Meat Intake, Cooking Methods, Doneness Preferences and Risk of Gastric Adenocarcinoma in the MCC-Spain Study.

BACKGROUND: The association of meat intake with gastric adenocarcinoma is controversial. We examined the relation between white, red, and processed meat intake and gastric adenocarcinoma, considering doneness preference and cooking methods, by histological subtype and anatomical subsite. METHODS: MCC-Spain is a multicase-control study that included 286 incident gastric adenocarcinoma cases and 2993 controls who answered a food-frequency questionnaire. The association of gastric adenocarcinoma with meat intake, doneness preference and cooking methods was assessed using binary multivariate logistic regression mixed models and a possible interaction with sex was considered. Multinomial logistic regression models were used to estimate risk by tumor subsite (cardia vs. non-cardia) and subtype (intestinal vs. diffuse). Sensitivity analyses were conducted comparing models with and without data on Helicobacter pylori infection. RESULTS: The intake of red and processed meat increased gastric adenocarcinoma risk (OR for one serving/week increase (95% CI) = 1.11 (1.02;1.20) and 1.04 (1.00;1.08), respectively), specifically among men and for non-cardia and intestinal gastric adenocarcinoma. Those who consume well done white or red meat showed higher risk of non-cardia (white: RRR = 1.57 (1.14;2.16); red: RRR = 1.42 (1.00;2.02)) and intestinal tumors (white: RRR = 1.69 (1.10;2.59); red: RRR = 1.61 (1.02;2.53)) than those with a preference for rare/medium doneness. Stewing and griddling/barbequing red and white meat, and oven baking white meat, seemed to be the cooking methods with the greatest effect over gastric adenocarcinoma. The reported associations remained similar after considering Helicobacter pylori seropositivity. CONCLUSIONS: Reducing red and processed meat intake could decrease gastric adenocarcinoma risk, especially for intestinal and non-cardia tumors. Meat cooking practices could modify the risk of some gastric cancer subtypes.

Association between proximity to industrial chemical installations and cancer mortality in Spain.

It is likely that pollution from chemical facilities will affect the health of any exposed population; however, the majority of scientific evidence available has focused on occupational exposure rather than environmental. Consequently, this study assessed whether there could have been an excess of cancer-related mortality associated with environmental exposure to pollution from chemical installations - for populations residing in municipalities in the vicinity of chemical industries. To this end, we designed an ecological study which assessed municipal mortality due to 32 types of cancer in the period from 1999 to 2008. The exposure to pollution was estimated using distance from the facilities to the centroid of the municipality as a proxy for exposure. In order to assess any increased cancer mortality risk in municipalities potentially exposed to chemical facilities pollution (situated at a distance of ≤5 km from a chemical installation), we employed Bayesian Hierarchical Poisson Regression Models. This included two Bayesian inference methods: Integrated Nested Laplace Approximations (INLA) and Markov Chain Monte Carlo (MCMC, for validation). The reference category consisted of municipalities beyond the 5 km limit. We found higher mortality risk (relative risk, RR; estimated by INLA, 95% credible interval, 95%CrI) for both sexes for colorectal (RR, 1.09; 95%CrI, 1.05-1.15), gallbladder (1.14; 1.03-1.27), and ovarian cancers (1.10; 1.02-1.20) associated with organic chemical installations. Notably, pleural cancer (2.27; 1.49-3.41) in both sexes was related to fertilizer facilities. Associations were found for women, specifically for ovarian (1.11; 1.01-1.22) and breast cancers (1.06; 1.00-1.13) in the proximity of explosives/pyrotechnics installations; increased breast cancer mortality risk (1.10; 1.03-1.18) was associated with proximity to inorganic chemical installations. The results suggest that environmental exposure to pollutants from some types of chemical facilities may be associated with increased mortality from several different types of cancer.

Childhood leukaemia risk and residential proximity to busy roads.

