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Objective: To evaluate the association between first-degree family history and colorectal cancer (CRC). Method: We analyzed data from 2857 controls and 1360 CRC cases, collected in the MCC-Spain project. The adjusted odds ratio (OR) and 95% confidence interval (95% CI) of association with the family history of CRC was estimated by non-conditional logistic regression. Result: First-degree relatives doubled the risk of CRC (OR: 2.19; 95% CI: 1.80-2.66), increasing in those with two or more (OR: 4.22; 95% CI: 2.29-7.78) and in those whose relatives were diagnosed before 50 years (OR: 3.24; 95% CI: 1.52-6.91). Regarding the association of the family history with the location, no significant differences were observed between colon and rectum, but there were in the relation of these with the age of diagnosis, having more relatives those diagnosed before 50 years (OR: 4.79; 95% CI: 2.65-8.65). Conclusions: First-degree relatives of CRC increase the chances of developing this tumor, they also increase when the relative is diagnosed at an early age. Therefore, it must be a target population on which to carry out prevention measures. (C) 2021 SESPAS. Published by Elsevier Espana, S.L.U.

La autora principal (garante responsable del manuscrito) afirma que este manuscrito es un reporte honesto, preciso y transparente del estudio que se remite a Gaceta Sanitaria, que no se han omitido aspectos importantes del estudio, y que las discrepancias del estudio según lo previsto (y, si son relevantes, registradas) se han explicado., A la Dra. Gemma Castaño Vinyals y al Dr. Manolis Kogevinas por su colaboración en el proyecto., Objetivo: El objetivo de este estudio es evaluar la asociación entre antecedentes familiares (AF) de primer grado y cáncer colorrectal (CCR). Método: Se incluyeron 2857 controles y 1360 casos de CCR, del estudio MCC-Spain. La odds ratio (OR) y el intervalo de confianza del 95% (IC95%) de los AF de primer grado y el CCR se estimaron mediante regresión logística no condicional según la localización tumoral en los casos. Resultados: Los AF de primer grado duplicaron el riesgo de CCR (OR: 2,19;IC95%: 1,80-2,66), incrementándose en aquellos que presentaban dos o más (OR: 4,22; IC95%: 2,29-7,78) y en aquellos cuyos familiares fueron diagnosticados antes de los 50 anos ˜ (OR: 3,24; IC95%: 1,52-6,91). Presentar AF se relacionó con estilos de vida como un menor consumo de vegetales. En cuanto a la asociación de los AF con la localización no se observaron diferencias significativas entre colon y recto, pero sí en la relación de estas con la edad de diagnóstico, presentando más AF los diagnosticados antes de los 50 anos ˜ (OR: 4,79; IC95%: 2,65-8,65). Conclusiones: Presentar AF de primer grado de CCR aumenta las probabilidades de desarrollar este cáncer, y también se elevan cuando el familiar es diagnosticado a edad temprana. Por ello, debe ser una población diana sobre la que incrementar las medidas de prevención., Objective: To evaluate the association between first-degree family history and colorectal cancer (CRC). Method: We analyzed data from 2857 controls and 1360 CRC cases, collected in the MCC-Spain project. The adjusted odds ratio (OR) and 95% confidence interval (95% CI) of association with the family history of CRC was estimated by non-conditional logistic regression. Results: First-degree relatives doubled the risk of CRC (OR: 2.19; 95% CI: 1.80–2.66), increasing in those with two or more (OR: 4.22; 95% CI: 2.29–7.78) and in those whose relatives were diagnosed before 50 years (OR: 3.24; 95% CI: 1.52–6.91). Regarding the association of the family history with the location, no significant differences were observed between colon and rectum, but there were in the relation of these with the age of diagnosis, having more relatives those diagnosed before 50 years (OR: 4.79; 95% CI: 2.65–8.65). Conclusions: First-degree relatives of CRC increase the chances of developing this tumor,they also increase when the relative is diagnosed at an early age. Therefore, it must be a target population on which to carry out prevention measures., El estudio fue parcialmente financiado por la «Acción Transversal del Cáncer», aprobada por el Consejo del Ministerio de España el 11 de octubre de 2007, por el 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), así como a través de CIBERESP CB06/02/0073, cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER). También cuenta con el apoyo de la Fundación Marqués de Valdecilla (API 10/09), el ICGC International Cancer Genome Consortium CLL (el proyecto ICGC CLL-Genome Project está financiado por el Ministerio de Economía y Competitividad española través del Instituto de Salud Carlos III y la Red Temática de Investigación del Cáncer del Instituto de Salud Carlos III [RD12 / 0036/0036]), la Junta de Castilla y León (LE22A10-2), la Consejería de Salud de la Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra), la Conselleria de Sanitat de la Generalitat Valenciana (AP 061/10), RecerCaixa (2010ACUP 00310), el Gobierno Regional del País Vasco, la Consejería de Sanidad de la Región de Murcia, la Comisión Europea de subvenciones FOOD-CT-2006-036224-HIWATE, la Fundación Científica de la Asociación Española Contra el Cáncer (AECC), la Generalitat de Catalunya - Agencia de Gestión Universitaria e Investigación Becas (AGAUR) y 2017SGR01085. Becas 2017SGR723 y 2014SGR850 de la Fundación Caja de Ahorros de Asturias y de la Universidad de Oviedo. ISGlobal agradece el apoyo del Ministerio de Ciencia e Innovación de España través del Programa Centro de Excelencia Severo Ochoa 2019-2023 (CEX2018-000806-S), y el apoyo de la Generalitat de Catalunya a través del Programa CERCA. M. Rubín-García cuenta con el apoyo del Ministerio de Educación de España (FPU17/06488).

