El polimorfismo rs12979860 C> T en el gen Interferón lambda 4 no está asociado a riesgo de fibrosis hepática en pacientes chilenos con hepatitis crónica por virus C / Interferon Lambda 4 RS12979860 C> T polymorphism is not associated with liver fibrosis in patients with hepatitis C

Background. Host genetic predispositions may be important determinants of liver fibrosis in patients with chronic hepatitis C (CHC). The association between Interferon-L 4 (IFNL4) rs12979860 C>T polymorphism and risk of liver fibrosis in CHC is contradictory. Aim: To evaluate the impact of IFNL4 rs12979860 polymorphism on the risk of fibrosis in patients with CHC. Material and Methods: One hundred fifty patients with CHC aged 50 ± 11 years (89 females) were genotyped for IFNL4 rs12979860 using real time PCR. Fibrosis present in liver biopsies was assessed using the METAVIR score, comparing patients with either no fibrosis, mild fibrosis, or intermediate fibrosis (F0+F1+F2, n = 96), with patients with severe fibrosis or cirrhosis (F3+F4, n = 54). Results: In F0-F2 patients the distribution of rs12979860 genotypes was 22 CC, 57 CT and 17 TT, whereas in patients F3-F4 the distribution was 10, 29 and 15, respectively. No association between IFNL4 rs12979860 genotype and risk of fibrosis was observed in uni or multivariate analyses. Conclusions: IFNL4 rs12979860 C>T polymorphism is not associated with risk of liver fibrosis in this group of patients with CHC.

Aplicación de grafos acíclicos dirigidos en la evaluación de un set mínimo de ajuste de confusores: un complemento al modelamiento estadístico en estudios epidemiológicos observacionales / Directed acyclic graphs in statistical modelling of epidemiological studies

Background: Confusion in observational epidemiological studies distorts the relationship between exposure and event. "Step by step" regression models, diverts the decision to a statistical algorithm with little causal basis. Directed Acyclic Graphs (DAGs), qualitatively and visually assess the confusion. They can complement the decision on confounder control during statistical modeling. Aim: To evaluate the minimum set of confounders to be controlled in a cause-effect relationship with the use of "step-by-step regression" and DAGs, in a study of arsenic exposure. Material and Methods: We worked with data from Cáceres et al., 2010 in 66 individuals from northern Chile. The interindividual variability in the urinary excretion of dimethyl arsenic acid attributable to the GSTT1 polymorphism was estimated. A causal DAG was constructed using DAGitty v2.3 with the list of variables. A multiple linear regression model with the step-by-step backwards methodology was carried out. Results: The causal diagram included 12 non-causal open pathways. The minimum adjustment set corresponded to the variables "sex", "body mass index" and "fish and seafood ingest". Confusion retention of the multivariate model included normal and overweight status, gender and the interaction between "water intake" and GSTT1. Conclusions: The use of DAG prior to the modeling would allow a more comprehensive, coherent and biologically plausible analysis of causal relationships in public health.

Variantes genéticas de CYP2A6 y su relación con la dependencia tabáquica y el hábito de fumar en una muestra individuos chilenos: Un estudio piloto / Relation of genetic variants of CYP2A6 with tobacco dependence and smoking habit in Chilean subjects: A pilot study

Background: Genetic and metabolic factors associated with nicotine metabolism may be related to smoking behavior. Aim: To assess the prevalence of allelic and genotype variants of CYP2A6 in a sample of Chilean subjects and to evaluate their relationship with smoking and tobacco dependence. Material and Methods: The genotype frequencies for *2, *3 and *4 of CYP2A6*1 (wild type) gene were determined by polymerase chain reaction (PCR) in 54 volunteers. Addiction to tobacco was evaluated using the Fagerstrom Test. The association between the presence of allelic variants of CYP2A6 and smoking and tobacco dependence was evaluated with chi square test. Results: The prevalence of *1, *2 (wt/*2), *3 (wt/*3 or *31*3) and *4 (del/del) were 92.6%, 3.7%, 0% y 3.7%, respectively. No significant association was observed between being a carrier of a variant genotype of CYP2A6 and smoking or tobacco dependence. Conclusions: In this sample of Chilean individuals we did not find a relation between any CYP2A6 genotype with smoking or tobacco dependence.

