Preliminary Pharmacogenomic-Based Predictive Models of Tamoxifen Response in Hormone-dependent Chilean Breast Cancer Patients.

Tamoxifen (TAM), a selective oestrogen receptor modulator, is one of the most used treatments in oestrogen receptor-positive (ER+) early and metastatic breast cancer (BC) patients. The response to TAM has a high degree of inter-individual variability. This is mainly due to genetic variants in CYP2D6 gene, as well as other genes encoding proteins involved in the TAM pharmacokinetic and/or pharmacodynamic. Therefore, prediction of the TAM response using these genetic factors together with other non-genetic variables may be relevant to improve breast cancer treatment. Thus, in this work, we used genetic polymorphisms and clinical variables for TAM response modelling. One hundred sixty-two ER + BC patients with 2 years of TAM treatment were retrospectively recruited, and the genetic polymorphisms CYP2D6*4, CYP3A4*1B (CYP3A4*1.001), CYP3A5*3, UGT2B7*2, UGT2B15*2, SULT1A1*2, and ESRA V364E were analyzed by PCR-RFLP. Concomitantly, the therapeutic response was obtained from clinical records for association with genotypes using univariate and multivariate biostatistical models. Our results show that UGT2B15*1/*2 genotype protects against relapse (OR = 0.09; p = 0.02), CYP3A5*3/*3 genotype avoids endometrial hyperplasia (OR = 0.07; p = 0.01), SULT1A1*1/*2 genotype avoids vaginal bleeding (OR = 0.09; p = 0.03) and ESRA 364E/364E genotype increases the probability of vaginal bleeding (OR = 5.68; p = 0.02). Logistic regression models, including genomic and non-genomic variables, allowed us to obtain preliminary predictive models to explain relapse (p = 0.010), endometrial hyperplasia (p = 0.002) and vaginal bleeding (p = 0.014). Our results suggest that the response to TAM treatment in ER + BC patients might be associated with the presence of the studied genetic variants in UGT2B15, CYP3A5, SULT1A1 and ESRA genes. After clinical validation protocols, these models might be used to help to predict a percentage of BC relapse and adverse reactions, improving the individual response to TAM-based treatment.

An exploratory double-blind, randomized, placebo-controlled study to assess the efficacy of CitruSlim on body composition and lipid parameters in obese individuals.

The prevalence of obesity in developing and developed countries has been well recognized, and the worldwide obesity rates have nearly tripled since 1975, according to the World Health Organization. CitruSlim, a standardized product containing a blend of Citrus bergamia and Eurycoma longifolia, can reduce cortisol, cholesterol, triglycerides, and hyperglycemia. These properties can contribute to reduction in body weight or body mass index (BMI) in obese patients. A randomized, double-blind, placebo-controlled clinical study was designed to evaluate the efficacy and tolerability of CitruSlim in body weight management in obese individuals, and the results were compared with that of placebo. A total of 97 participants were allocated, randomized, and treated with CitruSlim high-dose (HD, 400 mg), CitruSlim low-dose (LD, 200 mg), and placebo for 112 days. At the end of the study, CitruSlim HD and CitruSlim LD significantly reduced BMI compared to the placebo group and were well tolerated; however, it did not improve parameters associated with dyslipidemia and metabolic disturbances. The study findings suggested that CitruSlim was effective in reducing body weight in obese patients.

Contribution of Anthropogenic Factors and Climate Variables to Human Cystic Echinococcosis Mortality in Chile (2001-2011).

Here we assess the effect of weather and anthropogenic environmental variables, particularly urbanization, on cystic echinococcosis mortality in Chile from 2001 to 2011 using a nonparametric regression model, multivariate adaptive regression splines, and Poisson nonlinear regression models. This study integrated data from various sources on weather and anthropogenic variables. The canine population had the greatest influence on human cystic echinococcosis mortality during the period analyzed. Urbanization among anthropogenic variables and temperature and precipitation among the weather-related variables were the main factors related to cystic echinococcosis deaths. Deaths decreased with urbanization level. Temperature showed a nonlinear impact on mortality, with an optimum value ∼11°C. Public policies aimed at improving safe management of companion animal populations are crucial in controlling the spread of this disease. Effective animal management strategies would have wide-ranging public health benefits, advance the welfare of companion animals and livestock, and decrease the number of human cystic echinococcosis cases.

