RESUMO
Background: Recent studies have shown that genetic alterations are associated with the effect of patient geographic location on gallbladder cancer development. Peru has a high incidence of gallbladder cancer, but causative factors have not yet been identified. We examined the frequency of mutations in TP53 and K-ras genes in Peruvian patients with gallbladder cancer, and compared this with data from Bolivia, Hungary, Chile, and Japan, which have a high gallbladder cancer incidence. Methods: DNA was extracted from formalin-fixed paraffin-embedded gallbladder tissue sections of 30 gallbladder cancer patients (9 men and 21 women) obtained using microdissection. Mutations in exons 5 to 8 of TP53 and codons 12, 13, and 61 of K-ras were examined using direct sequencing. Results: TP53 mutations were observed in 10 (33.3%) of patients, but K-ras mutations were absent. Nine (90%) TP53 mutations were point mutations (7 missense and 2 silent mutations), and the most frequent substitution was a G:C to A:T transition. G:C to A:T transitions at the CpG site or G:C to T:A transversions were found in one patient each. No significant differences were found in the frequency of TP53 and K-ras mutations among patients in the 5 countries. Conclusions: Our findings suggest that endogenous mechanisms and exogenous carcinogens may affect the carcinogenic process in Peruvian gallbladder cancer patients, similar to that in Bolivian patients. Further studies with a larger sample size are needed to clarify these findings.
Assuntos
Neoplasias da Vesícula Biliar/genética , Mutação/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Bolívia , Éxons/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peru , Proto-Oncogene MasRESUMO
Bolivia is one of the countries with a high intestinal helminth and protozoan infection rate. Despite the high prevalence of the parasitic infection, nationwide preventive measures for Bolivian children have not yet been implemented. We evaluated the effect of mass stool examination and treatment as a strategy for decreasing the infection rate. This study was conducted between 2013 and 2015 in children aged 2-18 years. A total of 2,033 stool samples (575 in 2013, 815 in 2014 and 642 in 2015) were collected and examined using the formalin-ether medical sedimentation method. As an anthelminthic medicine, nitazoxanide was given to all infected children within 2 months post-examination, each year. The effect of mass stool examination and treatment was evaluated based on the changes in the overall or individual parasitic infection rates during the study period. The overall parasitic infection rate decreased significantly from 65.2% in 2013 to 43.0% in 2015; a 22.2 percentage point decrease (P<0.001). Protozoan infection accounted for a large portion of the parasitic infections, in the following rates: 62.4% in 2013, 49.3% in 2014, and 41.0% in 2015. The rate of the most common helminth infection, Hymenolepis nana, decreased significantly from 9.0% in 2013 to 6.4% in 2014 to 3.4% in 2015 (P<0.001). Prevalence of the most common pathogenic protozoan infection, Entamoeba histolytica, decreased significantly from 19.0% in 2013 to 3.0% in 2015 (P<0.001). Conversely, the rate of Giardia intestinalis increased significantly from 16.5% in 2013 to 21.2% in 2015 (P<0.01). Mass stool examination and treatment for intestinal helminth and protozoan infections was effective for decreasing the overall parasitic infection rate in the study population, excluding Giardia intestinalis. Further studies on the long-term effect of mass stool examination and treatment for decreasing all intestinal parasitic infection rates in Bolivian children are needed.
Assuntos
Entamebíase/tratamento farmacológico , Fezes/parasitologia , Giardíase/tratamento farmacológico , Helmintíase/tratamento farmacológico , Himenolepíase/tratamento farmacológico , Enteropatias Parasitárias/tratamento farmacológico , Enteropatias Parasitárias/epidemiologia , Programas de Rastreamento , Infecções por Protozoários/epidemiologia , Adolescente , Animais , Bolívia/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Entamoeba histolytica/isolamento & purificação , Entamebíase/epidemiologia , Entamebíase/parasitologia , Entamebíase/prevenção & controle , Feminino , Giardia lamblia/isolamento & purificação , Giardíase/epidemiologia , Giardíase/parasitologia , Giardíase/prevenção & controle , Helmintíase/epidemiologia , Helmintíase/parasitologia , Helmintíase/prevenção & controle , Humanos , Himenolepíase/epidemiologia , Himenolepíase/parasitologia , Himenolepíase/prevenção & controle , Hymenolepis/isolamento & purificação , Enteropatias Parasitárias/prevenção & controle , Masculino , Nitrocompostos , Prevalência , Estudantes , Tiazóis/uso terapêutico , Adulto JovemRESUMO
The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano-Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.
