title: Homozygous T172T and Heterozygous G135C Variants of Homologous Recombination Repairing Protein RAD51 are Related to Sporadic Breast Cancer Susceptibility.
abstract: 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.
authors.affiliation: Division of Surgical, Molecular, and Ultrastructural Pathology, Pisa University Hospital, University of Pisa, Pisa, Italy. mszoubi@yu.edu.jo.|Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid, 211-63, Jordan. mszoubi@yu.edu.jo.
authors.forename: Mazhar Salim
authors.initials: MS
authors.lastname: Al-Zoubi
authors.affiliation: Division of Surgical, Molecular, and Ultrastructural Pathology, Pisa University Hospital, University of Pisa, Pisa, Italy.
authors.forename: Chiara Maria
authors.initials: CM
authors.lastname: Mazzanti
authors.affiliation: Division of Surgical, Molecular, and Ultrastructural Pathology, Pisa University Hospital, University of Pisa, Pisa, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Zavaglia
authors.affiliation: Division of Surgical, Molecular, and Ultrastructural Pathology, Pisa University Hospital, University of Pisa, Pisa, Italy.|Department of Pathology and Laboratory Medicine, University of Dammam, Dammam, Saudi Arabia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al Hamad
authors.affiliation: Division of Surgical, Molecular, and Ultrastructural Pathology, Pisa University Hospital, University of Pisa, Pisa, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Armogida
authors.affiliation: 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.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.affiliation: Division of Surgical, Molecular, and Ultrastructural Pathology, Pisa University Hospital, University of Pisa, Pisa, Italy.
authors.forename: Generoso
authors.initials: G
authors.lastname: Bevilacqua
mesh_terms: D020121:5' Untranslated Regions; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D059765:Homologous Recombination; D006720:Homozygote; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D051135:Rad51 Recombinase / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; C495153:RAD51 protein, human; D051135:Rad51 Recombinase
keywords: 135 G>C; Breast cancer; RAD51; SNP; T172T; UTR-5′