BACKGROUND: Current evidence suggests that childhood leukaemia can be associated with residential traffic exposure; nevertheless, more results are needed to support this conclusion. OBJECTIVES: To ascertain the possible effects of residential proximity to road traffic on childhood leukaemia, taking into account traffic density, road proximity and the type of leukaemia (acute lymphoid leukaemia or acute myeloid leukaemia). METHODS: We conducted a population-based case-control study of childhood leukaemia in Spain, covering the period 1990-2011. It included 1061 incidence cases gathered from the Spanish National Childhood Cancer Registry and those Autonomous Regions with 100% coverage, and 6447 controls, individually matched by year of birth, sex and autonomous region of residence. Distances were computed from the respective participant's residential locations to the different types of roads and four different buffers. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs), were calculated for four different categories of distance to roads. RESULTS: Cases of childhood leukaemia had more than three-fold increased odds of living at <50 m of the busiest motorways compared to controls (OR = 2.90; 95%CI = 1.30-6.49). The estimates for acute lymphoid leukaemia (ALL) were slightly higher (OR = 2.95; 95%CI = 1.22-7.14), while estimates for cases with the same address at birth and at diagnosis were lower (OR = 2.40; 95%CI = 0.70-8.30). CONCLUSIONS: Our study agrees with the literature and furnishes some evidence that living near a busy motorway could be a risk factor for childhood leukaemia.

Impact of 2 Successive Smoking Bans on Hospital Admissions for Cardiovascular Diseases in Spain.

INTRODUCTION AND OBJECTIVES: To evaluate the impact of 2 smoking bans enacted in 2006 (partial ban) and 2011 (comprehensive ban) on hospitalizations for cardiovascular disease in the Spanish adult population. METHODS: The study was performed in 14 provinces in Spain. Hospital admission records were collected for acute myocardial infarction (AMI), ischemic heart disease (IHD), and cerebrovascular disease (CVD) in patients aged ≥ 18 years from 2003 through 2012. We estimated immediate and 1-year effects with segmented-linear models. The coefficients for each province were combined using random-effects multivariate meta-analysis models. RESULTS: Overall, changes in admission rates immediately following the implementation of the partial ban and 1 year later were -1.8% and +1.2% for AMI, +0.1 and +0.4% for IHD, and +1.0% and +2.8% for CVD (P>.05). After the comprehensive ban, immediate changes were -2.3% for AMI, -2.6% for IHD, and -0.8% for CVD (P>.05), only to return to precomprehensive ban values 1 year later. For patients aged ≥ 65 years of age, immediate changes associated with the comprehensive ban were -5.0%, -3.9%, and -2.3% for AMI, IHD, and CVD, respectively (P<.05). Again, the 1-year changes were not statistically significant. CONCLUSIONS: In Spain, smoking bans failed to significantly reduce hospitalizations for AMI, IHD, or CVD among patients ≥ 18 years of age. In the population aged ≥ 65 years, hospital admissions due to these diseases showed significant decreases immediately after the implementation of the comprehensive ban, but these reductions disappeared at the 1-year evaluation.

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.

High adherence to the Western, Prudent, and Mediterranean dietary patterns and risk of gastric adenocarcinoma: MCC-Spain study.

