Helicobacter pylori seroprevalence in Spain: influence of adult and childhood sociodemographic factors.

Helicobacter pylori (H. pylori) chronic infection causes severe digestive diseases, including gastric cancer, and certain strains entail a higher risk. Risk factors for this infection are still not fully understood. The aim of this study was to describe the association of adult and childhood sociodemographic factors with the seroprevalence of H. pylori, and with CagA and VacA antigen-specific seropositivity among H. pylori-seropositive individuals in the Spanish adult population. Serum antibody reactivity to H. pylori proteins was evaluated using multiplex serology in 2555 population-based controls enrolled in the MCC-Spain study, a multicase-control study recruiting participants from 2008 to 2013 in different areas of Spain. H. pylori seroprevalence was defined as seropositivity against at least four bacterial proteins. Information on sociodemographics, lifestyles, and environmental exposures was collected through personal interviews. Prevalence ratios and 95% confidence intervals were estimated using Poisson regression models to assess the association of lifetime sociodemographic factors with H. pylori seroprevalence and with seropositivity for CagA and VacA. H. pylori seroprevalence was 87.2%. Seropositivity was statistically significantly higher in men, increased with age, BMI, and number of siblings, and decreased with education and socioeconomic family level at birth. Among H. pylori-seropositive individuals, seropositivity was 53.3% for CagA, 61.4% for VacA, and 38.8% for both CagA and VacA. Ever smokers had lower seroprevalence for CagA and VacA than never smokers. H. pylori seroprevalence among this Spanish adult population was high and one third of the population was seropositive for two well-known markers of gastric cancer risk: CagA and VacA. Sex, age, education, and BMI were associated with H. pylori seroprevalence.

Epidemiology of non-steroidal anti-inflammatory drugs consumption in Spain. The MCC-Spain study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used despite their risk of gastrointestinal bleeding or cardiovascular events. We report the profile of people taking NSAIDs in Spain, and we include demographic factors, health-related behaviours and cardiovascular disease history. METHODS: Four thousand sixtyparticipants were selected using a pseudorandom number list from Family Practice lists in 12 Spanish provinces. They completed a face-to-face computerized interview on their NSAID consumption, demographic characteristics, body mass index, alcohol and tobacco consumption and medical history. In addition, participants completed a self-administered food-frequency and alcohol consumption questionnaire. Factors associated with ever and current NSAID consumption were identified by logistic regression. RESULTS: Women consumed more non-aspirin NSAIDs (38.8% [36.7-41.0]) than men (22.3 [20.5-24.2]), but men consumed more aspirin (11.7% [10.3-13.2]) than women (5.2% [4.3-6.3]). Consumption of non-aspirin NSAIDs decrease with age from 44.2% (39.4-49.1) in younger than 45 to 21.1% (18.3-24.2) in older than 75, but the age-pattern for aspirin usage was the opposite. Aspirin was reported by about 11% patients, as being twice as used in men (11.7%) than in women (5.2%); its consumption increased with age from 1.7% (< 45 years old) to 12.4% (≥75 years old). Aspirin was strongly associated with the presence of cardiovascular risk factors or established cardiovascular disease, reaching odds ratios of 15.2 (7.4-31.2) in women with acute coronary syndrome, 13.3 (6.2-28.3) in women with strokes and 11.1 (7.8-15.9) in men with acute coronary syndrome. Participants with cardiovascular risk factors or diseases consumed as much non-aspirin NSAID as participants without such conditions. CONCLUSIONS: Non-aspirin NSAIDs were more consumed by women and aspirin by men. The age patterns of aspirin and non-aspirin NSAIDs were opposite: the higher the age, the lower the non-aspirin NSAIDs usage and the higher the aspirin consumption. People with cardiovascular risk factors or diseases consumed more aspirin, but they did not decrease their non-aspirin NSAIDs usage.

Effect of mistimed eating patterns on breast and prostate cancer risk (MCC-Spain Study).

Modern life involves mistimed sleeping and eating patterns that in experimental studies are associated with adverse health effects. We assessed whether timing of meals is associated with breast and prostate cancer risk taking into account lifestyle and chronotype, a characteristic correlating with preference for morning or evening activity. We conducted a population-based case-control study in Spain, 2008-2013. In this analysis we included 621 cases of prostate and 1,205 of breast cancer and 872 male and 1,321 female population controls who had never worked night shift. Subjects were interviewed on timing of meals, sleep and chronotype and completed a Food Frequency Questionaire. Adherence to the World Cancer Research Fund/American Institute of Cancer Research recommendations for cancer prevention was examined. Compared with subjects sleeping immediately after supper, those sleeping two or more hours after supper had a 20% reduction in cancer risk for breast and prostate cancer combined (adjusted Odds Ratio [OR] = 0.80, 95%CI 0.67-0.96) and in each cancer individually (prostate cancer OR = 0.74, 0.55-0.99; breast cancer OR = 0.84, 0.67-1.06). A similar protection was observed in subjects having supper before 9 pm compared with supper after 10 pm. The effect of longer supper-sleep interval was more pronounced among subjects adhering to cancer prevention recommendations (OR both cancers= 0.65, 0.44-0.97) and in morning types (OR both cancers = 0.66, 0.49-0.90). Adherence to diurnal eating patterns and specifically a long interval between last meal and sleep are associated with a lower cancer risk, stressing the importance of evaluating timing in studies on diet and cancer.

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.

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.

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.

Helicobacter pylori serological biomarkers of gastric cancer risk in the MCC-Spain case-control Study.

