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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. http://dx.doi.org/ 10.1289/EHP155., Introduction Colorectal cancer represents nearly 10% of global cancer incidence, with increasing rates over the last decades (Bosman et al. 2014). Intake of total energy, red and processed meat, and [...]

BACKGROUND: Ingested nitrate leads to endogenous formation of V-nitroso compounds that are breast carcinogens in animals, but human evidence is limited. OBJECTIVE: We evaluated ingested nitrate as a risk factor for breast cancer (BC) in a multicase--control study. METHODS: Hospital-based incident BC cases and population-based controls were recruited in eight Spanish regions in 2008-2013; participants provided residential and water consumption from 18 years of age and information on known BC risk factors. Long-term nitrate levels (1940-2010) were estimated and linked with residential histories and water consumption to calculate waterborne ingested nitrate (milligrams/day). Dietary ingested nitrate (milligrams/day) was calculated using food frequency questionnaires and published dietary nitrate contents. Interactions with endogenous nitrosation factors and other variables were evaluated. A total of 1,245 cases and 1,520 controls were included in the statistical analysis. RESULTS: Among the study regions, average [+ or -] SD waterborne ingested nitrate ranged from 2.9 [+ or -] 1.9 to 13.5 [+ or -] 7.5 mg/day, and dietary ingested nitrate ranged from 88.5 [+ or -] 48.7 to 154 [+ or -] 87.8 mg/day. Waterborne ingested nitrate was not associated with BC overall, but among postmenopausal women, those with both high nitrate (> 6 vs. < 2.6 mg/day) and high red meat intake (> 20 vs. < 20 g/day) were more likely to be cases than women with low nitrate and low red meat intake (adjusted odds ratio = 1.64; 95% confidence interval: 1.08, 2.49; overall interaction p-value = 0.17). No association was found with dietary nitrate. CONCLUSIONS: Waterborne ingested nitrate was associated with BC only among postmenopausal women with high red meat consumption. Dietary nitrate was not associated with BC regardless of the animal or vegetable source or of menopausal status. http://dx.doi.org/10.1289/ehp.1510334, Introduction Breast cancer (BC) is the leading cause of cancer mortality and is the most common cancer among women worldwide. In Spain, 25,215 new cases are diagnosed annually (Ferlay et [...]

Abstract Background Records kept as a result of the implementation of Integrated Pollution Prevention and Control (IPPC) and the European Pollutant Release and Transfer Register (E-PRTR) constitute a public inventory of industries, created by the European Commission, which is a valuable resource for monitoring industrial pollution. Our objective is to ascertain whether there might be excess colorectal cancer mortality among populations residing in the vicinity of Spanish industrial installations that are governed by the IPPC Directive and E-PRTR Regulation and report their emissions to air. Methods An ecological study was designed to examine colorectal cancer mortality at a municipal level (8098 Spanish towns), over the period 1997–2006. We conducted an exploratory "near vs. far" analysis to estimate the relative risks (RR) of towns situated at a distance of less than 2 km from industrial installations. The analysis was repeated for each of the 24 industrial groups. RR and their 95% credible/confidence intervals (95%CI) were estimated on the basis of Poisson regression models, using two types of modelling: a) the conditional autoregressive Bayesian model proposed by Besag, York and Mollié, with explanatory variables; and b) a mixed regression model. Integrated nested Laplace approximations were used as a Bayesian inference tool. Results Statistically significant RRs were detected in the vicinity of mining industry (RR 1.258; 95%CI 1.082 - 1.463), paper and wood production (RR 1.071; 95%CI 1.007 – 1.140), food and beverage sector (RR 1.069; 95%CI 1.029 - 1.111), metal production and processing installations (RR 1.065; 95% CI 1.011 – 1.123) and ceramics (RR 1.050 ; 95%CI 1.004 – 1.099). Conclusions Given the exploratory nature of this study, it would seem advisable to check in other countries or with other designs, if the proximity of industries that emit pollutants into the air could be an added risk factor for colorectal cancer mortality. Nevertheless, some of the differences between men and women observed in the analyses of the industrial groups suggest that there may be a component of occupational exposure, little-studied in the case of cancers of the digestive system.