BACKGROUND: The influence of dietary habits on the development of gastric adenocarcinoma is not clear. The objective of the present study was to explore the association of three previously identified dietary patterns with gastric adenocarcinoma by sex, age, cancer site, and morphology. METHODS: MCC-Spain is a multicase-control study that included 295 incident cases of gastric adenocarcinoma and 3040 controls. The association of the Western, Prudent, and Mediterranean dietary patterns-derived in another Spanish case-control study-with gastric adenocarcinoma was assessed using multivariable logistic regression models with random province-specific intercepts and considering a possible interaction with sex and age. Risk according to tumor site (cardia, non-cardia) and morphology (intestinal/diffuse) was evaluated using multinomial regression models. RESULTS: A high adherence to the Western pattern increased gastric adenocarcinoma risk [odds ratiofourth_vs._first_quartile (95% confidence interval), 2.09 (1.31; 3.33)] even at low levels [odds ratiosecond_vs._first_quartile (95% confidence interval), 1.63 (1.05; 2.52)]. High adherence to the Mediterranean dietary pattern could prevent gastric adenocarcinoma [odds ratiofourth_vs._first_quartile (95% confidence interval), 0.53 (0.34; 0.82)]. Although no significant heterogeneity of effects was observed, the harmful effect of the Western pattern was stronger among older participants and for non-cardia adenocarcinomas, whereas the protective effect of the Mediterranean pattern was only observed among younger participants and for non-cardia tumors. CONCLUSION: Decreasing the consumption of fatty and sugary products and of red and processed meat in favor of an increase in the intake of fruits, vegetables, legumes, olive oil, nuts, and fish might prevent gastric adenocarcinoma.

Meat intake, cooking methods and doneness and risk of colorectal tumours in the Spanish multicase-control study (MCC-Spain).

PURPOSE: Although there is convincing evidence that red and processed meat intake increases the risk of colorectal cancer (CRC), the potential role of meat cooking practices has not been established yet and could partly explain the current heterogeneity of results among studies. Therefore, we aimed to investigate the association between meat consumption and cooking practices and the risk of CRC in a population-based case-control study. METHODS: A total of 1671 CRC cases and 3095 controls recruited in Spain between September 2008 and December 2013 completing a food frequency questionnaire with a meat-specific module were included in the analyses. Odds ratios (OR) and confidence intervals (CI) were estimated by logistic regression models adjusted for known confounders. RESULTS: Total meat intake was associated with increased risk of CRC (OR T3-T1 1.41; 95% CI 1.19-1.67; p trend < 0.001), and similar associations were found for white, red and processed/cured/organ meat. Rare-cooked meat preference was associated with low risk of CRC in red meat (ORrare vs. medium 0.66; 95% CI 0.51-0.85) and total meat (ORrare vs. medium 0.56; 95% CI 0.37-0.86) consumers, these associations being stronger in women than in men. Griddle-grilled/barbecued meat was associated with an increased CRC risk (total meat: OR 1.45; 95% CI 1.13-1.87). Stewing (OR 1.25; 95% CI 1.04-1.51) and oven-baking (OR 1.18; 95% CI 1.00-1.40) were associated with increased CRC risk of white, but not red, meat. CONCLUSIONS: Our study supports an association of white, red, processed/cured/organ and total meat intake with an increased risk of CRC. Moreover, our study showed that cooking practices can modulate such risk.

Mediterranean Dietary Pattern is Associated with Low Risk of Aggressive Prostate Cancer: MCC-Spain Study.

PURPOSE: We explored the association of the previously described Western, prudent and Mediterranean dietary patterns with prostate cancer risk by tumor aggressiveness and extension. MATERIALS AND METHODS: MCC-Spain (Multicase-Control Study on Common Tumors in Spain) is a population based, multicase-control study that was done in 7 Spanish provinces between September 2008 and December 2013. It collected anthropometric, epidemiological and dietary information on 754 histologically confirmed incident cases of prostate cancer and 1,277 controls 38 to 85 years old. Three previously identified dietary patterns, including Western, prudent and Mediterranean, were reconstructed using MCC-Spain data. The association of each pattern with prostate cancer risk was assessed by logistic regression models with random, province specific intercepts. Risk according to tumor aggressiveness (Gleason score 6 vs greater than 6) and extension (cT1-cT2a vs cT2b-cT4) was evaluated by multinomial regression models. RESULTS: High adherence to a Mediterranean dietary pattern rich not only in fruits and vegetables but also in fish, legumes and olive oil was specifically associated with a lower risk of Gleason score greater than 6 prostate cancer (quartile 3 vs 1 relative RR 0.66, 95% CI 0.46-0.96 and quartile 4 vs 1 relative RR 0.68, 95% CI 0.46-1.01, p-trend = 0.023) or with higher clinical stage (cT2b-T4 quartile 4 vs 1 relative RR 0.49, 95% CI 0.25-0.96, p-trend = 0.024). This association was not observed with the prudent pattern, which combines vegetables and fruits with low fat dairy products, whole grains and juices. The Western pattern did not show any association with prostate cancer risk. CONCLUSIONS: Nutritional recommendations for prostate cancer prevention should consider whole dietary patterns instead of individual foods. We found important differences between the Mediterranean dietary pattern, which was associated with a lower risk of aggressive prostate cancer, and Western and prudent dietary patterns, which had no relationship with prostate cancer risk.