BACKGROUND: Helicobacter pylori infection is one of the main risk factors for non-cardia gastric cancer. However, only a minority of infected persons develop the disease. This study aims at identifying H. pylori related serological biomarkers of risk for gastric cancer. METHODS: Incident gastric cancer cases and population controls (age, sex and region frequency-matched) from the MCC-Spain multicase-control Study were included. Seroreactivities against 16H. pylori proteins were determined using multiplex serology. Infection was defined as seropositivity against≥4 proteins. Relation of serological results to non-cardia and cardia gastric cancer was assessed using multivariable mixed logistic regression and principal components analysis. RESULTS: Seroprevalence was 88% among 2071 controls, 95% among 202 non-cardia gastric cancer cases (OR=1.9 (95% CI: 1.0-3.6)) and 85% among 62 cardia cancer cases (OR=0.5 (95% CI: 0.3-1.1)). In infected subjects, seropositivity for UreA, HP231, NapA and Cagδ was associated with lower non-cardia gastric cancer risk, while seropositivity for CagA and VacA was associated with higher risk. Seropositivity for CagA and seronegativity for Cagδ maintained the association after additional adjustment by serostatus of significant proteins. We identified two antibody reactivity patterns: the "virulent-pattern", related to a threefold higher risk of non-cardia gastric cancer and the "non-virulent pattern", related to a 60% decreased risk (4th vs. first quartile). CONCLUSIONS: In our population, people seropositive for H. pylori were characterized by two patterns of antibody reactivity against H. pylori proteins: 1) Combined high seroreactivity against several proteins, associated with a lower non-cardia gastric cancer risk, and 2) High seroreactivity against CagA and VacA, associated with an increased risk.

Physical activity domains and risk of gastric adenocarcinoma in the MCC-Spain case-control study.

BACKGROUND: Evidence for a protective role of physical activity against development of stomach cancer is yet inconclusive. We studied the association of domain-specific physical activity and the risk of gastric adenocarcinoma (GAC), by site and histology, in the MCC-Spain case-control study. METHODS: 428 histologically confirmed GAC cases (67% men) including the gastro-esophageal region and 3225 controls were included. Cases were recruited in hospitals from 10 different Spanish regions, whereas population controls were randomly selected within the respective hospitals' catchment areas. A physical activity (PA) questionnaire was used to gather information on household and recreational activities, allowing estimation of PA volume (in metabolic equivalents (MET)-min/week). Participants also reported the intensity of working PA and daily sitting time. Questionnaire data on diet, lifestyles and clinical variables including Helicobacter pylori serology were available. Adjusted odds ratios (OR) of GAC were estimated for domains of physical activity, stratifying by sex, site (cardia vs. non-cardia), and Lauren classification (intestinal vs. diffuse). RESULTS: Household physical activity (HPA) showed a strong inverse association with GAC, observed for both cardia and non-cardia tumours. Risk of overall gastric cancer was 50% lower risk among participants in the highest HPA category (OR = 0.50, 95%CI: 0.38, 0.66). Recreational physical activity (RPA) was also associated with lower overall GAC risk (OR = 0.68, 95% CI: 0.52, 0.88), particularly at moderate levels of intensity such as walking (OR = 0.61, 95% CI: 0.46, 0.79). The protective effect of RPA was strongest for non-cardia tumours. Sedentary time was not related to GAC risk (p-trend = 0.392), but the potential protective effect of RPA was restricted to non-sedentary participants. CONCLUSIONS: Both household and recreational physical activities were independently related to lower GAC risk in the MCC-Spain study.

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.

Shift work and colorectal cancer risk in the MCC-Spain case-control study.

Objectives Shift work that involves circadian disruption has been associated with a higher cancer risk. Most epidemiological studies to date have focused on breast cancer risk and evidence for other common tumors is limited. We evaluated the risk for colorectal cancer (CRC) in relation to shift work history in a population-based case-control study in Spain. Methods This analysis included 1626 incident CRC cases and 3378 randomly selected population controls of both sexes, enrolled in 11 regions of Spain. Sociodemographic and lifestyle information was assessed in face-to-face interviews. Shift work was assessed in detail throughout lifetime occupational history. We estimated the risk of colon and rectal cancer associated with rotating and permanent shift work (ever, cumulative duration, age of first exposure) using unconditional logistic regression analysis adjusting for potential confounders. Results Having ever performed rotating shift work (morning, evening and/or night) was associated with an increased risk for CRC [odds ratio (OR) 1.22, 95% confidence interval (95% CI) 1.04-1.43], as compared to day workers. Having ever worked permanent night shifts (≥3 nights/month) was not associated with CRC risk (OR 0.79, 95% CI 0.62-1.00). OR increased with increasing lifetime cumulative duration of rotating shift work (P-value for trend 0.005) and were highest among subjects in the top quartiles of exposure (3 rdquartile, 20-34 years, OR 1.38, 95%CI 1.06-1.81; 4 thquartile, ≥35 years, OR 1.36, 95% CI 1.02-1.79). Conclusions These data suggest that rotating shift work may increase the risk of CRC especially after long-term exposures.

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.

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.

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.

[How to assess and reduce social inequalities in cancer screening programmes]. / Cómo evaluar y reducir desigualdades sociales en los programas de cribado de cáncer.

This field note presents the conclusions and recommendations made at the meeting 'How to reduce social inequalities in cancer screening programmes?' held at the XXVI School of Public Health of Mahon (Menorca, Spain). Participants developed recommendations based on experiences of population-based screening programmes (breast and colorectal) and opportunistic screening (cervical). The conclusions and recommendations focused on four main areas (information systems, evaluation and quality, research, and interventions): the inclusion of social variables at an individual level in health information systems; the establishment of minimum standards for gathering information regarding inequalities in access to preventive services; the performance of actions in vulnerable populations; and the promotion of the exchange of experiences and best practices through the Cancer Screening Programmes Network and working groups of the scientific societies.