Metabolomic Signatures of Exposure to Nitrate and Trihalomethanes in Drinking Water and Colorectal Cancer Risk in a Spanish Multicentric Study (MCC-Spain).

We investigated the metabolomic profile associated with exposure to trihalomethanes (THMs) and nitrate in drinking water and with colorectal cancer risk in 296 cases and 295 controls from the Multi Case-Control Spain project. Untargeted metabolomic analysis was conducted in blood samples using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. A variety of univariate and multivariate association analyses were conducted after data quality control, normalization, and imputation. Linear regression and partial least-squares analyses were conducted for chloroform, brominated THMs, total THMs, and nitrate among controls and for case-control status, together with a N-integration model discriminating colorectal cancer cases from controls through interrogation of correlations between the exposure variables and the metabolomic features. Results revealed a total of 568 metabolomic features associated with at least one water contaminant or colorectal cancer. Annotated metabolites and pathway analysis suggest a number of pathways as potentially involved in the link between exposure to these water contaminants and colorectal cancer, including nicotinamide, cytochrome P-450, and tyrosine metabolism. These findings provide insights into the underlying biological mechanisms and potential biomarkers associated with water contaminant exposure and colorectal cancer risk. Further research in this area is needed to better understand the causal relationship and the public health implications.

Endoscopic findings unrelated to portal hypertension in patients with liver cirrhosis undergoing a varicose vein screening programme. / Hallazgos endoscópicos no relacionados con hipertensión portal en pacientes con cirrosis hepática sometidos a un programa de cribado de varices.

AIM: To determine the prevalence of endoscopic lesions unrelated with portal hypertension in patients with cirrhosis. PATIENTS AND METHODS: Cross-sectional study including a consecutive cohort of patients with liver cirrhosis enrolled in a screening program of oesophageal varices who underwent an upper gastrointestinal endoscopy from November, 2013, to November, 2018. Clinical predictors of endoscopic lesions unrelated to portal hypertension were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 379 patients were included. The most frequent aetiology of liver disease was alcohol consumption (60.4%). The prevalence of endoscopic lesions unrelated with portal hypertension was 39.6% (n=150). Among 96 patients with peptic lesions, urease was obtained in 56.2% of patients (positive in 44.4% of them). The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. The prevalence of endoscopic lesions unrelated to portal hypertension was not associated with age, gender, liver function or ultrasound findings of portal hypertension. Smokers had a trend to increased prevalence of endoscopic lesions unrelated to portal hypertension (43.2% vs. 34.6%; p=0.09), particularly peptic ulcer (6.4% vs. 0.6%; p=0.05) and peptic duodenitis (17.3% vs. 6.3%; p=0.002). Active smoking was the only independent predictor of peptic ulcer or duodenitis (OR=2.56; p=0.017). CONCLUSION: Active smoking is a risk factor for endoscopic lesions unrelated to portal hypertension. This finding should be further investigated to reassess endoscopic screening programs in cirrhotic smokers.

The role of calcium and vitamin D dietary intake on risk of colorectal cancer: systematic review and meta-analysis of case-control studies.

PURPOSE: The aim of this study is to analyze the current evidence about the relationships between calcium/vitamin D and CRC based on case-control studies according to sex, tumor location and continental region to complement the information obtained in meta-analyses of other designs. METHODS: The articles were located in three databases (PUBMED, EMBASE and SCOPUS), they should be written in English language, with a case and control design and published between 1 January 1970 and 31 October 2019. RESULTS: There were 37 selected studies, 32 for intake of calcium, that involved 24,353 CRC cases and 30,650 controls, and 23 for that of VIT D, with a total of 19,076 cases and 36.746 controls included. For dietary calcium intake, the overall OR was 0.94 (95% CI 0.92-0.97), suggesting a reducing effect with a 6% decrease in CRC risk for every 300 mg of calcium ingested daily. Regarding vitamin D intake a global OR of 0.96 (95% CI 0.93-0.98) was observed, what means a 4% decrease in the risk of CRC per 100 IU/day of vitamin D. CONCLUSION: Higher dietary intakes of calcium and vitamin D are associated to a decreased risk of CRC.

[Discrimination and its relationship with risk behaviors and perceived health in spanish university students: a cross-sectional study.] / Discriminación y su relación con las conductas de riesgo y la salud percibida en estudiantes universitarios españoles: un estudio transversal.

