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Alkylphenolic compounds are chemicals with endocrine disrupting properties that have been widely used in industry with important changes in their usage over time. Few epidemiologic studies have evaluated the effect of alkylphenolic compounds on human health. We carried out a population-based case–control study including 1513 incident cases of breast cancer, 1095 of prostate cancer, and 3055 controls, frequency matched by sex, age and region. Occupational exposure to alkylphenolic compounds was estimated using a recently developed job-exposure matrix, which considered different scenarios of exposure and different subtypes of alkylphenolic compounds. Results: History of occupational exposure to alkylphenolic compounds was modestly associated with breast cancer (OR=1.23; 95% CI=1.01–1.48). Within the different scenarios, the occupational use of domestic tensioactives was positively associated with breast cancer (OR=1.28; 95% CI=1.02–1.60), while occupational exposure in other scenarios showed mostly a suggestion of a similar positive associations. Exposure to nonylphenol ethoxylates was positively associated with breast cancer (OR=1.21; 95% CI=1.00–1.47), while exposure to other compounds was uncommon. In general, we did not observe associations between alkylphenolic compounds and prostate cancer, except for a positive association among men occupationally exposed to cosmetic, hair and personal hygiene products. Our findings suggest a modest association between breast cancer risk and occupational exposure to alkylphenolic compounds, and no associations between these compounds and prostate cancer risk. These findings warrant further corroboration in other studies. ; This work was partially funded by the public grants from the Catalan Government (2014SGR756, 2017SGR1085, 2017SGR733, SLT006/17/76), and European Regional Development Fund-ERDF, by the "Accion Transversal del Cancer", approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos IIIFEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/ 01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/ 01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/ 00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/ 00914, PI15/01032, PI11/01810, PI14/01219, PI11/02213, PIE16/ 00049, PI17/01179), by the Fundación Marqués de Valdecilla (API 10/ 09), by the Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036), by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI- 0306-2011, salud201200057018tra), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government-Agency for Management of University and Research Grants (AGAUR) grants 2014SGR647 and 2014SGR850. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya.

We aimed to study the association between occupational exposure to pesticides and chronic lymphocytic leukemia (CLL) in Spain. Occupational exposure to pesticides (four insecticides, four herbicides and two fungicides) was evaluated using a job-exposure matrix for the Spanish population (MatEmESp) among 302 CLL cases and 1567 population controls in five regions of Spain, 2010–2013. Cumulative exposure scores (CES) were obtained by summing across the exposed jobs the product of prevalence, intensity and duration of exposure to each active substance. Principal components analysis (PCA) and logistic regression models adjusted for age, sex, region, education and occupational exposure to solvents were used. Around 20% of controls and 29% of cases were exposed to one or more pesticides. Compared to non-exposed, subjects in the highest tertile (3rd tertile) of CES of insecticides, herbicides, fungicides were more likely to have CLL [OR (95% CI), P-trend; 2.10 (1.38; 3.19), 0.002; 1.77 (1.12; 2.80), 0.12; and 1.67 (1.06; 2.64), 0.10, respectively). Following PCA, the first component (PC1, explaining 70% of the variation) equally led by seven active substances (the insecticide pyrethrin, all herbicides, all fungicides) was associated with a 26% higher odds of having CLL for 1-standard deviation increase in PC1 (95% CI: 1.14 to 1.40). These results confirm previous associations between CLL and exposure to pesticides and provide additional evidence by application groups and active substance. However, more research is needed to disentangle independent effects of individual active substances. ; Spanish Ministry of Economy and Competitiveness-Carlos III Institute of Health ; European Union (EU) PI08/1770 PI08/0533 PI08/1359 PS09/00773 PI11/01403 PI11/02213 PI14/1219 PI15/00966 PI17/01280 RTIC RD06/0020/0095 RD12/0036/0036 SV-09-CLINIC-1 ; Instituto de Salud Carlos III IJCI-2016-29502 ; Instituto de Salud Carlos III API 10/09 ; Obra Social CAJASTUR (SV-CAJASTUR-1) ; La Caixa Foundation 2010ACUP 00310 ; Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia 2017SGR1085 ; Spanish Ministerio de Economia y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) PMP15/00007 ; CIBERONC del ISCIII

