Browsing by Author "Gonzalez-Hormazabal, Patricio"

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    A Single Variant in Pri-miRNA-155 Associated with Susceptibility to Hereditary Breast Cancer Promotes Aggressiveness in Breast Cancer Cells
    (2022) Landeros, Natalia; Gonzalez-Hormazabal, Patricio; Perez-Moreno, Pablo; Tapia, Julio C.; Jara, Lilian
    Variants in genes encoding for microRNAs have been associated with their deregulation in breast cancer (BC). Sequencing of microRNAs deregulated in BC was performed using DNA from Chilean patients with a strong family history and negative for mutations in BRCA1/BRCA2. Seventeen variants were identified, three of which were selected for a case-control association study: rs376491654 (miR-335), rs755634302 (miR-497), and rs190708267 (miR-155). For rs190708267 C>T, the heterozygous T allele was detected in four BC cases and absent in controls, while homozygous TT cases were not detected. Variants were modelled in silico, cloned in a plasmid, expressed in BC cell lines, and functional in vitro assays were performed. Overexpression of the miR-155-T allele increased mature miR-155-5p levels in both BC cell lines, suggesting that its presence alters pre-miR-155 processing. Moreover, BC cells overexpressing the miR-155-T allele showed increased proliferation, migration, and resistance to cisplatin-induced death compared to miR-155-C overexpressing cells. Of note, the 3 ' UTR of APC, GSK3 beta, and PPP1CA genes, all into the canonical Wnt signaling pathway, were identified as direct targets. APC and GSK3 beta mRNA levels decreased while PP1 levels increased. These results suggest a pathogenic role of the variant rs190708267 (miR-155) in BRCA 1/2 negative BC, conferring susceptibility and promoting traits of aggressiveness.
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    Prevalence of Helicobacter pylori Antimicrobial Resistance Among Chilean Patients
    (2021) Gonzalez-Hormazabal, Patricio; Arenas, Alex; Serrano, Carolina; Pizarro, Margarita; Fuentes-Lopez, Eduardo; Arnold, Jorge; Berger, Zoltan; Musleh, Maher; Valladares, Hector; Lanzarini, Enrique; Jara, Lilian; Castro, V. Gonzalo; Camargo, M. Constanza; Riquelme, Arnoldo
    Background. Treatments for Helicobacter pylori (H. pylori) eradication include the use of antibiotics and a proton-pump inhibitor. Antibiotic resistance is a major concern for two drugs: levofloxacin and clarithromycin. The aim was to determine the prevalence of levofloxacin resistance (LevoR) and clarithromycin resistance (ClaR) in an urban population in Santiago, Chile.
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    The BARD1 Cys557Ser variant and risk of familial breast cancer in a South-American population
    (2012) Gonzalez-Hormazabal, Patricio; Reyes, José M.; Blanco, Rafael; Bravo, Teresa; Carrera, Ignacio; Peralta, Octavio; Gómez, Fernando; Waugh, Enrique; Margarit, Sonia; Ibañez, Gladys; Santos Martín, José Luis; Jara, Lilian
    Since the discovery of the BRCA1 and BRCA2 genes, much work has been carried out to identify further breast cancer (BC) susceptibility genes. BARD1 (BRCA1-associated ring domain) was originally identified as a BRCA1-interacting protein but has also been described in tumor-suppressive functions independent of BRCA1. Some association studies have suggested that the BARD1 Cys557Ser variant might be associated with increased risk of BC, but others have failed to confirm this finding. To date, this variant has not been analyzed in Spanish or South-American populations. In this study, using a case-control design, we analyzed the C-terminal Cys557Ser change in 322 Chilean BC cases with no mutations in BRCA1 or BRCA2 and in 570 controls in order to evaluate its possible association with BC susceptibility. BARD1 Cys557Ser was associated with an increased BC risk (P = 0.04, OR = 3.4 [95 % CI 1.2-10.2]) among cases belonging to families with a strong family history of BC. No difference between single cases affected with age < 50 years at diagnosis (n = 117) and controls was observed for carriers of Cys/Ser genotype. It is likely that this variant is not involved in BC risk in this group of women. We also analyzed a possible interaction between BARD1 557Ser/XRCC3 241Met variants considering the role of both genes in the maintenance of genome integrity. The combined genotype Cys/Ser-carrier with the XRCC3 241Met allele was associated with an increased BC risk (P = 0.02, OR = 5.01 [95 % CI 1.36-18.5]) among women belonging to families with at least three BC and/or ovarian cancer cases. Our results suggest that BARD1 557Ser and XRCC3 241Met may play roles in BC risk in women with a strong family history of BC. Nevertheless there is no evidence of an interaction between the two SNPs. These findings should be confirmed by other studies and in other populations.