OBJECTIVE: Discrimination during vital moments, such as the university period, can generate a high impact on people's behavior and health. The aim of this study was to analyze the possible association of discrimination with perceived health and with different risk behaviors, as well as to describe gender differences in Spanish university students. Discrimination during vital moments, such as college, can have a high impact on people's behavior and health. METHODS: A cross-sectional study was carried out with data from first-year university students from 11 Spanish universities (n=9,862). Discrimination, perceived health, alcohol consumption, smoking, consumption of illegal substances, leisure time connected to the Internet, risky sexual relations, family function, risk of mental health problems and risk of eating disorders were assessed. Prevalences with their 95% confidence intervals were obtained and for quantitative variables the mean and standard deviation were calculated. Odds ratios with 95% confidence intervals were calculated to determine the relationship between discrimination and the other variables. RESULTS: An association was found between discrimination and fair or poor perceived health (OR: 1.7; p=0.0001), consumption of illegal substances (OR: 1.3; p=0.002), problematic internet use (OR: 1.3; p=0.004), family dysfunction (OR: 1.8; p=0.0001), risk of mental health problems (OR: 1.9; p=0.0001) and eating disorders (OR: 1.5; p=0.0001). Regarding gender differences, higher prevalence of discrimination was observed in men with health status perceived as fair or worse (OR: 2.2; p=0.0001), family dysfunction (OR: 1.8; p=0.0001), risk of mental health problems (OR: 2.2; p=0.0001) and eating disorders (OR: 1.9; p=0.002). Women, apart from the previous variables, presented association of discrimination with consumption of illegal substances (OR: 1.3; p=0.005) and problematic internet use (OR: 1.4; p=0.002). CONCLUSIONS: The study findings underline that there is an association between discrimination and risk behaviors among Spanish university students. In turn, discrimination was associated with poor or fair perceived health, this relationship being similar in both men and women.

OBJETIVO: La discriminación durante los momentos vitales, como el periodo universitario, puede generar un alto impacto en la conducta y en el estado de salud de las personas. El estudio tuvo como objetivo analizar la posible asociación de la discriminación con la salud percibida y con distintas conductas de riesgo, así como describir las diferencias de género en estudiantes universitarios españoles. METODOS: Se realizó un estudio transversal con datos de estudiantes universitarios de primera matrícula de primer curso de 11 universidades españolas (n=9.862). Se valoró la discriminación, la salud percibida, el consumo de alcohol, el hábito tabáquico, el consumo de sustancias ilegales, el tiempo de ocio conectado a internet, la práctica de relaciones sexuales de riesgo, la función familiar, el riesgo de problemas de salud mental y el riesgo de trastornos de la conducta alimentaria. Se obtuvieron las prevalencias con sus intervalos de confianza al 95% y para las variables cuantitativas la media y desviación estándar. Se calcularon las Odds Ratio con los intervalos de confianza al 95% para conocer la relación entre la discriminación y las otras variables. RESULTADOS: Se encontró asociación entre la discriminación y una regular o mala salud percibida (OR: 1,7; p=0,0001), el consumo de sustancias ilegales (OR: 1,3; p=0,002), el uso problemático de internet (OR: 1,3; p=0,004), la disfunción familiar (OR: 1,8; p=0,0001), el riesgo de problemas de salud mental (OR: 1,9; p=0,0001) y de trastornos de la conducta alimentaria (OR: 1,5; p=0,0001). En cuanto a las diferencias de género, se apreciaron mayores prevalencias de discriminación en hombres con estado de salud percibida como regular o peor (OR: 2,2; p=0,0001), disfunción familiar (OR: 1,8; p=0,0001), riesgo de problemas de salud mental (OR: 2,2; p=0,0001) y de trastornos de la conducta alimentaria (OR: 1,9; p=0,002). Las mujeres, además de las variables anteriores, mostraron asociación de la discriminación con el consumo de sustancias ilegales (OR: 1,3; p=0,005) y el uso problemático de internet (OR: 1,4; p=0,002). CONCLUSIONES: Los hallazgos del estudio subrayan que existe asociación entre la discriminación y las conductas de riesgo de los estudiantes universitarios españoles. A su vez, la discriminación se asoció con una mala o regular salud percibida, siendo esta relación similar tanto en hombres como en mujeres.

Exposure to widespread drinking water chemicals, blood inflammation markers, and colorectal cancer.