Antibodies to Streptococcus gallolyticus subspecies gallolyticus (SGG) have been associated with colorectal cancer (CRC). Because SGG may correlate with impaired gut epithelia, we assessed the association of antibodies to bacterial flagellin C (FliC), a measure potentially related to this impairment, with CRC and the CRC-specific interaction with antibodies to SGG proteins. Antibodies to FliC and SGG pilus proteins Gallo2178 and Gallo2179 were measured in two independent studies, a combined study from Nijmegen and Detroit (93 CRC cases, 74 controls) and a replication data set including 576 cases and 576 controls from the Spanish multicenter multicase-control study (MCC-Spain). Logistic regression was applied to assess whether antibodies to FliC were associated with CRC and modified the association of antibodies to SGG proteins with CRC. Antibodies to FliC were associated with those to SGG Gallo2178 among CRC cases, resulting in an interaction in the association of antibodies to Gallo2178 with CRC (p = 0.007). This association was only present among individuals with high antibody responses to FliC (OR: 2.42, 95% CI: 1.45–4.06). In conclusion, our findings suggest that colorectal tumorigenesis could be accompanied by an impaired integrity of the epithelium that could result in associated increased antibody responses to bacterial proteins. ; This work was supported by the National Institutes of Health (grant number R01-CA93817, Ikuko Kato); The Netherlands Organization for Scientific Research (NWO 016.166.089 to A.B.); the "Acción Transversal del Cáncer", approved on the Spanish Ministry Council on the 11th October 2007; the Instituto de Salud Carlos III-FEDER funds –a way to build Europe- (grants numbers PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01662, PS09/01286, PS09/01903, PS09/02078, PI11/00226, PI11/01403, PI11/01810, PI11/01889, PI11/02213, PI12/00150, PI12/00265, PI12/00488, PI12/00715, PI12/01270, PI14/00613, PI17/00092); the Fundación Marques de Valdecilla (grant number API 10/09); Obra Social CAJASTUR (grant number SV-CAJASTUR-1); Recercaixa (grant number 2010ACUP 00310); Spanish Association Against Cancer (AECC) Scientific Foundation; Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) –Generalitat de Catalunya (Catalonian Government) (grant numbers 2009SGR1026, 2009SGR1465 and 2017SGR723); and Junta de Castilla y León (grant number LE022A10-2). Sample collection and storage was partially supported by the Instituto de Salud Carlos III-FEDER (grant number RD09/0076/00036), Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d'Oncologia de Catalunya (XBTC).

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]50.80, 95%CI 0.67–0.96) and in each cancer individually (prostate cancer OR50.74, 0.55–0.99; breast cancer OR50.84, 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 cancers5 0.65, 0.44–0.97) and in morning types (OR both cancers50.66, 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. ; Grant sponsor: Instituto de Salud Carlos III-FEDER; Grant number: PI11/01889; Grant sponsor: "Accion Transversal del Cancer," approved on the Spanish Ministry Council on the 11th October 2007; Grant sponsor: Instituto de Salud Carlos III-FEDER; Grant numbers: PI08/1770, PI08/0533, PI08/1359, PI09/00773-Cantabria, PI09/01286-León, PI09/01903-Valencia, PI09/02078-Huelva, PI09/01662-Granada, PI11/01889-FEDER, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI14/0613, PI15/00069, PI15/00914, PI15/01032; Grant sponsor: Regional Government of the Basque Country; Grant sponsor: Consejería de Sanidad de la Región de Murcia; Grant sponsor: European Commission grants FOOD-CT-2006–036224-HIWATE; Grant sponsor: Spanish Association Against Cancer (AECC) Scientific Foundation; Grant sponsor: Catalan Government DURSI grant; Grant number: 2014SGR647; Grant sponsor: Fundación Caja de Ahorros de Asturias and by the University of Oviedo