Industrial pollution and cancer in Spain: An important public health issue.

Cancer can be caused by exposure to air pollution released by industrial facilities. The European Pollutant Release and Transfer Register (E-PRTR) has made it possible to study exposure to industrial pollution. This study seeks to describe the industrial emissions in the vicinity of Spanish towns and their temporal changes, and review our experience studying industrial pollution and cancer. Data on industrial pollutant sources (2007-2010) were obtained from the E-PRTR registries. Population exposure was estimated by the distance from towns to industrial facilities. We calculated the amount of carcinogens emitted into the air in the proximity (<5km) of towns and show them in municipal maps. We summarized the most relevant results and conclusions reported by ecological E-PRTR-based on studies of cancer mortality and industrial pollution in Spain and the limitations and result interpretations of these types of studies. There are high amounts of carcinogen emissions in the proximity of towns in the southwest, east and north of the country and the total amount of emitted carcinogens is considerable (e.g. 20Mt of arsenic, 63Mt of chromium and 9Mt of cadmium). Although the emissions of some carcinogens in the proximity of certain towns were reduced during the study period, emissions of benzene, dioxins+furans and polychlorinated biphenyls rose. Moreover, the average population of towns lying within a 5km radius from emission sources of carcinogens included in the International Agency for Research on Cancer list of carcinogens was 9 million persons. On the other hand, the results of the reviewed studies suggest that those Spanish regions exposed to the pollution released by certain types of industrial facilities have around 17% cancer excess mortality when compared with those unexposed. Moreover, excess mortality is focused on digestive and respiratory tract cancers, leukemias, prostate, breast and ovarian cancers. Despite their limitations, ecological studies are a useful tool in environmental epidemiology, not only for proposing etiological hypotheses about the risk of living close to industrial pollutant sources, but also for providing data to account for situations of higher mortality in specific areas. Nevertheless, the reduction of emissions should be a goal, with special relevance given to establishing limits for known carcinogens and other toxic substances in the environs of population centers, as well as industry-specific emission limits.

Adherence to the Western, Prudent and Mediterranean dietary patterns and breast cancer risk: MCC-Spain study.