BACKGROUND: Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water associated with colorectal cancer risk but mechanisms are not well understood. OBJECTIVES: We explored the association between exposure to THMs and nitrate in drinking water and inflammation markers, and the link with colorectal cancer risk. METHODS: A subset of 198 colorectal cancer cases and 205 controls from the multicase-control study MCC-Spain were included. Average concentration of THMs (chloroform, bromodichloromethane, dibromochloromethane, bromoform) and nitrate in tap water at the residence was estimated from age 18 until 2 years before the interview ("long term") and for a recent period (3 years before diagnosis). Serum levels of EGF, eotaxin, G-CSF, IL-17E, IL-1rA, IL-8, IP-10, MDC, MPO, periostin, VEGF, and C-reactive protein (CRP) were measured. We estimated the linear association between inflammation markers and exposure among controls, and the odds ratio of colorectal cancer associated with THM and nitrate exposure, and inflammation markers. A mediation analysis was conducted to identify inflammation markers in the pathway between THM/nitrate exposure and colorectal cancer. RESULTS: Serum concentrations of EGF, IL-8, IL-17E and eotaxin increased with recent residential levels of brominated THMs, chloroforom and/or total THM. No associations were observed for nitrate and for long-term residential THM levels. All residential exposures except chloroform were positively associated with colorectal cancer. Serum concentrations of VEGF and periostin were positively associated with colorectal cancer, while EGF was inversely associated. One protein-exposure combination (periostin-recent ingested brominated THMs) slightly mediated the association with colorectal cancer risk. DISCUSSION: Results suggest that estimated THM exposure is involved in inflammation processes. However, the study design was limited to stablish etiologically relevant associations between the protein levels and colorectal cancer risk. The lack of association between nitrate exposure and inflammation markers suggests other biological mechanisms are involved in the link with colorectal cancer.

Accuracy of Self-Reported Items for the Screening of Depression in the General Population.

INTRODUCTION: Though self-reported items (SRD, self-reported depression) are commonly used in health surveys and cohort studies, their metric properties as a depression indicator remain unclear. The aims were to evaluate the measurement properties of SRD using the Patient Health Questionnaire-8 (PHQ-8) as reference and to identify factors related to the agreement between both indicators. METHODS: Data from the European Health Interview Survey in Spain in 2014/2015 (n = 22,065) were analyzed. Two indicators of depression were considered: SRD based on two items yes/no (positive: both yes), and the PHQ-8 (positive ≥ 10). Socioeconomic factors and use of health services were considered as independent variables. The prevalence of depression, sensitivity, specificity, global agreement, and positive and negative predictive values (PPV and NPV) of SRDs were evaluated using the PHQ-8 as a reference. Logistic regression models were fitted to determine factors associated with the agreement between indicators. RESULTS: The prevalence of depression was lower when assessed with PHQ-8 (5.9%) than with SRD (7.7%). SRD sensitivity and PPV were moderate-low (52.9% and 40.4%, respectively) whereas global agreement, specificity, and NPV were high (92.7%, 95.1%, and 97.0%, respectively). Positive agreement was associated with marital status, country of birth, employment status, and social class. Negative agreement was related to all independent variables except country of birth. CONCLUSIONS: SRD items tend to overestimate the current prevalence of depression. While its use in health surveys and cohorts may be appropriate as a quick assessment of possible depression, due to their low sensitivity, its use in clinical contexts is questionable.

Association between Polyphenol Intake and Gastric Cancer Risk by Anatomic and Histologic Subtypes: MCC-Spain.

Several anticancer properties have been largely attributed to phenolics in in vivo and in vitro studies, but epidemiologic evidence is still scarce. Furthermore, some classes have not been studied in relation to gastric cancer (GC). The aim of this study was to assess the relationship between the intake of phenolic acids, stilbenes, and other phenolics and the risk of developing GC and its anatomical and histological subtypes. We used data from a multi-case-control study (MCC-Spain) obtained from different regions of Spain. We included 2700 controls and 329 GC cases. Odds ratios (ORs) were calculated using mixed effects logistic regression considering quartiles of phenolic intake. Our results showed an inverse association between stilbene and lignan intake and GC risk (ORQ4 vs. Q1 = 0.47; 95% CI: 0.32-0.69 and ORQ4 vs. Q1 = 0.53; 95% CI: 0.36-0.77, respectively). We found no overall association between total phenolic acid and other polyphenol class intake and GC risk. However, hydroxybenzaldehydes (ORQ4 vs. Q1 = 0.41; 95% CI: 0.28-0.61), hydroxycoumarins (ORQ4 vs. Q1 = 0.49; 95% CI: 0.34-0.71), and tyrosols (ORQ4 vs. Q1 = 0.56; 95% CI: 0.39-0.80) were inversely associated with GC risk. No differences were found in the analysis by anatomical or histological subtypes. In conclusion, a diet high in stilbenes, lignans, hydroxybenzaldehydes, hydroxycoumarins, and tyrosols was associated with a lower GC risk. Further prospective studies are needed to confirm our results.

Flavonoids and the Risk of Gastric Cancer: An Exploratory Case-Control Study in the MCC-Spain Study.