The aim was to assess the effect of adherence to the Mediterranean Diet, measured with five different indexes, on the risk of gastric cancer. Data come from the multicase-control study MCC—Spain, which included 354 gastric cancer cases and 3040 controls with data on diet. We used five indexes to evaluate adherence to the Mediterranean diet and assess the association between each pattern with the risk of gastric cancer, using multivariate logistic regression. The analyses were performed for the whole set of gastric cancer cases, by anatomical location (cardia and noncardia) and by histological type (intestinal and diffuse). According to the used index, a high adherence protects one from gastric cancer (between 48% (aOR = 0.52; CI 95% = 0.28–0.94) and 75% (aOR = 0.25; CI 95% = 0.12–0.52)), from non-cardia (between 48% (aOR = 0.52; CI 95% = 0.36–0.75) and 65% (aOR = 0.35; CI 95% = 0.23–0.52)), and from the intestinal type (between 41% (aOR = 0.59; CI 95% = 0.36–0.95) and 72% (aOR = 0.28; CI 95% = 0.16–0.50)), but not from the diffuse type. In conclusion, high adherence to a Mediterranean diet pattern is a protective factor for the risk of gastric cancer, with greater adherence leading to greater protection. ; Dietary habits are one of the factors that influence the development of gastric cancer and, although it has been seen that the Mediterranean diet has a protective effect on this type of cancer, there are different indexes to assess the degree of adherence to this dietary pattern; this implies differences in the results obtained in the reduction of risk. The aim of this work was to assess the effect of adherence to the Mediterranean diet, measured with five different indexes, on the risk of gastric cancer. ; The study was partially funded by the "Accion Transversal del Cancer", approved on the Spanish Ministry Council on 11 October 2007; by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078- Huelva, PS09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI17CIII/00034); by the Fundación Marqués de Valdecilla (API 10/09); by the ICGC International Cancer Genome Consortium CLL (the ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036)); by the Junta de Castilla y León (LE22A10-2); by the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra); by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10); by the Recercaixa (2010ACUP 00310); by the Regional Government of the Basque Country; by the Consejería de Sanidad de la Región de Murcia; by the European Commission grants FOOD-CT-2006-036224-HIWATE; by the Spanish Association Against Cancer (AECC) Scientific Foundation—grant GCTRA18022MORE; by the Catalan Government—Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 and 2014SGR850; by the Fundación Caja de Ahorros de Asturias; and by the University of Oviedo. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. M Obón-Santacana received a post-doctoral fellowship from the Spanish Association Against Cancer (AECC) Scientific Foundation. M Obón-Santacana is part of group 55 of CIBERESP and AGAUR 2017SGR723. M. R-G. is supported by the Ministry of Education of Spain (FPU17/06488).

This work was supported by FIS grants PI12/00150, PI17CIII/00034, PI18/00287 (Instituto de Salud Carlos III, State Secretary of R + D + I and European Union (ERDF/ESF, "Investing in your future") ) , P42ES010349 and P30ES009089 (National Institute of Environmental Health Sciences) . ; Toenails have been used as biomarkers of exposure to toxic metals, but their validity for this purpose is not yet clear and might differ depending on the specific agent. To evaluate this issue, we reviewed the literature on: a) the time-window of exposure reflected by toenails; b) the reproducibility of toenail toxic-metal levels in repeated measures over time; c) their relationship with other biomarkers of exposure, and; d) their association with potential determinants (i.e. sociodemographic, anthropometric, or lifestyle characteristics) or with sources of exposure like diet or environmental pollution. Thus, we performed a systematic review, searching for articles that provided original data for levels of any of the following toxic metals in toenails: aluminum, beryllium, cadmium, chromium, mercury, nickel, lead, thallium and uranium. We identified 88 articles, reporting data from 67 different research projects, which were quite heterogeneous with regard to population profile, sample size and analytical technique. The most commonly studied metal was mercury. Concerning the time-window of exposure explored by toenails, some reports indicate that toenail cadmium, nickel and lead may reflect exposures that occurred 7–12 months before sampling. For repeated samples obtained 1–6 years apart, the range of intraindividual