OBJECTIVE: To externally validate the previously identified effect on breast cancer risk of the Western, Prudent and Mediterranean dietary patterns. STUDY DESIGN: MCC-Spain is a multicase-control study that collected epidemiological information on 1181 incident cases of female breast cancer and 1682 healthy controls from 10 Spanish provinces. Three dietary patterns derived in another Spanish case-control study were analysed in the MCC-Spain study. These patterns were termed Western (high intakes of fatty and sugary products and red and processed meat), Prudent (high intakes of low-fat dairy products, vegetables, fruits, whole grains and juices) and Mediterranean (high intake of fish, vegetables, legumes, boiled potatoes, fruits, olives, and vegetable oil, and a low intake of juices). Their association with breast cancer was assessed using logistic regression models with random province-specific intercepts considering an interaction with menopausal status. Risk according to tumour subtypes - based on oestrogen (ER), progesterone (PR) and human epidermal growth factor 2 (HER2) receptors (ER+/PR+ & HER2-; HER2+; ER-/PR- & HER2-) - was evaluated with multinomial regression models. MAIN OUTCOME MEASURES: Breast cancer and histological subtype. RESULTS: Our results confirm most of the associations found in the previous case-control study. A high adherence to the Western dietary pattern seems to increase breast cancer risk in both premenopausal women (OR4thvs.1stquartile (95% CI):1.68 (1.02;2.79); OR1SD-increase (95% CI):1.19 (1.02;1.40)) and postmenopausal women (OR4thvs.1stquartile(95% CI):1.48(1.07;2.05); OR1SD-increase(95% CI): 1.14 (1.01;1.29)). While high adherence to the Prudent pattern did not show any effect on breast cancer, the Mediterranean dietary pattern seemed to be protective, but only among postmenopausal women (OR4thvs.1stquartile (95% CI): 0.72 (95% CI 0.53;0.98); p-int=0.075). There were no significant differences by tumour subtype. CONCLUSION: Dietary recommendations based on a departure from the Western dietary pattern in favour of the Mediterranean diet could reduce breast cancer risk in the general population.

Smoke-Free Legislation in Spain and Prematurity.

BACKGROUND AND OBJECTIVE: Spain implemented a partial smoking ban in 2006 followed by a comprehensive ban in 2011. The objective was to examine the association between these smoke-free policies and different perinatal complications. METHODS: Cross-sectional study including all live births between 2000 and 2013. Selected adverse birth outcomes were: preterm births (<37 gestational weeks), small for gestational age (SGA; <10th weight percentile according to Spanish reference tables), and low birth weight (<2500 g). We estimated immediate and gradual rate changes after smoking bans by using overdispersed Poisson models with different linear trends for 2000 to 2005 (preban), 2006 to 2010 (partial ban), and 2011 to 2013 (comprehensive ban). Models were adjusted for maternal sociodemographics, health care during the delivery, and smoking prevalence during pregnancy. RESULTS: The comprehensive ban was associated with preterm birth rate reductions of 4.5% (95% confidence interval [CI]: 2.9%-6.1%) and 4.1% (95% CI: 2.5%-5.6%) immediately and 1 year after implementation, respectively. The low birth weight rate also dropped immediately (2.3%; 95% CI: 0.7%-3.8%) and 1 year after the comprehensive ban implementation (3.5%; 95% CI: 2.1%-5.0%). There was an immediate reduction in the SGA rate at the onset of the partial ban (4.9%; 95% CI: 3.5%-6.2%), which was sustained 1 year postimplementation. Although not associated with the comprehensive ban at the onset, the SGA rate declined by 1.7% (95% CI: 0.3%-3.1%) 1 year postimplementation. CONCLUSIONS: The implementation of the Spanish smoke-free policies was associated with a risk reduction for preterm births and low birth weight infants, especially with the introduction of the more restrictive ban.

Helicobacter pylori Antibody Reactivities and Colorectal Cancer Risk in a Case-control Study in Spain.

Background: Several studies have suggested that Helicobacter pylori (H. pylori) infection is a risk factor for colorectal cancer (CRC), while others have not confirmed this hypothesis. This work aimed to assess the relation of CRC with H. pylori seropositivity and with seropositivity to 16 H. pylori proteins, in the MultiCase-Control study, MCC-Spain. Methods: MCC-Spain is a multicase-control study carried out in Spain from 2008 to 2013. In total, 2,140 histologically-confirmed incident CRC cases and 4,098 population-based controls were recruited. Controls were frequency-matched by sex, age, and province. Epidemiological data were collected through a questionnaire fulfilled by face-to-face interviews and a self-administered food-frequency questionnaire. Seroreactivities against 16 H. pylori proteins were determined in 1,488 cases and 2,495 controls using H. pylori multiplex serology. H. pylori seropositivity was defined as positivity to ≥4 proteins. Multivariable logistic regression mixed models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results:H. pylori seropositivity was not associated with increased CRC risk (OR = 0.91; 95% CI: 0.71-1.16). Among H. pylori seropositive subjects, seropositivity to Cagδ showed a lower CRC risk, and risk decreased with increasing number of proteins seropositive. Seropositivity to the most recognized virulence factors, CagA and VacA, was not associated with a higher CRC risk. No statistically significant heterogeneity was identified among tumor sites, although inverse relations were stronger for left colon cancer. An interaction with age and sex was found: H. pylori seropositivity was associated with a lower CRC risk in men younger than 65 and with a higher risk in older women. Conclusions: Our results suggest that neither H. pylori seropositivity, nor seropositivity to the virulence factor CagA are associated with a higher CRC risk. A possible effect modification by age and sex was identified.