Several epidemiological studies have investigated the association between the dietary flavonoid intake and gastric cancer (GC) risk; however, the results remain inconclusive. Investigating the relationship between the different classes of flavonoids and the histological types and origin of GC can be of interest to the research community. We used data from a population-based multi-case control study (MCC-Spain) obtained from 12 different regions of Spain. 2700 controls and 329 GC cases were included in this study. Odds ratios (ORs) were calculated using the mixed effects logistic regression considering quartiles of flavonoid intakes and log2. Flavonoid intake was associated with a lower GC risk (ORlog2 = 0.76; 95% CI = 0.65-0.89; ORq4vsq1 = 0.60; 95%CI = 0.40-0.89; ptrend = 0.007). Inverse and statistically significant associations were observed with anthocyanidins, chalcones, dihydroflavonols and flavan-3-ols. The isoflavanoid intake was positively associated with higher cancer risk, but without reaching a statistical significance. In general, no differences were observed in the GC risk according to the location and histological type. The flavonoid intake seems to be a protective factor against GC within the MCC-study. This effect may vary depending on the flavonoid class but not by the histological type and location of the tumor. Broader studies with larger sample size and greater geographical variability are necessary.

Residential proximity to green spaces and breast cancer risk: The multicase-control study in Spain (MCC-Spain).

BACKGROUND: Breast cancer is the main cause of cancer mortality among women. Green spaces have been recently associated with reduced cancer mortality among women. Mechanisms explaining the beneficial effect of green spaces include increased levels of physical activity and reduced exposure to air pollution, which have been both associated with cancer development. OBJECTIVES: To investigate the associations between presence of urban green areas, presence of agricultural areas and surrounding greenness and risk of breast cancer, and to assess whether these associations are mediated by physical activity and/or air pollution levels. METHODS: We geocoded the current residence of 1129 breast cancer cases and 1619 controls recruited between 2008 and 2013 in ten provinces of Spain, as part of the MCC-Spain study. We assigned different indicators of exposure to green spaces in a buffer of 300 m, and in nested buffers of 100 m and 500 m around the residence: presence of urban green areas according to Urban Atlas, presence of agricultural areas according to CORINE Land Cover 2006, and surrounding greenness according to the average of the Normalized Difference Vegetation Index. We used logistic mixed-effects regression models with a random effect for hospital adjusting for potential confounders. We explored the effect of several potential effect modifiers. We assessed mediation effect by physical activity and levels of air pollution. RESULTS: Presence of urban green areas was associated with reduced risk of breast cancer after adjusting for age, socio-economic status at individual and at area level, education, and number of children [OR (95%CI) = 0.65 (0.49-0.86)]. There was evidence of a linear trend between distance to urban green areas and risk of breast cancer. On the contrary, presence of agricultural areas and surrounding greenness were associated with increased risk of breast cancer [adjusted OR (95%CI) = 1.33 (1.07-1.65) and adjusted OR (95%CI) = 1.27 (0.92-1.77), respectively]. None of the associations observed were mediated by levels of physical activity or levels or air pollution. CONCLUSIONS: The association between green spaces and risk of breast cancer is dependent on land-use. The confirmation of these results in other settings and the study of potential mechanisms for the associations observed are needed to advance the understanding on the potential effects of green spaces on health.

PGC-1α as a Biomarker of Physical Activity-Protective Effect on Colorectal Cancer.

Colorectal cancer is a significant public health concern. As a multistage and multifactorial disease, environmental and genetic factors interact at each stage of the process, and an individual's lifestyle also plays a relevant role. We set out to review the scientific evidence to study the need to investigate the role of the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) gene as a biomarker of the physical activity's (PA) effect on colorectal cancer. PA is a protective factor against colorectal cancer and usually increases the expression of PGC-1α This gene has pleiotropic roles and is the main regulator of mitochondrial functions. The development of colorectal cancer has been associated with mitochondrial dysfunction; in addition, alterations in this organelle are associated with colorectal cancer risk factors, such as obesity, decreased muscle mass, and the aging process. These are affected by PA acting, among other aspects, on insulin sensitivity and oxygen reactive species/redox balance. Therefore, this gene demands special attention in the understanding of its operation in the consensual protective effect of PA in colorectal cancer. A significant amount of indirect evidence points to PGC-1α as a potential biomarker in the PA-protective effect on colorectal cancer. The article focuses on the possible involvement of PGC-1α in the protective role that physical activity has on colorectal cancer. This is an important topic both in relation to advances in prevention of the development of this widespread disease and in its therapeutic treatment. We hope to generate an initial hypothesis for future studies associated with physical activity-related mechanisms that may be involved in the development or prevention of colorectal cancer. PGC-1α is highlighted because it is the main regulator of mitochondrial functions. This organelle, on one hand, is positively stimulated by physical activity; on the other hand, its dysfunction or reduction increases the probability of developing colorectal cancer. Therefore, we consider the compilation of existing information about the possible ways to understand the mechanisms of this gene to be highly relevant. This study is based on evidence of PGC-1α and physical activity, on PGC-1α and colorectal cancer, on colorectal cancer and physical activity/inactivity, and the absence of studies that have sought to relate all of these variables. Cancer Prev Res; 11(9); 523-34. ©2018 AACR.