Background: Gastric cancer is the fifth most frequent tumor worldwide. In Spain, it presents a large geographic variability in incidence, suggesting a possible role of environmental factors in its etiology. Therefore, epidemiologic research focused on environmental exposures is necessary. Objectives: To assess the association between risk of gastric cancer (by histological type and tumor site) and residential proximity to industrial installations, according to categories of industrial groups and specific pollutants released, in the context of a population-based multicase-control study of incident cancer conducted in Spain (MCC-Spain). Methods: In this study, 2664 controls and 137 gastric cancer cases from 9 provinces, frequency matched by province of residence, age, and sex were included. Distances from the individuals' residences to the 106 industries located in the study areas were computed. 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 industries, adjusting for matching variables and potential confounders. Results: Overall, no excess risk of gastric cancer was observed in people living close to the industrial installations, with ORs ranging from 0.73 (at ≤2.5 km) to 0.93 (at ≤1.5 km). However, by industrial sector, excess risks (OR; 95%CI) were found near organic chemical industry (3.51; 1.42-8.69 at ≤2 km), inorganic chemical industry (3.33; 1.12-9.85 at ≤2 km), food/beverage sector (2.48; 1.12-5.50 at ≤2 km), and surface treatment using organic solvents (3.59; 1.40-9.22 at ≤3 km). By specific pollutant, a statistically significant excess risk (OR; 95%CI) was found near (≤3 km) industries releasing nonylphenol (6.43; 2.30-17.97) and antimony (4.82; 1.94-12.01). Conclusions: The results suggest no association between risk of gastric cancer and living in the proximity to the industrial facilities as a whole. However, a few associations were detected near some industrial sectors and installations releasing specific pollutants. The authors thank all those who took part in this study by providing questionnaire data. This study was funded by: Scientific Foundation of the Spanish Association Against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC) e grants EVP-1178/14 and GCTRA18022MORE); “Acción Transversal del Cáncer”, approved on the Spanish Ministry Council on October 11, 2007; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP); Spain’s Health Research Fund (Fondo de Investigación Sanitaria - FIS 12/01416); Carlos III Institute of Health (ISCIII) grants, co-funded by ERDF fundsea way to build Europee (grants PI08/0533, PI08/1359, PI08/1770, PS09/00773, PS09/01286, PS09/01662, 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, PI14/01219, PI15/00069, PI15/00914, PI15/01032, PI17-00092, PI17CIII/00034); the Fundación Marqués de Valdecilla (API 10/09); the Junta de Castilla y León (LE22A10-2); the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra); the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10); the Recercaixa (2010ACUP 00310); the European Commission grants FOOD-CT-2006-036224-HIWATE; the Catalan Government-Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 and 2014SGR850; the Catalan Government DURSI grant 2014SGR647; the Fundación Caja de Ahorros de Asturias; and the University of Oviedo. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. No