The role of phase I and II genetic polymorphisms, smoking, alcohol and cancer family history, in the risk of developing testicular cancer.

BACKGROUND: Testicular cancer (TCa) is a malignant tumor with highest incidence and mortality rates in Chile. The genes coding for cytochrome P450, glutathione-S-transferases (GSTs), and UDP glucuronyl transferases (UGT) participate in the biotransformation and detoxification of xenobiotics. Mutations in these genes have been associated with a high incidence of various types of cancer and an increased risk of presenting adverse reactions to drugs. OBJECTIVE: The aim of this study was to relate the presence of genetic polymorphisms in cytochrome P450 1A1 (CYP1A1), CYP3A4, GSTM1, GSTP1, GSTT1, and UGT1A1 genes and nongenetic factors with the risk of developing TCa. METHODS: A total of 276 volunteers from the Chilean general population and 251 Chilean TCa patients were recruited for the study. Genotypic analyses were performed using qPCR and PCR-RFLP. RESULTS: Variant alleles found to increase the risk of developing TCa were CYP1A1*2C (rs1048943), GSTP1 (rs1695), and GSTT1null, especially when in conjunction with a cancer family history and/or a smoking habit. The results of the multivariate analysis showed that the presence of variant alleles of GSTP1 (rs1695) together with a smoking habit and a family history of cancer accounted for a 15.9% risk of developing TCa in the Chilean population. CYP1A1*2C, GSTM1null, GSTT1null, and GSTP1 (rs1695) are statistically related to the risk of appearance of TCa, alone or associated with nongenetic factors. CONCLUSION: Therefore, phase I and II variant alleles might be useful in evaluating susceptibility to TCa in the studied population.

A double-blind, randomized, placebo-controlled study to assess the efficacy of Andrographis paniculata standardized extract (ParActin®) on pain reduction in subjects with knee osteoarthritis.

Andrographis paniculata Wall (Acanthaceae) is becoming more recognized for its anti-inflammatory and antioxidant properties. A randomized, double-blind, placebo-controlled study was conducted to assess the efficacy of an andrographolide-containing supplement, ParActin® (300 and 600 mg daily), on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain reduction in patients with knee osteoarthritis. Joint stiffness, physical function, changes in the SF-36 quality of life questionnaire, a fatigue scale, and safety were also evaluated. A total of 103 male and female patients with I-II osteoarthritis of the knee joint were assessed. Patients treated with 300 or 600 mg/day of ParActin® showed a significant reduction in pain at days 28, 56, and 84 compared with a placebo group. WOMAC stiffness scores, physical function score, and the fatigue score showed a significant improvement in both ParActin®-treated groups compared with the placebo group. At the end of the study, the quality of life (SF-36 questionnaire) and Functional Assessment of Chronic Illness Therapy (FACIT) scores showed significant improvements in both ParActin®-treated groups compared with the placebo group. Overall, it can be concluded that ParActin® in 300 and 600 mg/day dosages were found to be effective and safe in reducing pain in individuals suffering from mild to moderate knee osteoarthritis.

Association Study Among Candidate Genetic Polymorphisms and Chemotherapy-Related Severe Toxicity in Testicular Cancer Patients.