Caracterización epidemiológica y evolución del cáncer de mama en Arica y Parinacota, Chile 1997-2007 / Epidemiological characterization and evolution of breast cancer patients in the Arica and Parinacota region in Chile, 1997-2007

Objetivo Caracterizar epidemiológicamente el cáncer de mama y su evolución en la Región de Arica y Parinacota para el decenio 1997- 2007, Chile Método Se realizó un estudio descriptivo de tendencia. Se revisaron las historias clínicas de 306 casos pesquisados, consultantes del Policlínico de Oncología Mamaria del Hospital en Red Dr. Juan Noé Crevani. Se realizó un análisis descriptivo univariado de cada variable estudiada y se evaluó la tendencia de la incidencia y mortalidad de cáncer de mama. Resultados De los 306 casos estudiados durante el periodo, el 51,3 por ciento tuvo entre 46 y 65 años de edad, siendo el 13,9 por ciento de origen Aymara. El 70,2 por ciento de las pacientes eran menopáusicas, 98,4 por ciento sin tratamiento hormonal. El 12 por ciento refirió tener antecedentes familiares, de los cuales la hermana fue lo más frecuente. El 84,1 por ciento tuvo el diagnostico de carcinoma ductal infiltrante, un 32,8 por ciento de estos en etapa IIA. De todos los casos, el 31,6 por ciento presentó metástasis múltiple, con 74,7 por ciento en un rango de edad entre of 56 a 94 años. El análisis de la serie indica una tendencia creciente de nuevos casos y una moderada tendencia a la diminución de la tasa de mortalidad. Conclusiones La Región de Arica y Parinacota de Chile, muestra una tendencia creciente absoluta y relativa de nuevos casos de cáncer de mama durante el decenio estudiado. Por otra parte, la tasa mortalidad tendió a la disminución en el periodo. Ambos situaciones se explicarían en parte por el diagnóstico precoz y las políticas de salud implementados.

Objective Epidemiologically characterizing breast cancer in the Arica and Parinacota region in Chile and its evolution during 1997-2007. Method A descriptive, cross-sectional study was performed. All clinical histories for 306 cases of breast cancer were reviewed. All patients were detected through the Arica Juan Noé Crevani Hospital's Oncological Mammary Polyclinic from 1997 to 2007. A descriptive data analysis was made, followed by a tendency analysis. Results 51.3 percent of the 306 cases studied were aged 46 to 65 years, 13.9 percent being of Aymara ethnic origin. 70.2 percent of the women involved in the study were climacteric, 98.4 percent being without hormonal treatment. 12 percent referred to having a family background of cancer, the sister being the most frequently referred to relative. 84.1 percent had a histological diagnosis of infiltrating ductal carcinoma, stage IIA being the most frequently occurring one (32.8 percent). 31.6 percent presented multiple metastases, 74.7 percent of this group being aged 56 to 94. Time series analysis indicated an increasing incidence rate and decreasing mortality rate. Conclusions The Arica and Parinacota region of Chile presented an increasing tendency for new cases of breast cancer during the period being studied which was concentrated during the early stages of evolution. These findings could be explained by the early detection of breast cancer and the implementation of public health policy.

Study of Cytochrome P450 2E1 and its allele Variants in Liver Injury of Nondiabetic, Nonalcoholic Steatohepatitis Obese Women

CYP2E1 enzyme is related to nonalcoholic steatohepatitis (NASH) due to its ability for reactive oxygen species production, which can be influenced by polymorphisms in the gene. The aim of this study was to investigate hepatic levels, activity, and polymorphisms of the CYP2E1 gene to correlate it with clinical and histological features in 48 female obese NASH patients. Subjects were divided into three groups: (i) normal; (ii) steatosis; and (iii) steatohepatitis. CYP2E1 protein level was assayed in microsomes from liver biopsies, and in vivo chlorzoxazone hydroxylation was determined by HPLC. Genomic DNA was isolated for genotype analysis through PCR. The results showed that liver CYP2E1 content was significantly higher in the steatohepatitis (45 percent; p=0.024) and steatosis (22 percent; p=0.032) group compared with normal group. Chlorzoxazone hydroxylase activity showed significant enhancement in the steatohepatitis group (15 percent, p=0.027) compared with the normal group. c2 rare allele of RsallPstl polymorphisms but no C allele of Dral polymorphism was positively associated with CHZ hydroxylation, which in turn is correlated with liver CYP2E1 content (r=0.59; p=0.026). In conclusion, c2 allele is positively associated with liver injury in NASH. This allele may determine a higher transcriptional activity of the gene, with consequent enhancement in pro-oxidant activity of CYP2E1 thus affording liver toxicity.