Meat intake, methods and degrees of cooking and breast cancer risk in the MCC-Spain study.

OBJECTIVE: To analyse the relationship of the risk of breast cancer (BC) to meat intake, preference regarding degree of cooking ('doneness') and cooking methods, using data from a population-based case-control study (MCC-Spain). STUDY DESIGN: 1006 Histologically confirmed incident BC cases and 1370 controls were recruited in 10 Spanish provinces. Participants were 23-85 years old. They answered an epidemiological survey and a food frequency questionnaire. BC risk was assessed overall, by menopausal status and by pathological subtypes, using logistic and multinomial regression mixed models adjusted for known confounding factors and including province as a random effects term. MAIN OUTCOME MEASURES: Breast cancer and pathological subtype. RESULTS: High total intake of meat (ORQ4-Q1 (95% IC) = 1.39 (1.03-1.88)) was associated with increased BC risk among post-menopausal women. Similar results were found for processed/cured meat (ORQ4-Q1 (95% IC) = 1.47 (1.10-1.97)), and this association was particularly strong for triple-negative tumours (ER-, PR- and HER2-) (ORQ4-Q1 (95% IC) = 2.52 (1.15-5.49)). Intakes of well-done (ORwell-donevsrare (95% CI) = 1.62 (1.15-2.30)) and stewed (OR (95% CI) = 1.49 (1.20-1.84)) red meat were associated with increased BC risk, with a high risk observed for HR+ tumours (ER+/PR+ and HER2-). Pan-fried/bread-coated fried white meat, but not doneness preference, was associated with an increased BC risk for all women (OR (95% CI) = 1.38 (1.14-1.65)), with a stronger association for pre-menopausal women (OR (95% CI) = 1.78 (1.29-2.46)). CONCLUSION: The risk of developing BC could be reduced by moderating the consumption of well-done or stewed red meat, pan-fried/bread-coated fried white meat and, especially, processed/cured meat.

Risk of breast cancer and residential proximity to industrial installations: New findings from a multicase-control study (MCC-Spain).

Breast cancer is the most frequent tumor in women worldwide, although well-established risk factors account for 53%-55% of cases. Therefore, other risk factors, including environmental exposures, may explain the remaining variation. Our objective was to assess the relationship between risk of breast cancer and residential proximity to industries, according to categories of industrial groups and specific pollutants released, in the context of a population-based multicase-control study of incident cancer carried out in Spain (MCC-Spain). Using the current residence of cases and controls, this study was restricted to small administrative divisions, including both breast cancer cases (452) and controls (1511) in the 10 geographical areas recruiting breast cancer cases. Distances were calculated from the respective woman's residences to the 116 industries located in the study area. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (between 1 km and 3 km) to industrial plants, adjusting for matching variables and other confounders. Excess risk (OR; 95%CI) of breast cancer was found near industries overall (1.30; 1.00-1.69 at 3 km), particularly organic chemical industry (2.12; 1.20-3.76 at 2.5 km), food/beverage sector (1.87; 1.26-2.78 at 3 km), ceramic (4.71; 1.62-13.66 at 1.5 km), surface treatment with organic solvents (2.00; 1.23-3.24 at 3 km), and surface treatment of plastic and metals (1.51; 1.06-2.14 at 3 km). By pollutants, the excess risk (OR; 95%CI) was detected near industries releasing pesticides (2.09; 1.14-3.82 at 2 km), and dichloromethane (2.09; 1.28-3.40 at 3 km). Our results suggest a possible increased risk of breast cancer in women living near specific industrial plants and support the need for more detailed exposure assessment of certain agents released by these plants.

Long-term exposure to trihalomethanes in drinking water and breast cancer in the Spanish multicase-control study on cancer (MCC-SPAIN).