Testicular cancer is one of the most commonly occurring malignant tumors in young men with fourfold higher rate of incidence and threefold higher mortality rates in Chile than the average global rates. Surgery is the initial line of treatment for testicular cancers, and is generally followed by chemotherapy, usually with combinations of bleomycin, etoposide, and cisplatin (BEP). However, the adverse effects of chemotherapy vary significantly among individuals; therefore, the present study explored the association of functionally significant allelic variations in genes related to the pharmacokinetics/pharmacodynamics of BEP and DNA repair enzymes with chemotherapy-induced toxicity in BEP-treated testicular cancer patients. We prospectively recruited 119 patients diagnosed with testicular cancer from 2010 to 2017. Genetic polymorphisms were analyzed using PCR and/or qPCR with TaqMan ®probes. Toxicity was evaluated based on the Common Terminology Criteria for Adverse Events, v4.03. After univariate analyses to define more relevant genetic variants (p < 0.2) and clinical conditions in relation to severe (III-IV) adverse drug reactions (ADRs), stepwise forward multivariate logistic regression analyses were performed. As expected, the main severe ADRs associated with the non-genetic variables were hematological (neutropenia and leukopenia). Univariate statistical analyses revealed that patients with ERCC2 rs13181 T/G and/or CYP3A4 rs2740574 A/G genotypes are more likely to develop alopecia; patients with ERCC2 rs238406 C/C genotype may develop leukopenia, and patients with GSTT1-null genotype could develop lymphocytopenia (III-IV). Patients with ERCC2 rs1799793 A/A were at risk of developing severe anemia. The BLMH rs1050565 G/G genotype was found to be associated with pain, and the GSTP1 G/G genotype was linked infection (p < 0.05). Multivariate analysis showed an association between specific ERCC1/2 genotypes and cumulative dose of BEP drugs with the appearance of severe leukopenia and/or febrile neutropenia. Grades III-IV vomiting, nausea, and alopecia could be partly explained by the presence of specific ERCC1/2, MDR1, GSTP1, and BLMH genotypes (p < 0.05). Hence, we provide evidence for the usefulness of pharmacogenetics as a tool for predicting severe ADRs in testicular cancer patients treated with BEP chemotherapy.

[Interferon Lambda 4 RS12979860 C>T polymorphism is not associated with liver fibrosis in patients with hepatitis C]. / 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.

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.

[Directed acyclic graphs in statistical modelling of epidemiological studies]. / 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.

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.

Arsenic exposure, profiles of urinary arsenic species, and polymorphism effects of glutathione-s-transferase and metallothioneins.

This study assessed the effects of polymorphic variants of gutathione-S-transferase and metallothioneins on profiles of urinary arsenic species. Drinking groundwater from Margarita and San Fernando, Colombia were analyzed and the lifetime average daily dose (LADD) of arsenic was determined. Specific surveys were applied to collect demographic information and other exposure factors. In addition, GSTT1-null, GSTM1-null, GSTP1-rs1695 and MT-2A-rs28366003 genetic polymorphisms were evaluated, either by direct PCR or PCR-RFLP. Urinary speciated arsenic concentrations were determined by HPLC-HG-AFS for species such as AsIII, AsV, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and total urinary As (TuAs). Primary methylation index (PMI) and secondary methylation index (SMI) were also calculated as indicators of the metabolic capacity. Polymorphisms effects were tested using multivariate analysis, adjusted by potential confounders. The As concentrations in groundwater were on average 34.6 ± 24.7 µg/L greater than the WHO guideline for As (10 µg/L). There was a correlation between As concentrations in groundwater and TuAs (r = 0.59; p = 0.000). Urinary inorganic arsenic (%InAs) was associated with GSTP1, LADD, GSTP1*Age, GSTP1*alcohol consumption (r2 = 0.43; likelihood-ratio test, p = 0.000). PMI was associated with sex (r2 = 0.20; likelihood-ratio test, p = 0.007). GSTP1 (AG + GG) homozygotes/heterozygotes could increase urinary %InAs and decrease the PMI ratio in people exposed to low and high As from drinking groundwater. Therefore, the explanatory models showed the participation of some covariates that could influence the effects of the polymorphisms on these exposure biomarkers to As.

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.

Cognitive performance among cohorts of children exposed to a waste disposal site containing heavy metals in Chile.

Between 1984 and 1998, people living in Arica were involuntarily exposed to metal-containing waste stored in the urban area. The study aims to determine whether children who lived near the waste disposal site during early childhood experienced negative effects on their cognitive development. The cognitive performance was assessed using the Wechsler Intelligence Scale for Children. The exposure variable was defined by the year of birth in three categories: (1) Pre-remediation (born before 1999); (2) During-remediation (born between 1999 and 2003); and (3) Post-remediation (born after 2003). In the crude analysis, a difference of 10 points in the IQ average was observed between the group born in the pre- (81.9 points) and post-remediation period (91.1 points). The difference between both groups was five times higher as compared to children of similar age and socioeconomic status in other cities of Chile. This result could be related with a period of high potential for exposure to this contaminated site.