Background: Some studies have reported an inverse association between type 2 diabetes mellitus (T2DM) and prostate cancer (PCa), but results on this issue are still inconsistent. In this study, we evaluate whether this heterogeneity might be related to differences in this relationship by tumour or by individual genetic susceptibility to PCa. Methods: We studied 1047 incident PCa cases and 1379 randomly selected controls, recruited in 7 Spanish provinces for the population-based MCC-Spain case-control. Tumour were classified by aggressiveness according to the International Society of Urological Pathology (ISUP), and we constructed a PCa polygenic risk score (PRS) as proxy for genetic susceptibility. The epidemiological questionnaire collected detailed self-reported data on T2DM diagnosis and treatment. The association between T2DM status and PCa was studied by fitting mixed logistic regression models, and, for its association by aggressiveness of PCa, with multinomial logistic regression models. To evaluate the possible modulator role of PRS in this relationship, we included the corresponding interaction term in the model, and repeated the analysis stratified by PRS tertiles. Results: Globally, our results showed an inverse association between T2DM and overall PCa limited to grade 1 tumours (ORISUP = 1: 0.72; 95% CI: 0.53-0.98), which could be compatible with a detection bias. However, PCa risk also varied with duration of diabetes treatment -inversely to metformin and positively with insulin-, without differences by aggressiveness. When we considered genetic susceptibility, T2DM was more strongly associated with lower PCa risk in those with lower PRS (ORtertile 1: 0.31; 95% CI: 0.11-0.87), independently of ISUP grade. Conclusions: Our findings reinforce the need to include aggressiveness and susceptibility of PCa, and T2DM treatments in the study of the relationship between both diseases.

The St Gallen Conference endorsed in 2013 a series of recommendations on early breast cancer treatment. The main purpose of this article is to ascertain the clinical factors associated with St Gallen-2013 recommendations accomplishment. A cohort of 1152 breast cancer cases diagnosed with pathological stage, Biological samples were stored at the biobanks supported by Instituto de Salud Carlos III-FEDER: Parc de Salut MAR Biobank (MARBiobanc) (RD09/0076/00036), ‘Biobanco La Fe’ (RD 09 0076/00021) and FISABIO Biobank (RD09 0076/00058), as well as at the Public Health Laboratory of Gipuzkoa, the Basque Biobank, the ICOBIOBANC (sponsored by the Catalan Institute of Oncology), the IUOPA Biobank of the University of Oviedo, and the ISCIII Biobank. SNP genotyping services were provided by the Spanish ‘Centro Nacional de Genotipado’ (CEGEN-ISCIII). We thank all the subjects who participated in the study and all MCC-Spain col laborators. 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, 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 (Grant 2014SGR647); the Fundación Caja de Ahorros de Asturias; the University of Oviedo; Societat Catalana de Diges tologia; and COST action BM1206 Eucolongene.

Background: Gastric cancer is the fifth most frequent tumor worldwide. In Spain, it presents a large geographic variability in incidence, suggesting a possible role of environmental factors in its etiology. Therefore, epidemiologic research focused on environmental exposures is necessary. Objectives: To assess the association between risk of gastric cancer (by histological type and tumor site) and residential proximity to industrial installations, according to categories of industrial groups and specific pollutants released, in the context of a population-based multicase-control study of incident cancer conducted in Spain (MCC-Spain). Methods: In this study, 2664 controls and 137 gastric cancer cases from 9 provinces, frequency matched by province of residence, age, and sex were included. Distances from the individuals' residences to the 106 industries located in the study areas were computed. 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 industries, adjusting for matching variables and potential confounders. Results: Overall, no excess risk of gastric cancer was observed in people living close to the industrial installations, with ORs ranging from 0.73 (at

Background: Self-reported data about environmental exposures can lead to measurement error. Objectives: To validate the self-reported perception of proximity to industrial facilities. Methods: MCC-Spain is a population-based multicase-control study of cancer in Spain that recruited incident cases of breast, colorectal, prostate, and stomach cancer. The participant’s current residence and the location of the industries were geocoded, and the linear distance between them was calculated (gold standard). The epidemiological questionnaire included a question to determine whether the participants perceived the presence of any industry at ≤1 km from their residences. Sensitivity and specificity of individuals' perception of proximity to industries were estimated as measures of classification accuracy, and the area under the curve (AUC) and adjusted odds ratios (aORs) of misclassification were calculated as measures of discrimination. Analyses were performed for all cases and controls, and by tumor location, educational level, sex, industrial sector, and length of residence. Finally, aORs of cancer associated with real and self-reported distances were calculated to explore differences in the estimation of risk between these measures. Results: Sensitivity of the questionnaire was limited (0.48) whereas specificity was excellent (0.89). AUC was sufficient (0.68). Participants with breast (aOR(95%CI)=2.03 (1.67;2.46)), colorectal (aOR(95%CI)=1.41 (1.20;1.64)) and stomach (aOR(95%CI)=1.59 (1.20;2.10)) cancer showed higher risk of misclassification than controls. This risk was higher for lower educational levels (aOR15 years (95%CI)=0.56 (0.36;0.85)). The use of selfreported proximity vs. real distance to industrial facilities biased the effect on cancer risk towards the nullity. Conclusions: Self-reported distance to industrial facilities can be a useful tool for hypothesis generation, but hypothesis-testing studies should use real distance to report valid conclusions. The sensitivity of the question might be improved with a more specific formulation, This study was funded by: Scientific Foundation of the Spanish Association Against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC) – EVP-1178/14), Spain's Health Research Fund (Fondo de Investigación Sanitaria – FIS 12/01416), the Spanish Ministry of Economy and Competitiveness (Carlos III Institute of Health; PI12/00488, PI12/00265, PI12/01270, PI12/ 00715, PI12/00150, 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, PI14/01219 and Río Hortega CM13/00232), the Catalan Government 2009SGR1489 & 2014SGR756-F, the Fundación Marqués de Valdecilla (API 10/09), the ICGC International Cancer Genome Consortium CLL, the Junta de Castilla y León (LE22A10-2), the Consejería de Salud of the Junta de Andalucía (PI-0571), the Conselleria de Sanitat of the Generalitat Valenciana (AP 061/10), the Recercaixa (2010ACUP 310), and the Regional Government of the Basque Country by European Commission grants FOOD-CT-2006-036224-HIWATE