BACKGROUND: Exposure to trihalomethanes (THMs) in drinking water has consistently been associated with an increased risk of bladder cancer, but evidence on other cancers including the breast is very limited. OBJECTIVES: We assessed long-term exposure to THMs to evaluate the association with female breast cancer (BC) risk. METHODS: A multi case-control study was conducted in Spain from 2008 to 2013. We included 1003 incident BC cases (women 20-85years old) recruited from 14 hospitals and 1458 population controls. Subjects were interviewed to ascertain residential histories and major recognized risk factors for BC. Mean residential levels of chloroform, brominated THMs (Br-THMs) and the sum of both as total THM (TTHMs) during the adult-lifetime were calculated. RESULTS: Mean adult-lifetime residential levels ranged from 0.8 to 145.7µg/L for TTHM (median=30.8), from 0.2 to 62.4µg/L for chloroform (median=19.7) and from 0.3 to 126.0µg/L for Br-THMs (median=9.7). Adult-lifetime residential chloroform was associated with BC (adjusted OR=1.47; 95%CI=1.05, 2.06 for the highest (>24µg/L) vs. lowest (<8µg/L) quartile; p-trend=0.024). No association was detected for residential Br-THMs (OR=0.91; 95%CI=0.68, 1.23 for >31µg/L vs. <6µg/L) or TTHMs (OR=1.14; 95%CI=0.83, 1.57 for >48µg/L vs. <22µg/L). CONCLUSIONS: At common levels in Europe, long-term residential total THMs were not related to female breast cancer. A moderate association with chloroform was suggested at the highest exposure category. This large epidemiological study with extensive exposure assessment overcomes several limitations of previous studies but further studies are needed to confirm these results.

Post-colonoscopy colorectal cancer: Characteristics and predictive factors. / Cáncer colorrectal poscolonoscopia: características y factores predictivos.

INTRODUCTION AND AIMS: A high quality colonoscopy is key in preventing colorectal cancer, but the risk of colorectal cancer (CRC) exists. The aims of the study were to investigate the incidence, characteristics and predictive factors of post-colonoscopy colorectal cancer (PCCRC). MATERIAL AND METHOD: A retrospective and prospective observational study was designed. A population undergoing colonoscopy between 1-01-1997 and 31-12-2014 was included. We analysed demographic variables, characteristics of the diagnostic colonoscopy of CRC, of the previous ones and the lesions found in them. To compare the PCCRC group versus the CRC group without previous colonoscopy, the Student's t-test and multiple logistic regression were used to determine predictive factors of PCCRC (SPSS® 15). The statistical significance was P<.05. RESULTS: A total of 56,984 colonoscopies, 1,977 CRC and 132 patients (mean 70.8 years old, 56.8% male) with at least one colonoscopy in 10 years before were registered (PCCRC). Seventy and a half percent of the previous colonoscopies were completed and 63.7% had an adequate bowel preparation. Predictive factors of PCCRC were personal history of polyps (OR 35.01; 95% CI 11.1-110.8; P<.001), previous CRC (OR 176.64; 95% CI 51.5-606.1); P<.001), family history of CRC (OR 3.14; 95% CI 1.5-6.4); P=.002) and proximal CRC (OR 3.15; 95% CI 2.1-4.9; P<.001). CONCLUSIONS: PCCRC rate in 10 years was 6.7%. An adequate follow-up and a high-quality colonoscopy could prevent PCCRC, especially in patients with risk factors.

Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study.

Colorectal cancer (CRC) screening of the average risk population is only indicated according to age. We aim to elaborate a model to stratify the risk of CRC by incorporating environmental data and single nucleotide polymorphisms (SNP). The MCC-Spain case-control study included 1336 CRC cases and 2744 controls. Subjects were interviewed on lifestyle factors, family and medical history. Twenty-one CRC susceptibility SNPs were genotyped. The environmental risk model, which included alcohol consumption, obesity, physical activity, red meat and vegetable consumption, and nonsteroidal anti-inflammatory drug use, contributed to CRC with an average per factor OR of 1.36 (95% CI 1.27 to 1.45). Family history of CRC contributed an OR of 2.25 (95% CI 1.87 to 2.72), and each additional SNP contributed an OR of 1.07 (95% CI 1.04 to 1.10). The risk of subjects with more than 25 risk alleles (5th quintile) was 82% higher (OR 1.82, 95% CI 1.11 to 2.98) than subjects with less than 19 alleles (1st quintile). This risk model, with an AUROC curve of 0.63 (95% CI 0.60 to 0.66), could be useful to stratify individuals. Environmental factors had more weight than the genetic score, which should be considered to encourage patients to achieve a healthier lifestyle.

Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case-Control Study in Spain and Italy.