Caries experience and use of dental services in rural and urban adults and older adults from central Chile.

OBJECTIVE: To determine whether there is a relationship between the use of dental services and caries experience in adults and older adults from central Chile. MATERIALS AND METHODS: A sample of 453 adults, 35-44 years of age, and 438 older adults, 65-74 years of age, was interviewed and examined using World Health Organisation (WHO) methods. Sociodemographic variables were also registered. Caries experience was assessed using the Decayed, Missing and Filled teeth (DMFT) index. Multiple linear regression models were used to determine whether there was an association between the independent variables and caries experience. RESULTS: Caries prevalence was 99.6% for adults [DMFT score = 14.89 (±6.16)] and 99.8% for older adults [DMFT score = 25.68 (±6.49)]. Less than half of the population - 41.7% of adults and 31.5% of older adults - received dental care. Regardless of the age group, there were no differences in the DMFT score between those who received and those who did not receive attention (P > 0.05). When the DMFT findings were analysed in greater detail, people who received dental care and urban participants had more fillings (P < 0.05) than did those who were not provided with attention or lived in rural areas, who, in turn, had more missing teeth (P < 0.05). A higher educational level was associated with a decrease of 1.15 DMFT points (P = 0.003) in the group of older adults. CONCLUSIONS: Adults and older adults from the Maule Region showed severe dental damage from caries. Although rurality and use of services do not seem to affect caries experience, they are associated with differences in fillings and missing teeth.

Personal exposure to particulate matter in commuters using different transport modes (bus, bicycle, car and subway) in an assigned route in downtown Santiago, Chile.

The objective of this study was to compare personal exposure to particulate matter (fine and ultrafine particles) in commuters using different transport modes (bicycle, bus, car and subway) in a busy, assigned route in downtown Santiago, Chile. Volunteers carrying personal samplers completed scheduled commutes during the morning rush hours, while central site measurements were conducted in parallel. A total of 137 valid commutes were assessed. The impact of central site, traffic and other variables was explored with regression models. PM2.5 personal concentrations were equal to or slightly above central site measurements, while UFP personal concentrations were above them. Regression models showed impacts of both background levels and traffic emissions on personal PM2.5 and UFP exposure. Traffic impacts varied with transport modes. Estimates of traffic impacts on personal PM2.5 exposure were 2.0, 13.0, 16.9 and 17.5 µg m(-3), for car, bicycle, subway and bus, respectively; while for UFP exposure were 8400, 16 200, 25 600 and 30 100 counts per cm(3), for subway, car, bicycle and bus, respectively. After controlling the central site and transport mode, higher temperatures increased PM2.5 exposure and decreased UFP ones, while the wind direction affected UFP personal exposure. In conclusion, we found significant impacts of both central site background measurements and traffic emissions on personal exposure of volunteer commuters in an assigned route in Santiago, with impacts varying with transport modes.

Impact of CYP1A1, GSTM1, and GSTT1 polymorphisms in overall and specific prostate cancer survival.

OBJECTIVE: Prognostic biomarkers that distinguish between patients with good or poor outcome can be used to guide decisions of whom to treat and how aggressively. In this sense, several groups have proposed genetic polymorphisms as potential susceptibility and prognostic biomarkers; however, their validity has not been proven. Thus, the main goal of the present work was to investigate the potential role of single and combined CYP1A1, GSTM1, and GSTT1 genotypes as modifiers of cancer survival in Chilean patients with prostate cancer. METHODS AND MATERIALS: A total of 260 histologically confirmed patients were recruited from a voluntary screening, and genomic DNA was obtained from their blood samples for genotyping analyses to detect the CYP1A1*2A polymorphism and GSTM1 and GSTT1 deletions. The progression of illness and mortality were estimated with a median follow-up of 8.82 years. Adjusted estimated genotype risks were evaluated by hazard ratio and 95% CI using the Cox proportional model. In addition, the Kaplan-Meier survival method and log-rank test were used to evaluate patient survival with regard to genotype. RESULTS: The 9-year overall and specific survival rates were 67.6% and 36.6% in the GSTT1null group, 67.6% and 58.7% in the GSTM1non-null group, 69.0% and 51.6% in the *1A/*2A group, 63.9% and 61.5% in the *2A/*2A group vs. 76.2% and 62.3% in the GSTT1non-null group, 82.3% and 50% in the GSTM1null group, and 83.7% and 56.3% in the *1A/*1A group, respectively. The hazard ratios and the Kaplan-Meier curve results demonstrate that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes are significantly associated with mortality. Our study has two main limitations: a relatively small sample size and a low global mortality percentage (25.4%); thus, we need to continue the follow-up to confirm these findings. CONCLUSIONS: Our results suggest that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes may be good prognosis markers, particularly in patients with high-risk tumors.

