Polymorphisms and mutations in GSTP1, RAD51, XRCC1 and XRCC3 genes in breast cancer patients.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Pisa - Italy.|Department of Biological Sciences, Yarmouk University, Irbid - Jordan.
Mazhar Salim
MS
Al Zoubi
Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Pisa - Italy.
Katia
K
Zavaglia
Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Pisa - Italy.
Chiara
C
Mazanti
Department of Pathology, Faculty of Medicine, University of Dammam, Dammam - Kingdom of Saudi Arabia.
Mohammad
M
Al Hamad
Department of Biological Sciences, Yarmouk University, Irbid - Jordan.
Khalid
K
Al Batayneh
Department of Biological Sciences, Yarmouk University, Irbid - Jordan.
Alaa A A
AAA
Aljabali
Department of Translational Research and New Surgical and Medical Technologies, University of Pisa, Pisa - Italy.
Generoso
G
Bevilacqua
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D051135:Rad51 Recombinase / Q000235:genetics*; D000076105:X-ray Repair Cross Complementing Protein 1 / Q000235:genetics*
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; C495153:RAD51 protein, human; D051135:Rad51 Recombinase