Aflatoxin B1 exposure and liver cirrhosis in Guatemala: a case-control study.

OBJECTIVE: In Guatemala, cirrhosis is among the 10 leading causes of death, and mortality rates have increased lately. The reasons for this heavy burden of disease are not clear as the prevalence of prominent risk factors, such as hepatitis B virus, hepatitis C virus and heavy alcohol consumption, appears to be low. Aflatoxin B1 (AFB1) exposure, however, appears to be high, and thus could be associated with the high burden of cirrhosis. Whether AFB1 increases the risk of cirrhosis in the absence of viral infection, however, is not clear. DESIGN: Cirrhosis cases (n=100) from two major referral hospitals in Guatemala City were compared with controls (n=200) from a cross-sectional study. Logistic regression was used to estimate the ORs and 95% CIs of cirrhosis and quintiles of AFB1 in crude and adjusted models. A sex-stratified analysis was also conducted. RESULTS: The median AFB1 level was significantly higher among the cases (11.4 pg/mg) than controls (5.11 pg/mg). In logistic regression analyses, higher levels of AFB1 was associated with cirrhosis (quintile 5 vs quintile 1, OR: 11.55; 95% CI 4.05 to 32.89). No attenuation was observed with adjustment by sex, ethnicity, hepatitis B virus status, and heavy alcohol consumption. A significantly increasing trend in association was observed in both models (p trend <0.01). Additionally, the cirrhosis-AFB1 association was more prominent among men. CONCLUSIONS: The current study found a significant positive association between AFB1 exposure and cirrhosis. Mitigation of AFB1 exposure and a better understanding of additional risk factors may be important to reduce the burden of cirrhosis in Guatemala.

Pharmacogenetic research activity in Central America and the Caribbean: a systematic review.

AIM: The present review was aimed at analyzing the pharmacogenetic scientific activity in Central America and the Caribbean. MATERIALS & METHODS: A literature search for pharmacogenetic studies in each country of the region was conducted on three databases using a list of the most relevant pharmacogenetic biomarkers including 'phenotyping probe drugs' for major drug metabolizing enzymes. The review included 132 papers involving 47 biomarkers and 35,079 subjects (11,129 healthy volunteers and 23,950 patients). RESULTS: The country with the most intensive pharmacogenetic research was Costa Rica. The most studied medical therapeutic area was oncology, and the most investigated biomarkers were CYP2D6 and HLA-A/B. Conclusion: Research activity on pharmacogenetics in Central American and the Caribbean populations is limited or absent. Therefore, strategies to promote effective collaborations, and foster interregional initiatives and research efforts among countries from the region could help for the rational clinical implementation of pharmacogenetics and personalized medicine.

Valor diagnóstico de las proteínas uPAR en sangre para el cáncer gástrico en Guatemala / Diagnostic value of blood uPAR proteins for gastric cancer in Guatemala

El cáncer gástrico es la neoplasia más frecuente del tubo digestivo, Guatemala posee altas tasas de incidencia y mortalidad. Helicobacter pylori se ha identificado como un carcinógeno gástrico, especialmente si la infección es por cepas que expresen factor de virulencia CagA, asociado a lesiones atróficas y precancerosas. Reportes previos indican que el análisis de biopsias gástricas en pacientes positivos para H. pylori, muestran un incremento de la expresión del activador del plasminógeno uroquinasa (uPA) y su receptor (uPAR). El presente estudio tuvo como objetivo determinar el valor diagnóstico de uPAR en sangre como marcador de cáncer gástrico en Guatemala y la asociación de uPAR con la infección por de H. pylori. Se tomaron muestras sanguíneas de pacientes diagnosticados con cáncer gástrico (n = 68) y controles sanos apareados por edad y sexo (n = 136) en cuatro instituciones de la ciudad de Guatemala, se determinó uPAR e IgG anti H. pylori por metodología Elisa. Los niveles de uPAR en pacientes con cáncer estaban significativamente elevados (p < .001), no se encontró diferencia por edad, sexo, apariencia macroscópica o microscópica del tumor. El cáncer gástrico se asoció significativamente a H. pylori (p = .03). El coeficiente de correlación biserial indica una relación negativa débil (rb = -0.01, p = .443) entre uPAR y H. pylori. Las curvas ROC en uPAR reportaron alta precisión (área bajo la curva = .80) para identificar cáncer gástrico. Estos resultados sugieren que los niveles séricos de uPAR pueden tener valor en el diagnóstico cáncer gástrico.

Gastric cancer is the most frequent neoplasm of the digestive tract, Guatemala has high incidence and mortality rates. Helicobacter pylori has been identified as a gastric carcinogen, especially if the infection is by strains expressing virulence factor CagA which is associated with atrophic and precancerous lesions. Previous reports indicate that gastric biopsy analyses in H. pylori positive patients show increased expression of urokinase plasminogen activator (uPA) and its receptor (uPAR). The present study aimed to determine the diagnostic value of uPAR in blood as a marker of gastric cancer in Guatemala and the association of uPAR with infection by of H. pylori. Blood samples were collected from patients diagnosed with gastric cancer (n = 68) and healthy controls matched by age and sex (n = 136) at four institutions in Guatemala City and analyzed for uPAR and anti-H. pylori IgG. uPAR levels in cancer patients were found to be significantly elevated (p <.001), but were not influenced by age, sex, macroscopic or microscopic appearance of the tumor. Gastric cancer was significantly associated with H. pylori (p = .03). The serial correlation analysis used to determine the correlation of uPAR with H. pylori showed that there is a non-significant weak negative Pearson's correlation coefficient (r = -0.01, p = .443) between both. The ROC curves for uPAR indicated high precision (AUC = 0.80) for detection of gastric cancer. These results suggest that serum uPAR levels may be valuable in the diagnosis of gastric cancer.