radiation and oxidative stress, are associated with genomic instability and development of breast cancer (BC). The homologous recombination DNA repair (HRR) pathway, base excision repair (BER) mechanism, and antioxidative enzymes are required as defense mechanisms against these DNA damaging agents. GSTP1, XRCC1, XRCC3 and RAD51 proteins are essential components of antioxidation, BER and HRR of DNA, respectively. Deficiencies in BER, HRR and antioxidation pathways are involved in the progression of cancer.
Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue and blood samples of BC patients of an Italian population. Genomic DNA was also extracted from blood specimens of a control group. DNA sequencing was performed for six single-nucleotide polymorphisms (SNPs) in the GSTP1, RAD51, XRCC1 and XRCC3 genes in BC patients and the control group.
Two variants in the 5’-UTR of the XRCC3 (rs1799794 A/G) and RAD51 (rs1801321) genes showed a significant association with susceptibility to BC (OR = 4.125; 95% CI 1.057-16.102; p = 0.03 and OR = 2.04; 95% CI 0.4925-8.449; p = 0.007, respectively). Additionally, we reported 2 mutations in intron 7 of the XRCC3 gene, CTdel (rs543072564) and A/G (rs369703243).
Our results underscored the existence of an association between XRCC3-5’-UTR-A/G (rs1799794) and RAD51-5’-UTR G172T (rs1801321) genotypes and BC risk in an Italian population. The presence of mutations in the intronic region of the XRCC3 gene highlights the importance of more sequence screening of DNA repair genes for possible genetic penetrance in BC.
- • Received on 28/11/2016
- • Accepted on 15/02/2017
- • Available online on 06/03/2017
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- Al Zoubi, Mazhar Salim [PubMed] [Google Scholar] 1, 2, * Corresponding Author (firstname.lastname@example.org)
- Zavaglia, Katia [PubMed] [Google Scholar] 1
- Mazanti, Chiara [PubMed] [Google Scholar] 1
- Al Hamad, Mohammad [PubMed] [Google Scholar] 3
- Al Batayneh, Khalid [PubMed] [Google Scholar] 2
- Aljabali, Alaa A.A. [PubMed] [Google Scholar] 2
- Bevilacqua, Generoso [PubMed] [Google Scholar] 1
Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Pisa - Italy
Department of Biological Sciences, Yarmouk University, Irbid - Jordan
Department of Pathology, Faculty of Medicine, University of Dammam, Dammam - Kingdom of Saudi Arabia