RESUMO
Codon 72 polymorphism of the tumor suppressor gene TP53 has been associated with a higher risk in the development of several types of cancer. The polymorphism results in a variant protein with either an arginine (CGC) or a proline residue (CCC). The aim of this study was to analyze the association of the TP53 codon 72 polymorphism with the risk of developing gastric cancer in a high-risk population from the central-western region of Venezuela. DNA was extracted from paraffin-embedded gastric adenocarcinoma biopsies (n=65) and endoscopic biopsies from chronic gastritis patients (n=87). TP53 codon 72 polymorphism was determined by PCR-RFLP from all samples. Patients with gastric cancer had a significantly higher frequency (P = 0.037) of the Arg allele than those with chronic gastritis. A logistic regression analysis suggested that Arg carrier individuals had a 4.6-fold higher risk (95% CI 1.0-21.3) of developing gastric cancer. An increment of the Arg/Arg genotype was observed in poor-differentiated gastric adenocarcinoma (OR: 3.1; 95% CI 1.0-9.2), and of the Arg/Pro genotype in well/moderate-differentiated adenocarcinoma samples (OR: 3.5; 95% CI 1.1-11.0), when comparing within the gastric cancer samples; and the last group also when contrasting it with chronic gastritis patients (OR: 2.4; 95% CI 1.1-5.2). The results of this study suggest that the carriage of the Arg allele could be associated with the development of gastric cancer in this Venezuelan population.
Assuntos
Adenocarcinoma/genética , Códon/genética , Genes p53 , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Diferenciação Celular , DNA de Neoplasias/genética , Feminino , Gastrite/epidemiologia , Gastrite/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Venezuela/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Genetic predisposition may play a role in the prevalence of gastric cancer (GC). AIM: To investigate the relationship between selected interleukin-1 (IL-1) loci polymorphisms and gastric cancer risk in the Central-Western region of Venezuela, where gastric cancer represents the first cause of cancer-related deaths. MATERIAL AND METHODS: In a case-control study we compared the frequencies of IL-1B-511 and IL-1B+3954 biallelic polymorphism, and the pentallelic VNTR of IL-IRN in 84 gastric adenocarcinoma paraffin-embedded biopsies and 84 endoscopic biopsies from cancer-free controls. RESULTS: No significant increase in genotypic frequencies in gastric cancer was observed for any of the IL-1B-511 allelic combinations. However, in a logistic regression analysis, a significant association emerged for the IL-1B+3954C carrier genotype (odds ratio (OR): 6.2; 95% confidence intervals (CI) 1.3-28.8). On the other hand, a significantly higher risk was evidenced for the IL-IRN*2/*2 genotype (OR: 7.0; 95% CI2.3-21.5). Only patients with a well/moderately-differentiated adenocarcinoma that were homozygotes for the E-IRN*2/*2 genotype, had a higher risk than the complete gastric cancer group (OR: 8.1, 95% CI 2.5-26.8). Some genotype combinations among IL-1B-511, IL-1B+3954 and IL-IRN showed an increased risk for developing gastric cancer and well/moderate differentiated adenocarcinoma, that was dependent of the presence of IL-IRN*2/*2 genotype. CONCLUSIONS: IL-IRN*2/*2 genotype is associated with increased risk of gastric cancer in the Venezuelan population.