Abstract Background Emissions from refineries include a wide range of substances, such as chrome, lead, nickel, zinc, arsenic, cadmium, benzene, dioxins and furans, all of which are recognized by the International Agency for Research on Cancer (IARC) as carcinogens. Various studies have shown an association between non-Hodgkin lymphoma (NHL) and residence in the vicinity of industrial areas; however, evidence of specific association between refineries and residence in the vicinity has been suggested but not yet established. The aim of this study is to investigate potential links between environmental exposure to emissions from refineries and non-Hodgkin lymphoma mortality in Spain. The spatial distribution of NHL in Spain has an unusual pattern with regions some showing higher risk than others. Methods We designed an analysis of matched geographical areas to examine non-Hodgkin lymphoma mortality in the vicinity of the 10 refineries sited in Spain over the period 1997-2006. Population exposure to refineries was estimated on the basis of distance from town of residence to the facility in a 10 km buffer. We defined 10 km radius areas to perform the matching, accounting for population density, level of industrialization and socio-demographic factors of the area using principal components analysis. For the matched towns we evaluated the risk of NHL mortality associated with residence in the vicinity of the refineries and with different regions using mixed Poisson models. Then we study the residuals to assess a possible risk trend with distance. Results Relative risks (RRs) associated with exposure showed similar values for women and for men, 1.09 (0.97-1.24) and 1.12 (0.99-1.27). RRs for two regions were statistically significant: Canary Islands showed an excess of risk of 1.35 (1.05-1.72) for women and 1.50 (1.18-1.92) for men, whilst Galicia showed an excess of risk of 1.35 (1.04-1.75) for men, but not significant excess for women. Conclusions The results suggest a possible increased risk of NHL mortality among populations residing in the vicinity of refineries; however, a potential distance trend has not been shown. Regional effects in the Canary Islands and Galicia are significantly greater than the regional average.

Abstract Background Gastric cancer is the second leading cause of oncologic death worldwide. One of the most noteworthy characteristics of this tumor's epidemiology is the marked decline reported in its incidence and mortality in almost every part of the globe in recent decades. This study sought to describe gastric cancer mortality time trends in Spain's regions for both sexes. Methods Mortality data for the period 1976 through 2005 were obtained from the Spanish National Statistics Institute. Cases were identified using the International Classification of Diseases 9th and 10th revision (codes 151 and C16, respectively). Crude and standardized mortality rates were calculated by geographic area, sex, and five-year period. Joinpoint regression analyses were performed to ascertain whether changes in gastric cancer mortality trends had occurred, and to estimate the annual percent change by sex and geographic area. Results Gastric cancer mortality decreased across the study period, with the downward trend being most pronounced in women and in certain regions situated in the interior and north of mainland Spain. Across the study period, there was an overall decrease of 2.90% per annum among men and 3.65% per annum among women. Generally, regions in which the rate of decline was sharpest were those that had initially registered the highest rates. However, the rate of decline was not constant throughout the study period: joinpoint analysis detected a shift in trend for both sexes in the early 1980s. Conclusion Gastric cancer mortality displayed in both sexes a downward trend during the study period, both nationally and regionally. The different trend in rates in the respective geographic areas translated as greater regional homogeneity in gastric cancer mortality by the end of the study period. In contrast, rates in women fell more than did those in men. The increasing differences between the sexes could indicate that some risk factors may be modifying the sex-specific pattern of this tumor.

Abstract Background Gastric cancer is decreasing in most countries. While socioeconomic development is the main factor to which this decline has been attributed, enormous differences among countries and within regions are still observed, with the main contributing factors remaining elusive. This study describes the geographic distribution of gastric cancer mortality at a municipal level in Spain, from 1994-2003. Methods Smoothed relative risks of stomach cancer mortality were obtained, using the Besag-York-Molliè autoregressive spatial model. Maps depicting relative risk (RR) estimates and posterior probabilities of RR being greater than 1 were plotted. Results From 1994-2003, 62184 gastric cancer deaths were registered in Spain (7 percent of all deaths due to malignant tumors). The geographic pattern was similar for both sexes. RRs displayed a south-north and coast-inland gradient, with lower risks being observed in Andalusia, the Mediterranean coastline, the Balearic and Canary Islands and the Cantabrian seaboard. The highest risk was concentrated along the west coast of Galicia, broad areas of the Castile & Leon Autonomous community, the province of Cáceres in Extremadura, Lleida and other areas of Catalonia. Conclusion In Spain, risk of gastric cancer mortality displays a striking geographic distribution. With some differences, this persistent and unique pattern is similar across the sexes, suggesting the implication of environmental exposures from sources, such as diet or ground water, which could affect both sexes and delimited geographic areas. Also, the higher sex-ratios found in some areas with high risk of smoking-related cancer mortality in males support the role of tobacco in gastric cancer etiology.