correlation coefficients of aluminum, chromium and mercury was 0.33–0.56. The correlation of toxic metal concentrations between toenails and other matrices was higher for hair and fingernails than for urine or blood. Mercury levels were consistently associated with fish intake, while other toxic metals were occasionally associated with specific sources (e.g. drinking water, place of residence, environmental pollution, and occupation). The most frequently evaluated health endpoints were cardiovascular diseases, cancer, and central nervous system diseases. Available data suggest that toenail mercury levels reflected long-term exposures and showed positive associations with fish intake. The lack of standardization in sample collection, quality control, analytical techniques and procedures – along with the heterogeneity and conflicting results among studies – mean it is still difficult to conclude that toenails are a good biomarker of exposure to toxic metals. Further studies are needed to draw solid conclusions about the suitability of toenails as biomarkers of exposure to toxic metals. ; FIS (Instituto de Salud Carlos III, State Secretary of R + D + I) PI12/00150 PI17CIII/00034 PI18/00287 ; FIS (European Union (ERDF/ESF, "Investing in your future") PI12/00150 PI17CIII/00034 PI18/00287 U ; nited States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Environmental Health Sciences (NIEHS) P42ES010349 P30ES009089

A proportion of breast cancer cases are attributable to combined modifiable risk factors. The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) has recently updated the recommendations for cancer prevention and a standard scoring system has been published. The aim of this study was to evaluate the association between compliance with the 2018 WCRF/AICR cancer prevention recommendations (Third Expert Report) and the risk of breast cancer in the SUN ("Seguimiento Universidad de Navarra") prospective cohort. Spanish female university graduates, initially free of breast cancer, were included (n = 10,930). An 8-item score to measure compliance to the recommendations was built: body fat, physical activity, consumption of wholegrains/vegetables/fruit/beans, "fast foods", red/processed meat consumption, sugar-sweetened drinks consumption, alcohol intake, and breastfeeding. A stratified analysis was conducted according to menopausal status. A non-significant inverse association was observed for overall breast cancer. The inverse association became statistically significant for post-menopausal breast cancer after multivariable adjustment (hazard ratio for > 5 vs. ≤ 3 points = 0.27; 95% CI: 0.08-0.93). The results suggested that the possible inverse association with breast cancer was attributable to the combined effects of the different nutritional and lifestyle components. ; Instituto de Salud Carlos III PI10/02658 PI10/02293 PI13/00615 PI14/01668 PI14/01798 PI14/01764 PI17/01795 G03/140 ; European Union (EU) RD 06/0045 ; European Union (EU) PI10/02658 PI10/02293 PI13/00615 PI14/01668 PI14/01798 PI14/01764 PI17/01795 G03/140 ; Navarra Regional Government 45/2011 122/2014 41/2016 ; University of Navarra

Several anticancer properties have been largely attributed to phenolics in in vivo and in vitro studies, but epidemiologic evidence is still scarce. Furthermore, some classes have not been studied in relation to gastric cancer (GC). The aim of this study was to assess the relationship between the intake of phenolic acids, stilbenes, and other phenolics and the risk of developing GC and its anatomical and histological subtypes. We used data from a multi-case-control study (MCC-Spain) obtained from di erent regions of Spain. We included 2700 controls and 329 GC cases. Odds ratios (ORs) were calculated using mixed e ects logistic regression considering quartiles of phenolic intake. Our results showed an inverse association between stilbene and lignan intake and GC risk (ORQ4 vs. Q1 = 0.47; 95% CI: 0.32–0.69 and ORQ4 vs. Q1 = 0.53; 95% CI: 0.36–0.77, respectively). We found no overall association between total phenolic acid and other polyphenol class intake and GC risk. However, hydroxybenzaldehydes (ORQ4 vs. Q1 = 0.41; 95% CI: 0.28–0.61), hydroxycoumarins (ORQ4 vs. Q1 = 0.49; 95% CI: 0.34–0.71), and tyrosols (ORQ4 vs. Q1 = 0.56; 95% CI: 0.39–0.80) were inversely associated with GC risk. No di erences were found in the analysis by anatomical or histological subtypes. In conclusion, a diet high in stilbenes, lignans, hydroxybenzaldehydes, hydroxycoumarins, and tyrosols was associated