Assuntos
Adenocarcinoma/genética , Predisposição Genética para Doença , Interleucina-1/genética , Polimorfismo Genético , Neoplasias Gástricas/genética , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Neoplasias Gástricas/patologia , Venezuela , Adulto JovemRESUMO
Background: Genetic predisposition may play a role in the prevalence of gastric cancer (GC). Aim: To investigate the relationship between selected interleukin-1 (IL-1) loci polymorphisms and gastric cancer risk in the Central-Western region of Venezuela, where gastric cancer represents the first cause of cancer-related deaths. Material and methods: In a case-control study, we compared the frequencies of IL-1B-511 and IL-1B+3954 biallelic polymorphism, and the pentallelic VNTR of IL-IRN in 84 gastric adenocarcinoma paraffin-embedded biopsies and 84 endoscopic biopsies from cancer-free controls. Results: No significant increase in genotypic frequencies in gastric cancer was observed for any of the IL-1B-511 allelic combinations. However, in alogistic regression analysis, a significant association emerged for the IL- 1B+3954C carrier genotype (odds ratio (OR): 6.2; 95% confidence intervals (CI) 1.3-28.8). On the other hand, a significantly higher risk was evidenced for the IL-IRN*2/*2 genotype (OR: 7.0; 95% CI 2.3-21.5). Only patients with awell/moderately-differentiated adenocarcinoma that were homozygotes for the IL-IRN*2/*2 genotype, had a higher risk than the complete gastric cancer group (OR: 8.1, 95% CI 2.5-26.8). Some genotype combinations among IL-1B-511, IL-1B+3954 and IL-IRN showed an increased risk for developing gastric cancer and well/moderate differentiated adenocarcinoma, that was dependent of the presence of IL-IRN*2/*2 genotype. Conclusions: IL-IRN*2/*2 genotype is associated with increased risk of gastriccancer in the Venezuelan population.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Adenocarcinoma/genética , Predisposição Genética para Doença , Interleucina-1/genética , Polimorfismo Genético , Neoplasias Gástricas/genética , Adenocarcinoma/patologia , Estudos de Casos e Controles , Frequência do Gene , Razão de Chances , Fatores de Risco , Neoplasias Gástricas/patologia , Venezuela , Adulto JovemRESUMO
El polimorfismo del codón 72 del gen TP53 ha sido asociado con un riesgo elevado para el desarrollo de cáncer. Este polimorfismo origina dos variantes de la proteína, una con un residuo de Arginina (CGC), y otra con Prolina (CCC). El objetivo del estudio fue analizar la asociación de este polimorfismo con el riesgo de desarrollar cáncer gástrico en individuos procedentes de la región centroccidental de Venezuela, considerada de alto riesgo para esta neoplasia maligna. El ADN fue extraído de biopsias de adenocarcinoma gástrico incluídas en parafina (n = 65) y biopsias endoscópicas de pacientes con gastritis crónica (n = 87). El polimorfismo del codón 72 de TP53 fue determinado por PCR-RFLP. Se observó un incremento significativo de la frecuencia del alelo Arg en los pacientes con cáncer gástrico (P = 0,037), originando un riesgo 4,6 veces mayor (95% IC 1,0-21,3) de desarrollar esta enfermedad. Se evidenció un incremento del genotipo Arg/Arg en adenocarcinoma gástrico poco diferenciado (OR: 3,1; 95% IC 1,0-9,2), y del genotipo Arg/Pro en adenocarcinoma de moderado/buen grado de diferenciación (OR: 3,5; 95% IC 1,1-11,0) al comparar con el grupo de cáncer gástrico, y este último también al contrastar con los individuos con gastritis crónica (OR: 2,4; 95% IC 1,1-5,2). Los resultados de este estudio sugieren que la condición de portador del alelo Arg podría estar asociado con el desarrollo de cáncer gástrico en esta región de Venezuela.
Codon 72 polymorphism of the tumor suppressor gene TP53 has been associated with a higher risk in the development of several types of cancer. The polymorphism results in a variant protein with either an arginine (CGC) or a proline residue (CCC). The aim of this study was to analyze the association of the TP53 codon 72 polymorphism with the risk of developing gastric cancer in a high-risk population from the central-western region of Venezuela. DNA was extracted from paraffin-embedded gastric adenocarcinoma biopsies (n = 65) and endoscopic biopsies from chronic gastritis patients (n = 87). TP53 codon 72 polymorphism was determined by PCR-RFLP from all samples. Patients with gastric cancer had a significantly higher frequency (P = 0.037) of the Arg allele than those with chronic gastritis. A logistic regression analysis suggested that Arg carrier individuals had a 4.6-fold higher risk (95% CI 1.0-21.3) of developing gastric cancer. An increment of the Arg/Arg genotype was observed in poor-differentiated gastric adenocarcinoma (OR: 3.1; 95% CI 1.0-9.2), and of the Arg/Pro genotype in well/ moderate-differentiated adenocarcinoma samples (OR: 3.5; 95% CI 1.1-11.0), when comparing within the gastric cancer samples; and the last group also when contrasting it with chronic gastritis patients (OR: 2.4; 95% CI 1.1-5.2). The results of this study suggest that the carriage of the Arg allele could be associated with the development of gastric cancer in this Venezuelan population.