BACKGROUND: Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent. OBJECTIVES: We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer. METHODS: A multicenter case-control study was conducted in Spain and Italy in 2008-2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, type of water consumed in each residence, frequency and duration of showering/bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant's residential tap water (micrograms/liter; from age 18 to 2 years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (micrograms/day). RESULTS: We analyzed 2,047 cases and 3,718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0-174), 17 (0-63), and 9 (0-145) µg/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR = 0.92, 95% CI: 0.66, 1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR = 0.31, 95% CI: 0.24, 0.41 for highest vs. lowest quartile). Brominated THM concentrations showed a positive association among men in the highest versus the lowest quartile (OR = 1.43, 95% CI: 0.83, 2.46). Patterns of association were similar for estimated average THM ingestion through residential water consumption. CONCLUSIONS: We did not find clear evidence of an association between detailed estimates of lifetime total THM exposure and colorectal cancer in our large case-control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings should be confirmed in other study populations. Citation: Villanueva CM, Gracia-Lavedan E, Bosetti C, Righi E, Molina AJ, Martín V, Boldo E, Aragonés N, Perez-Gomez B, Pollan M, Gomez Acebo I, Altzibar JM, Jiménez Zabala A, Ardanaz E, Peiró R, Tardón A, Chirlaque MD, Tavani A, Polesel J, Serraino D, Pisa F, Castaño-Vinyals G, Espinosa A, Espejo-Herrera N, Palau M, Moreno V, La Vecchia C, Aggazzotti G, Nieuwenhuijsen MJ, Kogevinas M. 2017. Colorectal cancer and long-term exposure to trihalomethanes in drinking water: a multicenter case---control study in Spain and Italy. Environ Health Perspect 125:56-65; http://dx.doi.org/10.1289/EHP155.

Problematic Internet Use in University Students: associated factors and differences of gender.

The aim of this paper is to make a descriptive analysis of Problematic Internet Use in college students, evaluating the possible association with health problems and addictive behaviors, as well as gender differences in user types. A total of 2,780 students participated in the study between 2011 and 2014, 29% of them being males (age 20.8 ± 5.1 years) and 71% females (age 20.3 ± 4.4 years). The prevalence of Problematic Internet Use (PIU) assessed by the Internet Addiction Test was 6.08%. Being under 21 years of age and studying for degrees in subjects other than the health sciences were associated factors with a higher frequency of this problem, no differences by gender or type of address were found. The results show a significant association with some health problems (migraines, back pain, excess weight or obesity, insufficient rest), psychological aspects (risk of eating disorders, risk of mental disorder, depression), family problems and discrimination; with no associations with substance use (alcohol, cannabis or tobacco) being found. Concerning the time of Internet use, weekly hours were significantly higher in women than in men, both the total time as for leisure. The analysis of the profile use in problematic users revealed that males are related to aspects of entertainment such as games or shopping online and females are related to aspects of socialization, such as chats and social networks.

El objetivo del presente trabajo es realizar un análisis descriptivo del uso problemático de Internet en estudiantes universitarios, evaluando la posible asociación con problemas de salud y conductas adictivas, así como diferencias de género en los tipos utilización. Un total de 2780 alumnos participaron en el estudio entre los años 2011 ­ 2014, siendo un 29% varones (edad 20.8 ± 5.1 años) y un 71% mujeres (edad de 20.3 ± 4.4 años). La prevalencia de uso problemático de Internet evaluada mediante el Internet Addiction Test fue del 6.08%. Ser menor de 21 años y cursar titulaciones diferentes a ciencias de la salud fueron factores asociados a una mayor frecuencia de este problema, no existiendo diferencias en función del sexo o tipo de domicilio. Los resultados muestran una asociación significativa con algunos problemas de salud (migrañas, dolor lumbar, sobrepeso u obesidad, descanso insuficiente), aspectos psicológicos (riesgo de trastornos de la conducta alimentaria, riesgo de trastorno mental, depresión), problemas familiares y discriminación; no encontrándose asociaciones con consumo de sustancias adictivas (alcohol, tabaco o cannabis). Respecto al tiempo de uso de Internet, las horas de conexión semanales fueron significativamente mayores en las mujeres que en los hombres, tanto en el tiempo total como por motivos de ocio. El análisis del perfil de utilización en usuarios problemáticos reveló que los varones se relacionan más con aspectos de ocio como los juegos o las compras online y las mujeres con aspectos de socialización, como el chat o las redes sociales.