Changes in hospitalizations for chronic respiratory diseases after two successive smoking bans in Spain.

BACKGROUND: Existing evidence on the effects of smoke-free policies on respiratory diseases is scarce and inconclusive. Spain enacted two consecutive smoke-free regulations: a partial ban in 2006 and a comprehensive ban in 2011. We estimated their impact on hospital admissions via emergency departments for chronic obstructive pulmonary disease (COPD) and asthma. METHODS: Data for COPD (ICD-9 490-492, 494-496) came from 2003-2012 hospital admission records from the fourteen largest provinces of Spain and from five provinces for asthma (ICD-9 493). We estimated changes in hospital admission rates within provinces using Poisson additive models adjusted for long-term linear trends and seasonality, day of the week, temperature, influenza, acute respiratory infections, and pollen counts (asthma models). We estimated immediate and gradual effects through segmented-linear models. The coefficients within each province were combined through random-effects multivariate meta-analytic models. RESULTS: The partial ban was associated with a strong significant pooled immediate decline in COPD-related admission rates (14.7%, 95%CI: 5.0, 23.4), sustained over time with a one-year decrease of 13.6% (95%CI: 2.9, 23.1). The association was consistent across age and sex groups but stronger in less economically developed Spanish provinces. Asthma-related admission rates decreased by 7.4% (95%CI: 0.2, 14.2) immediately after the comprehensive ban was implemented, although the one-year decrease was sustained only among men (9.9%, 95%CI: 3.9, 15.6). CONCLUSIONS: The partial ban was associated with an immediate and sustained strong decline in COPD-related admissions, especially in less economically developed provinces. The comprehensive ban was related to an immediate decrease in asthma, sustained for the medium-term only among men.

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.

Chemical quality of tap water in Madrid: multicase control cancer study in Spain (MCC-Spain).

Chronic consumption of water, which contains contaminants, may give rise to adverse health effects. The Madrid region, covered by the population-based multicase-control (MCC-Spain) study, includes two drinking water supply areas. The different sources of the water, coupled together with the possible differences in water management, mean that there may be differences in drinking water quality. In the context of the MCC study, our aims were to describe contaminant concentrations in tap water drawn from various sampling points distributed around the region, assess these concentrations by reference to guideline values and study possible differences between the two supply areas. Tap water samples were collected from 34 sampling points in 7 towns in the Madrid region (19-29 April 2010), and 23 contaminants (metals, nitrates, disinfection by-product and Mutagen X levels) were quantified. We undertook a descriptive analysis of the contaminant concentrations in the water and compared them between the two water supply areas (Wilcoxon test). We created maps representing the distribution of the concentrations observed at water sampling points and assessed the correlations (Spearman's coefficient) between the different parameters measured. The concentrations of the contaminants were below guideline values. There were differences between the two supply areas in concentration of nitrates (p value = 0.0051) and certain disinfection by-products. While there were positive correlations (rho >0.70) among some disinfection by-products, no correlations were found in metals or nitrates. The differences in nitrate levels could be linked to differences in farming/industrial activities in the catchment areas and in disinfection by-products might be related to the existence of different treatment systems or bromine content in source waters.