Assuntos
Biomarcadores Tumorais/genética , Citocromo P-450 CYP1A1/genética , Neoplasias da Vesícula Biliar/etiologia , Glutationa Transferase/genética , Polimorfismo Genético/genética , Proteína Supressora de Tumor p53/genética , Adulto , Bolívia , Estudos de Casos e Controles , Feminino , Seguimentos , Vesícula Biliar/metabolismo , Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/patologia , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prognóstico , Fatores de RiscoRESUMO
Our previous study detected aflatoxins in red chili peppers from Chile, Bolivia, and Peru, each of which have a high incidence of gallbladder cancer (GBC). Since the aflatoxin B1 concentration was not so high in these peppers, it is important to clarify the presence of other mycotoxins. Here we attempted to determine any associations between the concentrations of aflatoxins and ochratoxin A (OTA) in red chili peppers, and the corresponding GBC incidences. We collected red chili peppers from three areas in Peru: Trujillo (a high GBC incidence area), Cusco (an intermediate GBC incidence area), and Lima (a low GBC incidence rate), and from Chile and Bolivia. Aflatoxins and OTA were extracted with organic solvents. The concentrations of aflatoxins B1, B2, G1, and G2, and OTA were measured by high-performance liquid chromatography. The values obtained were compared with the incidence of GBC in each area or country. All of the red chili peppers from the three areas showed contamination with aflatoxins below the Commission of the European Communities (EC) recommended limits (5 µg/kg), but the OTA contamination of two samples was above the EC recommended limit (15 µg/kg). The mean concentrations of OTA in the peppers from Chile (mean 355 µg/kg, range <5-1,059 µg/kg) and Bolivia (mean 207 µg/kg, range 0.8-628 µg/kg), which has a high incidence of GBC, were higher than that in Peru (14 µg/kg, range <5-47 µg/kg), which has an intermediate GBC incidence. The OTA contamination in the red chili peppers from Chile, Bolivia, and Peru was stronger than that of aflatoxins. Our data suggest that OTA in red chili peppers may be associated with the development of GBC.
Assuntos
Capsicum/química , Carcinógenos/farmacologia , Contaminação de Alimentos/análise , Neoplasias da Vesícula Biliar/induzido quimicamente , Neoplasias da Vesícula Biliar/epidemiologia , Ocratoxinas/efeitos adversos , Bolívia/epidemiologia , Carcinógenos/análise , Chile/epidemiologia , Cromatografia Líquida de Alta Pressão , Humanos , Incidência , Ocratoxinas/análise , Peru/epidemiologia , Fatores de RiscoRESUMO
Chilean red chili peppers contaminated with aflatoxins were reported in a previous study. If the development of gallbladder cancer (GBC) in Chile is associated with a high level of consumption of aflatoxin-contaminated red chili peppers, such peppers from other countries having a high GBC incidence rate may also be contaminated with aflatoxins. We aimed to determine whether this might be the case for red chili peppers from Bolivia and Peru. A total of 7 samples (3 from Bolivia, 4 from Peru) and 3 controls (2 from China, 1 from Japan) were evaluated. Aflatoxins were extracted with acetonitrile:water (9:1, v/v) and eluted through an immuno-affinity column. The concentrations of aflatoxins B1, B2, G1, and G2 were measured using high-performance liquid chromatography (HPLC), and then the detected aflatoxins were identified using HPLC-mass spectrometry. In some but not all of the samples from Bolivia and Peru, aflatoxin B1 or aflatoxins B1 and B2 were detected. In particular, aflatoxin B1 or total aflatoxin concentrations in a Bolivian samples were above the maximum levels for aflatoxins in spices proposed by the European Commission. Red chili peppers from Bolivia and Peru consumed by populations having high GBC incidence rates would appear to be contaminated with aflatoxins. These data suggest the possibility that a high level of consumption of aflatoxin-contaminated red chili peppers is related to the development of GBC, and the association between the two should be confirmed by a case-control study.