ISABELA BARBOSA FIRIGATO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/40 - Laboratório de Imunohematologia e Hematologia Forense, Hospital das Clínicas, Faculdade de Medicina
LIM/40 - Laboratório de Imunohematologia e Hematologia Forense, Hospital das Clínicas, Faculdade de Medicina
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- Many hands make light work: CNV of GSTM1 effect on the oral carcinoma risk(2022) FIRIGATO, Isabela; LOPEZ, Rossana V. M.; CURIONI, Otavio A.; ANTONIO, Juliana De; GATTAS, Gilka Figaro; GONCALVES, Fernanda de ToledoBackground: Genetic alterations of oral squamous cell carcinoma (OSCC) allow the understanding of the oral carcinogenesis and the identification of molecular biomarkers that aid the early diagnosis of the disease. The copy number variation (CNV) of GSTM1 and GSTT1 are promising targets because these two genes codify enzymes that perform the inactivation of tobacco carcinogens, which are the main risk factor of OSCC. However, the different levels of - detoxification mechanism in relation to each copy of the genes are unknown. Therefore, this study aimed to investigate the possible association of the CNV of GSTM1 and GSTT1 with the risk of development of OSCC. Methods: A total of 234 OSCC patients and 422 patients without any cancer diagnoses were recruited from Heli acute accent opolis Hospital from 2000 to 2011. The CNV was determined by TaqMan real-time PCR and the CopyCaller software. Odds ratio (OR) and 95% confidence interval (95% CI) values were calculated by Multiple Logistic Regression. Results: Most OSCC patients reported they continued smoking high amounts of cigarettes despite the tumor diagnosis. The CNV of GSTM1 varied from zero to two copies and the analysis revealed that two copies of GSTM1 decreased by 53% the OSCC risk (OR 0.47; 95% CI 0.24-0.92) and the risk of the tumor was modified according to the interaction of the CNV of GSTM1 and the cigarette smoking consumption, which for the amount of 40 packs-year of cigarettes the OSCC risk diminished progressively according to the increase of copies of GSTM1. Although the GSTT1 gene varied from zero to three copies, none of them were associated with the tumor risk. Conclusion: The findings suggest that the CNV of GSTM1 might be applied as a tool for the surveillance of patients and the early detection of OSCC.
- Polymorphisms of CHRNA3 and CHRNA5: Head and neck cancer and cigarette consumption intensity in a Brazilian population(2019) SILVA, Mariana R.; GATTAS, Gilka J. F.; ANTONIO, Juliana De; FIRIGATO, Isabela; CURIONI, Otavio A.; GONCALVES, Fernanda de ToledoBackground: Cigarette consumption has been identified as the main non-etiological factor in head and neck cancer (HNC) development. One of the main compounds in cigarettes is nicotine, which binds directly to nicotine acetylcholine receptors (nAchRs) in the body, which are encoded by different genes of the CHRNA family. Polymorphisms in some of these genes have been studied in relation to the risk of HNC and cigarette consumption intensity. The aim of this study was to evaluate whether there were associations between the CHRNA3 (rs578776) and CHRNA5 (rs16969968) polymorphisms and HNC risk and between the polymorphisms and the intensity of cigarette consumption. Methods: A total of 1,067 individuals from Heliopolis Hospital in Sao Paulo were investigated, including 619 patients with HNC and 448 patients without diagnosed tumors. All participants answered a questionnaire about sociodemographic information and cigarette consumption data. The polymorphisms were determined by TaqMan genotyping by real-time PCR. Results: The polymorphisms studied, rs578776 (CHRNA3) and rs16969968 (CHRNA5), did not have an association with HNC risk, but the rs16969968 homozygous genotype was associated with increased cigarette consumption intensity (OR 1.93, 95% CI 1.05-3.58). Conclusion: The polymorphism CHRNA5 can be considered an indirect risk factor for neoplasms in these Brazilian samples when cigarette consumption increased.
- How many copies of GSTM1 and GSTT1 are associated with head and neck cancer risk?(2019) FIRIGATO, Isabela; GONCALVES, Fernanda de Toledo; ANTONIO, Juliana De; CURIONI, Otavio Alberto; SILVA, Mariana Rocha; GATTAS, Gilka Jorge FigaroPurpose: GSTM1 and GSTT1 present a polymorphism that can drive complete gene deletions. The current methodology can powerfully determine GSTM1 and GSTT1 copy number variations (CNVs), which may clarify the real contribution of each gene copies to the cellular detoxification process and tumour risk. However, only analysing the presence/absence of these genes yielded controversial results for several disorders, including cancer. Because head and neck cancer (HNC) is becoming a serious global health problem, this study determined the CNVs of GSTM1 and GSTT1 in an HNC case-control population and investigated the possible association between gene copy numbers and tumour risk. Methods: CNV was evaluated by (Ct) 2(-Delta Delta Ct) qPCR methodology in 619 HNC patients and 448 patients with no tumour diagnosis. Results: The genes copy number range was 0-3. The CNV of GSTM1 and GSTT1 frequencies were similar between the cases and control. Thus, none copy of GSTM1 and GSTT1 were associated with HNC risk. Notwithstanding, one copy of both genes had higher frequencies among individuals who carried GSTM1 and GSTT1. Conclusions: One copy number of GSTM1 and GSTT1 presented a higher frequency among carrier genes, but the CNV of GSTM1 and GSTT1 was not associated with HNC risk.
- The copy number variation of GSTM1 as a promising prognostic factor of oral squamous cell carcinoma(2022) FIRIGATO, Isabela; LOPEZ, Rossana V. M.; CURIONI, Otavio A.; ANTONIO, Juliana De; GATTAS, Gilka J. F.; GONCALVES, Fernanda de ToledoObjective. The aim of this study was to investigate whether the copy number variation (CNV) of GSTM1 and GSTT1 is related to the occurrence of oral squamous cell carcinoma (OSCC) relapses, along the overall and progression-free survival of patients. Study Design. A total of 234 OSCC patients were recruited from the Heliopolis hospital and they were distributed among 4 groups according to the occurrence of OSCC relapses. Fisher exact test, odds ratio (OR), and 95% CI were determined to investigate the chances of OSCC progression. The overall and progression-free survival were analyzed by the Kaplan-Meier and Cox regression methods. Results. The CNV of GSTM1 analysis showed that one copy of the gene was associated with reduced chances of OSCC recurrences (OR 0.45; 95% CI 0.25-0.81) and decreased the risk of tumor progression (HR 0.50; 95% CI 0.33-0.75). Furthermore, one copy of GSTM1 was related to a better overall survival rate (HR 0.63; 95% CI 0.0.44-0.91). Regarding the CNV of GSTT1, no copies were associated with the chances of OSCC relapses, the overall survival, or the progression-free survival. Conclusions. The CNV of GSTM1 may be applied to predict OSCC relapses and aid the treatment management, which might improve the survival rates of patients.