Características clínicas, anatomopatológicas y moleculares en casos de cáncer colorrectal según localización tumoral y grado de diferenciación / Clinical, anatomopathological and molecular characteristics of colorectal cancer by tumor location and degree of differentiation

Objetivos: El cáncer colorrectal (CCR) presenta elevada incidencia y mortalidad con diferentes tendencias según localización anatómica y otras características anatomopatológicas que parecen vinculadas a cambios tanto a la exposición a factores de riesgo como al diagnóstico siendo esencial una adecuada filiación tumoral para valorar el efecto de dichos factores en la aparición, diagnóstico y progresión de la enfermedad. El objetivo fue describir las características clínicas y anatomopatológicas de pacientes diagnosticados de CCR en el Área de Salud de León en función de la localización tumoral y del grado de diferenciación. Métodos: Se estudió una serie de 408 casos de entre 25 y 85 años con diagnóstico confirmado de CCR, recogiéndose información de características clínicas y anatomopatológicas y de los biomarcadores analizados en la rutina clínica. Se realizó análisis univariable y bivariable según el grado de diferenciación y la localización tumoral. Resultados: El tamano tumoral disminuye desde colon proximal a recto (Colon Proximal = 5,13 cm: Colon Distal = 4,09cm: Recto = 3,17cm; p< 0,001) siendo el TNM también mayor en zonas proximales. Los adenocarcinomas mucinosos son más frecuentes en tumores pobremente diferenciados que en bien diferenciados (23,1% vs 5,5%). Las invasiones linfática, venosa y peritumoral son más frecuentes con menor grado de diferenciación. Conclusiones: La distribución del estadio tumoral en función de la localización tiene estadios TNM más avanzados en zonas proximales, lo que podría asociarse a una menor detección precoz en dichos casos. La asociación entre invasión venosa y linfática con el grado de diferenciación es poco conocida requiriéndose estudios que aclaren su posible interés pronóstico.

Aims: Colorectal cancer (CRC) has a high incidence and mortality, with different patterns depending on anatomical location and other pathological characteristics that appear linked to changes in exposure risk factors exposure as well as the diagnosis. All these make it essential to determine the source of the tumour to properly assess the effect of these factors in the development, diagnosis and progression of the disease. The aim was to describe the clinical and anatomical-pathological characteristics of patients diagnosed with CRC in the Health Area of Leon (ASL) based on their location and degree of tumour differentiation. Methods: Information was collected on the clinical and pathological characteristics, including biological markers analysed in clinical routine of 408 patients between 25 and 85 years with a confirmed diagnosis of CRC, and residents in ASL at least six months before diagnosis. Univariate and bivariate analyses were performed according to the degree of differentiation and tumour location. Results: Tumour size decreases from the colon to the rectum from location decline proximal colon to the rectum (Proximal Colon = 5.13cm; Distal Colon = 4.09cm; Rectum = 3.17cm, P< 0.001), with the TNM stage also being higher in proximal areas. Mucinous adenocarcinomas are more frequent in poorly differentiated than in well differentiated tumours (23.1% vs 5.5%). Lymphatic, venous and peri-tumour invasions are more common in poorly differentiated tumours. Conclusions: The distribution in accordance with the location has more advanced TNM stages in the proximal areas, which could be related to the poorer early diagnosis in proximal areas. The association between venous and lymphatic invasion with the degree of differentiation is poorly understood, and requires studies to clarify their possible prognostic interest.

Hormonal contraception and postmenopausal hormone therapy in Spain: time trends and patterns of use.

OBJECTIVE: This study aims to describe time trends in and patterns of use of hormonal contraception and postmenopausal hormone therapy and to identify factors associated with their use among Spanish women. METHODS: We performed a cross-sectional analysis using data from 1,954 population controls (aged 24-85 y) in 12 provinces of Spain who were enrolled in the Multi Case-Control Spain study (2007-2013). Data were collected from a questionnaire conducted face-to-face by trained personnel. We collected information on sociodemographic factors, lifestyle, sleep patterns, reproductive history, and occupational history. RESULTS: Overall, 48.5% of Spanish women reported ever use of hormonal contraception, and 9.8% of women in the postmenopausal group reported use of postmenopausal hormone therapy. Younger cohorts used hormonal contraception for a longer period, whereas postmenopausal hormone therapy use dramatically dropped in the 2000s. Women with higher education levels (including education of partners) and smoking history were the most probable users of hormonal contraception, whereas inverse associations were observed among housewives, obese women, and nulliparous women. Postmenopausal hormone therapy use was associated with a surgical or therapeutic cause of menopause and with occupational history of rotating shifts. CONCLUSIONS: In this Spanish population, several demographic, lifestyle, occupational, and reproductive factors are associated with use of hormonal compounds. Characterizing hormonal users and monitoring trends in the use of these hormonal compounds are essential from a public health perspective.