Ingested Nitrate and Breast Cancer in the Spanish Multicase-Control Study on Cancer (MCC-Spain).

BACKGROUND: Ingested nitrate leads to endogenous formation of N-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 ± SD waterborne ingested nitrate ranged from 2.9 ± 1.9 to 13.5 ± 7.5 mg/day, and dietary ingested nitrate ranged from 88.5 ± 48.7 to 154 ± 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. CITATION: Espejo-Herrera N, Gracia-Lavedan E, Pollan M, Aragonés N, Boldo E, Perez-Gomez B, Altzibar JM, Amiano P, Zabala AJ, Ardanaz E, Guevara M, Molina AJ, Barrio JP, Gómez-Acebo I, Tardón A, Peiró R, Chirlaque MD, Palau M, Muñoz M, Font-Ribera L, Castaño-Vinyals G, Kogevinas M, Villanueva CM. 2016. Ingested nitrate and breast cancer in the Spanish Multicase-Control Study on Cancer (MCC-Spain). Environ Health Perspect 124:1042-1049; http://dx.doi.org/10.1289/ehp.1510334.

Colorectal cancer risk and nitrate exposure through drinking water and diet.

Ingested nitrate leads to the endogenous synthesis of N-nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated with nitrate exposure in drinking water and diet. A case-control study in Spain and Italy during 2008-2013 was conducted. Hospital-based incident cases and population-based (Spain) or hospital-based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long-term waterborne ingested nitrate was derived from routine monitoring records, linked to subjects' residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors and other covariables. Generalized additive models (GAMs) were used to analyze exposure-response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. In total 1,869 cases and 3,530 controls were analyzed. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 versus ≤5 mg/day, overall. Associations were larger among men versus women, and among subjects with high red meat intake. GAMs showed increasing exposure-response relationship among men. Animal-derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research.

Perinatal and childhood factors and risk of breast cancer subtypes in adulthood.

BACKGROUND: Accumulated exposure to hormones and growth factors during early life may influence the future risk of breast cancer (BC). This study examines the influence of childhood-related, socio-demographic and anthropometric variables on BC risk, overall and by specific pathologic subtypes. METHODS: This is a case-control study where 1539 histologically-confirmed BC cases (23-85 years) and 1621 population controls, frequency matched by age, were recruited in 10 Spanish provinces. Perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with BC risk, globally and according to menopausal status and pathologic subtypes, was evaluated using logistic and multinomial regression models, adjusting for tumor specific risk factors. RESULTS: Birth characteristics were not related with BC risk. However, women with high socioeconomic level at birth presented a decreased BC risk (OR=0.45; 95% CI=0.29-0.70), while those whose mothers were aged over 39 years at their birth showed an almost significant excess risk of hormone receptor positive tumors (HR+) (OR=1.35; 95% CI=0.99-1.84). Women who were taller than their girl mates before puberty showed increased postmenopausal BC risk (OR=1.26; 95% CI=1.03-1.54) and increased HR+ BC risk (OR=1.26; 95% CI=1.04-1.52). Regarding prepubertal weight, while those women who were thinner than average showed higher postmenopausal BC risk (OR=1.46; 95% CI=1.20-1.78), associated with HR+ tumors (OR=1.34; 95% CI=1.12-1.61) and with triple negative tumors (OR=1.56; 95% CI=1.03-2.35), those who were heavier than average presented lower premenopausal BC risk (OR=0.64; 95% CI=0.46-0.90) and lower risk of epidermal growth factor receptor positive tumors (OR=0.61; 95% CI=0.40-0.93). CONCLUSION: These data reflect the importance of hormones and growth factors in the early stages of life, when the mammary gland is in development and therefore more vulnerable to proliferative stimuli.

Assessing the effects of the Spanish partial smoking ban on cardiovascular and respiratory diseases: methodological issues.