with a lower GC risk. Further prospective studies are needed to confirm our results. ; Instituto de Salud Carlos III ; Instituto de Salud Carlos III European Union (EU) PI08/1770 PI08/0533 PI08/1359 PS09/00773-Cantabria PS09/01286-Leon PS09/01903-Valencia PS09/02078-Huelva PS09/01662-Granada PI11/01403 PI11/01889-FEDER PI11/00226 PI11/01810 PI11/02213 PI12/00488 ; Instituto de Salud Carlos III API 10/09 ; ICGC International Cancer Genome Consortium CLL (Spanish Ministerio de Economia y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII)) ; ICGC International Cancer Genome Consortium CLL (Spanish Ministerio de Economia y Competitividad (MINECO) through Red Tematica de Investigacion del Cancer (RTICC) del ISCIII) RD12/0036/0036 ; Junta de Castilla y León LE22A10-2 ; Junta de Andalucía PI-0571-200 PI-0306-2011 salud201200057018tra ; Conselleria de Sanitat of the Generalitat Valenciana AP_061/10 ; La Caixa Foundation 2010ACUP 00310 ; Regional Government of the Basque Country ; Consejería de Sanidad de la Región de Murcia ; European Commission European Commission Joint Research Centre FOOD-CT-2006-036224-HIWATE ; Spanish Association Against Cancer (AECC) Scientific Foundation ; Catalan Government Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 2014SGR850 ; Fundación Caja de Ahorros de Asturias ; University of Oviedo ; "Miguel Servet" program from the Institute of Health Carlos III (European Social Fund (ESF)-ESF investing in your future) CP15/00100 ; Ministry of Education of Spain FPU17/06488 ; University of Leon ; Spanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa 2019-2023" Program CEX2018-000806-S ; Generalitat de Catalunya through the CERCA Program ; The Instituto de Salud Carlos III-FEDER PI12/00265 PI12/01270 PI12/00715 PI12/00150 PI14/01219 PI14/0613 PI15/00069 PI15/00914 PI15/01032 PI17CIII/00034

Dyslipidemia and statin use have been associated with colorectal cancer (CRC), but prospective studies have shown mixed results. We aimed to determine whether dyslipidemia is causally linked to CRC risk using a Mendelian randomization approach and to explore the association of statins with CRC. A casecontrol study was performed including 1336 CRC cases and 2744 controls (MCC-Spain). Subjects were administered an epidemiological questionnaire and were genotyped with an array which included polymorphisms associated with blood lipids levels, selected to avoid pleiotropy. Four genetic lipid scores specific for triglycerides (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), or total cholesterol (TC) were created as the count of risk alleles. The genetic lipid scores were not associated with CRC. The ORs per 10 risk alleles, were for TG 0.91 (95%CI: 0.72–1.16, p = 0.44), for HDL 1.14 (95%CI: 0.95–1.37, p = 0.16), for LDL 0.97 (95%CI: 0.81–1.16, p = 0.73), and for TC 0.98 (95%CI: 0.84–1.17, p = 0.88). The LDL and TC genetic risk scores were associated with statin use, but not the HDL or TG. Statin use, overall, was a non-significant protective factor for CRC (OR 0.84; 95%CI: 0.70–1.01, p = 0.060), but lipophilic statins were associated with a CRC risk reduction (OR 0.78; 95%CI 0.66–0.96, p = 0.018). Using the Mendelian randomization approach, our study does not support the hypothesis that lipid levels are associated with the risk of CRC. This study does not rule out, however, a possible protective effect of statins in CRC by a mechanism unrelated to lipid levels. ; This work was supported by the 'Acción Transversal del Cancer', approved by the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III, co-founded by FEDER funds –'a way to build Europe' [grants PI08/1770, PI08/0533, PI08/1359, PI09/00773, PI09/01286, PI09/01903, PI09/02078, PI09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/00613, PI17/00092 and PI15/00069]. Support was also provided by the Fundación Marqués de Valdecilla (grant API 10/09]; the Junta de Castilla y León [grant LE22A10-2]; the Consejería de Salud of the Junta de Andalucía [2009-S0143]; the Conselleria de Sanitat of the Generalitat Valenciana [grant AP 061/10]; the Recercaixa [grant 2010ACUP 00310]; the Regional Government of the Basque Country; the Consejería de Sanidad de la Región de Murcia; European Commission grants FOOD-CT-2006-036224-HIWATE; the Spanish Association Against Cancer (AECC) Scientific Foundation; the Catalan Government DURSI [grants 2017SGR723 and 2014SGR850]; the Fundación Caja de Ahorros de Asturias; the University of Oviedo; Societat Catalana de Digestologia; and COST action CA17118 Transcoloncan.