Abstract Background The European Pollutant Emission Register in Spain (EPER-Spain) is a public inventory of pollutant industries created by decision of the European Union. The location of these industries is geocoded and the first published data correspond to 2001. Publication of these data will allow for quantification of the effect of proximity to one or more such plant on cancer and all-cause mortality observed in nearby towns. However, as errors have been detected in the geocoding of many of the pollutant foci shown in the EPER, it was decided that a validation study should be conducted into the accuracy of these co-ordinates. EPER-Spain geographic co-ordinates were drawn from the European Environment Agency (EEA) server and the Spanish Ministry of the Environment (MOE). The Farm Plot Geographic Information System (Sistema de Información Geográfica de Parcelas Agrícolas) (SIGPAC) enables orthophotos (digitalized aerial images) of any territorial point across Spain to be obtained. Through a search of co-ordinates in the SIGPAC, all the industrial foci (except farms) were located. The quality criteria used to ascertain possible errors in industrial location were high, medium and low quality, where industries were situated at a distance of less than 500 metres, more than 500 metres but less than 1 kilometre, and more than 1 kilometre from their real locations, respectively. Results Insofar as initial registry quality was concerned, 84% of industrial complexes were inaccurately positioned (low quality) according to EEA data versus 60% for Spanish MOE data. The distribution of the distances between the original and corrected co-ordinates for each of the industries on the registry revealed that the median error was 2.55 kilometres for Spain overall (according to EEA data). The Autonomous Regions that displayed most errors in industrial geocoding were Murcia, Canary Islands, Andalusia and Madrid. Correct co-ordinates were successfully allocated to 100% of EPER-Spain industries. Conclusion Knowing the exact location of pollutant foci is vital to obtain reliable and valid conclusions in any study where distance to the focus is a decisive factor, as in the case of the consequences of industrial pollution on the health of neighbouring populations.

Abstract Background Toxic substances released into the environment (to both air and water) by many types of industries might be related with the occurrence of some malignant tumours and other diseases. The publication of the EPER (European Pollutant Emission Register) Spanish data allows to investigate the presence of geographical mortality patterns related to industrial pollution. The aim of this paper is to describe industrial air and water pollution in Spain in 2001, broken down by activity group and specific pollutant, and to plot maps depicting emissions of carcinogenic substances. Methods All information on industrial pollution discharge in 2001 was drawn from EPER-Spain public records provided by the European Commission server. We described the distribution of the number of industries and amounts discharged for each pollutant, as well as emission by pollutant group and the industrial activities associated with each pollutant. Maps of Spain were drawn up, with UTM coordinates being used to plot pollutant foci, and circles with an area proportional to the emission to depict pollution emission values. Results The EPER-Spain contained information on 1,437 industrial installations. The industrial plants that discharge pollutant substances into air and water above the pollutant-specific EPER threshold were mainly situated in the Autonomous Regions of Aragon, Andalusia and Catalonia and in Catalonia, the Basque Country and Andalusia respectively. Pollution released in 2001 into air approached 158 million Mt. Emissions into water were over 8 million Mt. Conclusion A few single industrial plants are responsible for the highest percentage of emissions, thus rendering monitoring of their possible health impact on the surrounding population that much simpler. Among European countries Spain is the leading polluter in almost one third of all EPER-registered pollutant substances released into the air and ranks among the top three leading polluters in two-thirds of all such substances. Information obtained through publication of EPER data means that the possible consequences of reported pollutant foci on the health of neighbouring populations can now be studied.

Abstract Background Oesophageal carcinoma is one of the most common cancers worldwide. Its incidence and mortality rates show a wide geographical variation at a world and regional level. Geographic mapping of age-standardized, cause-specific death rates at a municipal level could be a helpful and powerful tool for providing clues leading to a better understanding of its aetiology. Methods This study sought to describe the geographic distribution of oesophageal cancer mortality for Spain's 8077 towns, using the autoregressive spatial model proposed by Besag, York and Mollié. Maps were plotted, depicting standardised mortality ratios, smoothed relative risk (RR) estimates, and the spatial pattern of the posterior probability of RR being greater than 1. Results Important differences associated with area of residence were observed in risk of dying from oesophageal cancer in Spain during the study period (1989–1998). Among men, excess risk appeared across the north of the country, along a band spanning the length of the Cantabrian coastline, Navarre, the north of Castile & León and the north-west of La Rioja. Excess risk was likewise observed in the provinces of Cadiz and part of Seville in Andalusia, the islands of Tenerife and Gran Canaria, and some towns in the Barcelona and Gerona areas. Among women, there was a noteworthy absence of risk along the mid-section of the Cantabrian seaboard, and increases in mortality, not observed for men, in the west of Extremadura and south-east of Andalusia. Conclusion These major gender- and area-related geographical differences in risk would seem to reflect differences in the prevalence of some well-established and modifiable risk factors, including smoking, alcohol consumption, obesity and diet. In addition, excess risks were in evidence for both sexes in some areas, possibly suggesting the implication of certain local environmental or socio-cultural factors. From a public health standpoint, small-area studies could be very useful for identifying locations where epidemiological research and intervention measures ought to receive priority, given the potential for reducing risk in certain places.