OBJECTIVE: Recent research has assessed the impact of tobacco laws on cardiovascular and respiratory morbidity. In this study, we also examined whether the association between the implementation of the 2005 Spanish smoking ban and hospital admissions for cardiovascular and respiratory diseases varies according to the adjustment for potential confounders. DESIGN: Ecological time series analysis. SETTING: Residents of Madrid and Barcelona cities (Spain). OUTCOME: Data on daily emergency room admissions for acute myocardial infarction, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), and asthma derived from the 2003-2006 Spanish hospital admissions registry. METHODS: Changes in admission rates between 2006 and the 2003-2005 period were estimated using additive Poisson models allowing for overdispersion adjusted for secular trend in admission, seasonality, day of the week, temperature, number of flu and acute respiratory infection cases, pollution levels, tobacco consumption prevalence and, for asthma cases, pollen count. RESULTS: In Madrid, fully adjusted models failed to detect significant changes in hospital admission rates for any disease during the study period. In Barcelona, however, hospital admissions decreased by 10.2% (95% CI 3.8% to 16.1%) for cerebrovascular diseases and by 16.0% (95% CI 7.0% to 24.1%) for COPD. Substantial changes in effect estimates were observed on adjustment for linear or quadratic trend. Effect estimates for asthma-related admissions varied substantially when adjusting for pollen count in Madrid, and for seasonality and tobacco consumption in Barcelona. CONCLUSIONS: Our results confirm that the potential impact of a smoking ban must be adjusted for the underlying secular trend. In asthma-related admissions, pollen count, seasonality and tobacco consumption must be specified in the model. The substantial variability in effects detected between the two cities of Madrid and Barcelona lends strong support for a nationwide study to assess the overall effect of a smoking ban in Spain and identify the causes of the observed heterogeneity.

Air quality modeling and mortality impact of fine particles reduction policies in Spain.

BACKGROUND: In recent years, Spain has implemented a number of air quality control measures that are expected to lead to a future reduction in fine particle concentrations and an ensuing positive impact on public health. OBJECTIVES: We aimed to assess the impact on mortality attributable to a reduction in fine particle levels in Spain in 2014 in relation to the estimated level for 2007. METHODS: To estimate exposure, we constructed fine particle distribution models for Spain for 2007 (reference scenario) and 2014 (projected scenario) with a spatial resolution of 16×16km(2). In a second step, we used the concentration-response functions proposed by cohort studies carried out in Europe (European Study of Cohorts for Air Pollution Effects and Rome longitudinal cohort) and North America (American Cancer Society cohort, Harvard Six Cities study and Canadian national cohort) to calculate the number of attributable annual deaths corresponding to all causes, all non-accidental causes, ischemic heart disease and lung cancer among persons aged over 25 years (2005-2007 mortality rate data). We examined the effect of the Spanish demographic shift in our analysis using 2007 and 2012 population figures. RESULTS: Our model suggested that there would be a mean overall reduction in fine particle levels of 1µg/m(3) by 2014. Taking into account 2007 population data, between 8 and 15 all-cause deaths per 100,000 population could be postponed annually by the expected reduction in fine particle levels. For specific subgroups, estimates varied from 10 to 30 deaths for all non-accidental causes, from 1 to 5 for lung cancer, and from 2 to 6 for ischemic heart disease. The expected burden of preventable mortality would be even higher in the future due to the Spanish population growth. Taking into account the population older than 30 years in 2012, the absolute mortality impact estimate would increase approximately by 18%. CONCLUSIONS: Effective implementation of air quality measures in Spain, in a scenario with a short-term projection, would amount to an appreciable decline in fine particle concentrations, and this, in turn, would lead to notable health-related benefits. Recent European cohort studies strengthen the evidence of an association between long-term exposure to fine particles and health effects, and could enhance the health impact quantification in Europe. Air quality models can contribute to improved assessment of air pollution health impact estimates, particularly in study areas without air pollution monitoring data.