Background: Night shift work, exposure to light at night (ALAN) and circadian disruption may increase the risk of hormone-dependent cancers. Objectives: We evaluated the association of exposure to ALAN during sleeping time with breast and prostate cancer in a population based multicase–control study (MCC-Spain), among subjects who had never worked at night. We evaluated chronotype, a characteristic that may relate to adaptation to light at night. Methods: We enrolled 1,219 breast cancer cases, 1,385 female controls, 623 prostate cancer cases, and 879 male controls from 11 Spanish regions in 2008–2013. Indoor ALAN information was obtained through questionnaires. Outdoor ALAN was analyzed using images from the International Space Station (ISS) available for Barcelona and Madrid for 2012–2013, including data of remotely sensed upward light intensity and blue light spectrum information for each geocoded longest residence of each MCC-Spain subject. Results: Among Barcelona and Madrid participants with information on both indoor and outdoor ALAN, exposure to outdoor ALAN in the blue light spectrum was associated with breast cancer [adjusted odds ratio (OR) for highest vs. lowest tertile, OR=1.47 ; 95% CI: 1.00, 2.17] and prostate cancer (OR=2.05; 95% CI: 1.38, 3.03). In contrast, those exposed to the highest versus lowest intensity of outdoor ALAN were more likely to be controls than cases, particularly for prostate cancer. Compared with those who reported sleeping in total darkness, men who slept in "quite illuminated" bedrooms had a higher risk of prostate cancer (OR=2.79; 95% CI: 1.55, 5.04), whereas women had a slightly lower risk of breast cancer (OR=0.77 ; 95% CI: 0.39, 1.51). Conclusion: Both prostate and breast cancer were associated with high estimated exposure to outdoor ALAN in the blue-enriched light spectrum. ; Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-León, PS09/01903-Valencia, PS09/02078-Huelva, PS09/01662-Granada, PI11/01889-FEDER, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI14/0613) ; Fundación Marqués de Valdecilla (API 10/09) ; Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036)], by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government–Agency for Management of University and Research Grants (AGAUR) grants 2014SGR647 and 2014SGR850, by the Fundación Caja de Ahorros de Asturias, and by the University of Oviedo. ISGlobal is a member of the Centres de Recerca de Catalunya (CERCA) Programme, Generalitat de Catalunya. ; This research was also supported in part by the STARS4ALL project funded by the H2020-ICT-2015-688135 program of the European Union, the ORISON project funded by the H2020-INFRASUPP-2015-2 program of the European Union, and through the resources of researchers and collaborators of the Cities at Night project. ; J.G.-P. was funded by the Scientific Foundation of the Spanish Association against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC), EVP-1178/14).

All author: Jéssica Alonso-Molero, Carmen González-Donquiles, Camilo Palazuelos, Tania Fernández-Villa, Elena Ramos, Marina Pollán, Nuria Aragonés, Javier Llorca, M. Henar Alonso, Adonina Tardón, Pilar Amiano, José Juan Jiménez Moleon, Rosana Peiró Pérez, Rocío Capelo, Antonio J. Molina, Inés Gómez Acebo, Marcela Guevara, Beatriz Perez-Gomez, Virginia Lope, José María Huerta, Gemma Castaño-Vinyals, Manolis Kogevinas, Victor Moreno and Vicente Martín. ; Background: The objective of our investigation is to study the relationship between the rs4939827 SNP in the SMAD7 gene, Mediterranean diet pattern and the risk of colorectal cancer. Methods: We examined 1087 cases of colorectal cancer and 2409 population controls with available DNA samples from the MCC-Spain study, 2008–2012. Descriptive statistical analyses, and multivariate logistic mixed models were performed. The potential synergistic effect of rs4939827 and the Mediterranean diet pattern was evaluated with logistic regression in different strata of of adherence to the Mediterranean diet and the genotype. Results: High adherence to Mediterrenean diet was statistically significantly associated with colorectal cancer risk. A decreased risk for CRC cancer was observed for the CC compared to the TT genotype (OR = 0.65 and 95% CI = 0.51–0. 