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

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.

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.

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

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 % of the 306 cases studied were aged 46 to 65 years, 13.9 % being of Aymara ethnic origin. 70.2 % of the women involved in the study were climacteric, 98.4 % being without hormonal treatment. 12 % referred to having a family background of cancer, the sister being the most frequently referred to relative. 84.1 % had a histological diagnosis of infiltrating ductal carcinoma, stage IIA being the most frequently occurring one (32.8 %). 31.6 % presented multiple metastases, 74.7 % 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.

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.

Modelación de episodios críticos de contaminación por material particulado (PM10) en Santiago de Chile. Comparación de la eficiencia predictiva de los modelos paramétricos y no paramétricos / Modeling critical episodes of air pollution by PM10 in Santiago, Chile. Comparison of the predictive efficiency of parametric and non-parametric statistical models

Objetivo Evaluar la eficiencia predictiva de modelos estadísticos paramétricos y no paramétricos para predecir episodios críticos de contaminación por material particulado PM10 del día siguiente, que superen en Santiago de Chile la norma de calidad diaria. Una predicción adecuada de tales episodios permite a la autoridad decretar medidas restrictivas que aminoren la gravedad del episodio, y consecuentemente proteger la salud de la comunidad. Método Se trabajó con las concentraciones de material particulado PM10 registradas en una estación asociada a la red de monitorización de la calidad del aire MACAM-2, considerando 152 observaciones diarias de 14 variables, y con información meteorológica registrada durante los años 2001 a 2004. Se ajustaron modelos estadísticos paramétricos Gamma usando el paquete estadístico STATA v11, y no paramétricos usando una demo del software estadístico MARS v 2.0 distribuida por Salford-Systems. Resultados Ambos métodos de modelación presentan una alta correlación entre los valores observados y los predichos. Los modelos Gamma presentan mejores aciertos que MARS para las concentraciones de PM10 con valores <240μg/m3 para el año 2001, y los modelos MARS presentan mejores aciertos para aquellas que exceden los 240μg/m3 de PM10 para todos los años. Conclusiones Los modelos MARS son más eficientes para predecir episodios graves de alta contaminación por PM10 y posibilitan a la autoridad sanitaria adoptar restricciones preventivas que aminoren su efecto sobre la salud de la población. Esto se explicaría porque MARS corrige las variaciones de la serie a lo largo del tiempo, ajustando mejor la curva asociada a la concentración de PM10 (AU)

Objective To evaluate the predictive efficiency of two statistical models (one parametric and the other non-parametric) to predict critical episodes of air pollution exceeding daily air quality standards in Santiago, Chile by using the next day PM10 maximum 24h value. Accurate prediction of such episodes would allow restrictive measures to be applied by health authorities to reduce their seriousness and protect the community’s health. Methods We used the PM10 concentrations registered by a station of the Air Quality Monitoring Network (152 daily observations of 14 variables) and meteorological information gathered from 2001 to 2004. To construct predictive models, we fitted a parametric Gamma model using STATA v11 software and a non-parametric MARS model by using a demo version of Salford-Systems. Results Both models showed a high correlation between observed and predicted values. However, the Gamma model predicted PM10 values below 240μg/m3 more accurately than did MARS. The latter was more efficient in predicting PM10 values above 240μg/m3 throughout the study period. Conclusion MARS models are more efficient in predicting extreme PM10 values and allow health authorities to adopt preventive methods to reduce the effects of these levels on the population’s health. The reason for this greater accuracy may be that MARS models correct variations in the series over time, thus better fitting the curve associated with PM10 concentrations (AU)