81) of the rs4939827 SNP Also, we could show an association between the Mediterranean diet pattern (protective factor) and rs4939827. Although the decreased risk for the CC genotype was slightly more pronounced in subjects with high adherence to Mediterrenean diet, there was no statistically significant synergistic effect between genotype CC and adherence to the Mediterranean dietary pattern factors. Conclusion: The SMAD7 gene and specifically the allele C could be protective for colorectal cancer. An independent protective association was also observed between high adherence Mediterranean diet pattern and CRC risk. Findings form this study indicate that high adherence to Mediterranean diet pattern has a protective role for CRC cancer probably involving the Tumor Growth Factor- β pathway in this cancer. ; The study was partially funded by the "Accion Transversal del Cancer", approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PI09/00773-Cantabria, PI09/01286-León, PI09/01903-Valencia, PI09/02078-Huelva, PI09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTICC) del ISCIII (RD12/0036/0036)), by the Junta de Castilla y León (LE22A10–2), by the Consejería de Salud of the Junta de Andalucía (2009-S0143), by the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country, by the Consejería de Sanidad de la Región de Murcia, by the European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the Catalan Government DURSI grant 2014SGR647, by the Fundación Caja de Ahorros de Asturias and by the University of Oviedo.

Introduction: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Methods: Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. Discussion: This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain. ; The study was partially funded by the "Accion Transversal del Cancer", approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL, by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571), by the Conselleria de Sanitat of the Generalitat Valenciana (AP 061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country by European Commission grants FOOD-CT- 2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the The Catalan Government DURSI grant 2009SGR1489.

Sleep duration is a novel and potentially modifiable risk factor for cancer. We evaluated the association of self-reported sleep duration and daytime napping with odds of colorectal and gastric cancer. We included 2008 incident colorectal cancer cases, 542 gastric cancer cases and 3622 frequency-matched population controls, recruited in the MCC-Spain case–control study (2008–2013). Sleep information, socio-demographic and lifestyle characteristics were obtained through personal interviews. Multivariable adjusted logistic regression models were used to estimate odds ratios (OR) with 95% confidence intervals (CI) for cancer, across categories of sleep duration (≤ 5, 6, 7, 8, ≥ 9 hours/day), daytime napping frequency (naps/week) and duration (minutes/nap). Compared to 7 hours of sleep, long sleep was associated with increased odds of colorectal ( OR≥9 hours: 1.59; 95%CI 1.30–1.94) and gastric cancer ( OR≥9 hours: 1.95; 1.37–2.76); short sleep was associated with increased odds of gastric cancer ( OR≤5 hours: 1.32; 0.93–1.88). Frequent and long daytime naps increased the odds of colorectal ( OR6–7 naps/week, ≥30 min: 1.32; 1.14–1.54) and gastric cancer ( OR6–7 naps/week, ≥30 min: 1.56; 1.21–2.02). Effects of short sleep and frequent long naps were stronger among participants with night shift-work history. Sleep and circadian disruption may jointly play a role in the etiology of colorectal and gastric cancer. ; Catalan Government DURSI 2009SGR1489,RYC-2017-01892 ; Catalan Institute of Oncology ; Centro de Investigacion Biomedica en Red: Epidemiologia y Salud Publica ; Consejería de Salud of the Junta de Andalucía 2009-S0143 ; FEDER funds/European Regional Develpment Fund ; ICGC International Cancer Genome Consortium CLL ; ICOBIOBANC ; Red Temática de Investigación del Cáncer RD12/0036/0036 ; Spanish Association Against Cancer ; Xarxa de Bancs de Tumors de Cata-lunya ; Albert Einstein Cancer Center AECC ; Ministerio de Ciencia, Innovación y Universidades MCIU ; Eno Scientific Foundation ; European Commission FOOD-CT-2006-036224-HIWATE EC ; Generalitat de Catalunya 2017SGR723 ; Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR1085 AGAUR ; Ministerio de Economía y Competitividad MINECO ; Instituto de Salud Carlos III PI08/0533,PI08/1359,PI08/1770,PI11/00226,PI11/01403,PI11/01810,PI11/02213,PI12/00150,PI12/00265,PI12/00488,PI12/00715,PI12/01270 ISCIII ; Ministerio de Ciencia e Innovación CEX2018-000806-S MICINN ; European Social Fund ESF ; European Regional Development Fund PI17/01280 ERDF ; Conselleria de Sanitat Universal i Salut Pública 2010ACUP 00310,AP_061/10 ; Junta de Castilla y León LE22A10-2 ; Fundación Marqués de Valdecilla API 10/09 FMV

Background: Colorectal cancer is the third most frequent tumor in males and the second in females worldwide. In Spain, it is an important and growing health problem, and epidemiologic research focused on potential risk factors, such as environmental exposures, is necessary. Objectives: To analyze the association between colorectal cancer risk and residential proximity to industries, according to pollution discharge route, industrial groups, categories of carcinogens and other toxic substances, and specific pollutants released, in the context of a population-based multicase-control study of incident cancer carried out in Spain (MCC-Spain). Methods: MCC-Spain included 557 colorectal cancer cases and 2948 controls in 11 provinces, frequency matched by sex, age, and region of residence. Distances were computed from subjects' residences to each of the 134 industries located in the study area. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1 km to 3 km) to industrial facilities, adjusting for matching variables and other confounders. Results: Excess risk (OR; 95%CI) of colorectal cancer was detected near industries overall for all distances analyzed, from 1 km (2.03; 1.44–2.87) to 3 km (1.26; 1.00–1.59). In general, industries releasing pollutants to air showed higher excess risks than facilities releasing pollution to water. By industrial sector, excess risk (OR; 95%CI) was found near (≤3 km) production of metals (2.66; 1.77–4.00), surface treatment of metals (1.48; 1.08–2.02), glass and mineral fibers (2.06; 1.39–3.07), organic chemical industry (4.80; 3.20–7.20), inorganic chemical industry (6.74; 4.38–10.36), food/beverage sector (3.34; 2.38–4.68), and surface treatment using organic solvents (6.16; 4.06–9.36). By pollutants, the main excess risks (OR; 95%CI) were found near (≤3 km) industries releasing nonylphenol (9.19; 5.91–14.28), antimony (5.30; 3.45–8.15), naphthalene (3.11; 2.16–4.49), organotin compounds (2.64; 1.76–3.98), manganese (2.53; 1.63–3.93), dichloromethane (2.52; 1.74–3.66), and vanadium (2.49; 1.59–3.91). Conclusions: Our results support the hypothesis that residing in the proximity of industries may be a risk factor for colorectal cancer. ; Scientific Foundation of the Spanish Association Against Cancer (Fundacion Cientifica de la Asociacion Espanola Contra el Cancer (AECC)) EVP-1178/14 ; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) ; Instituto de Salud Carlos III FIS 12/01416 ; Carlos III Institute of Health (ISCIII) grants ; ERDF funds-a way to build Europe PI08/0533 PI08/1359 PI08/1770 PS09/00773Cantabria PS09/01286-Leon PS09/01662-Granada PS09/01903Valencia PS09/02078-Huelva PI11/00226 PI11/01403 PI11/01810 PI11/01889-FEDER PI11/02213 PI12/00150 PI12/00265 ; Fundacion Caja de Ahorros de Asturias ; University of Oviedo ; Junta de Castilla y Leon LE22A10-2 ; Regional Government of the Basque Country ; Conselleria de Sanitat of the Generalitat Valenciana AP_061/10 ; Junta de Andalucia PI-0571-2009 PI-0306-2011 salud201200057018tra ; Catalan Government DURSI grant 2014SGR647 ; European Commission European Commission Joint Research Centre FOOD-CT-2006036224-HIWATE ; La Caixa Foundation 2010ACUP 00310 ; Agency for Management of University and Research Grants (AGAUR) of the Catalan Government 2017SGR723 ; Spanish Association Against Cancer (AECC) Scientific Foundation ; The ERDF funds-a way to build Europe PI12/00488 PI12/00715 PI12/01270 PI14/00613 PI14/01219 PI15/00069 PI15/00914 PI15/01032 PI17-00092