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

Purpose To evaluate the association between dietary fat and fat subtype and breast cancer development. Methods We conducted a case-control study with 1181 cases of incident breast cancer, diagnosed between 2007 and 2012, and 1682 population controls frequency matched (by age, sex, and region) from the Spanish multicenter case-control study MCC-Spain. Results We found a significant protective effect in premenopausal women of total fat intake [OR 0.51 95% CI (0.31-0.86) highest versus lowest tertile], but no effect was observed in menopausal women [OR 1.15 95% CI (0.83-1.60)]. Analyzing by type of fat, this protective effect persisted only for the monounsaturated fatty acids [OR 0.51 95% CI (0.32-0.82)]. In contrast, other fatty acids did not have a significant effect. In addition, a protection against risk of breast cancer was found when polyunsaturated fats were "substituted" by monounsaturated, maintaining the same total fat intake [OR 0.68 95% CI (0.47-0.99)]. Finally, analyzing by breast cancer subtype, we found no effect, except in premenopausal women where intake of moderate [OR 0.52 95% CI (0.33-0.82)] and high monounsaturated fatty acids [OR 0.47 95% CI (0.27-0.82)] maintains a protective effect against ER/PR + tumors. In contrast, in menopausal women, a high intake of monounsaturated fatty acids was associated with higher risk of HER2 + tumors [OR 2.00 95% CI (0.97-4.13)]. Conclusion Our study shows a differential effect of monounsaturated fatty acids according to menopausal status and breast cancer subtype.

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

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

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

Instead of looking at individual nutrients or foods, dietary pattern analysis has emerged as a promising approach to examine the relationship between diet and health outcomes. Despite dietary patterns being compositional (i.e. usually a higher intake of some foods implies that less of other foods are being consumed), compositional data analysis has not yet been applied in this setting. We describe three compositional data analysis approaches (compositional principal component analysis, balances and principal balances) that enable the extraction of dietary patterns by using control subjects from the Spanish multicase-control (MCC-Spain) study. In particular, principal balances overcome the limitations of purely data-driven or investigator-driven methods and present dietary patterns as trade-offs between eating more of some foods and less of others., The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was partially funded by the ‘‘Accion Transversal del Cancer’’, approved by the Spanish Ministry Council on 11 October 2007; by the Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP); by the Instituto de Salud Carlos III-FEDER (grant nos PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PS09/01286-Leo´n, PS09/ 01903-Valencia, PS09/02078-Huelva, PS09/01662-Granada, PI11/01403, PI11/01810, PI11/02213, PI12/00488, PI14/01219, PI14/0613, PI15/00069, PI15/00914, PI15/01032, PI17/01280, PI09/0914, IJCI-2014-20900); by the Spanish Ministry of Health (grant no. CB06/02/1002); by the Spanish Ministry of Economy and Competitiveness (grant no. MTM2015-65016- C2-1-R); by the Catalan Government-Agency for Management of University and Research Grants (AGAUR) (grant nos 2014SGR551, 2017SGR656, 2017SGR733, 2017SGR723, 2017SGR1085); by the University of Girona (grant no. MPCUdG2016/069, GDRCompetUdG2017/19); by the Fundacio´n Marque´s de Valdecilla (grant no. API 10/09); by the Junta de Castilla y Leo´n (grant no. LE22A10-2); by the Consejerı´a de Salud of the Junta de Andalucı´a (grant nos PI-0571- 2009, PI-0306-2011, salud201200057018tra); by the Conselleria de Sanitat of the Generalitat Valenciana (grant no. AP_061/10); by the Regional Government of the Basque Country; by the Consejerı´a de Sanidad de la Regio´n de Murcia; by the European Commission (FOOD-CT-2006-036224-HIWATE); by the Spanish Association Against Cancer (AECC) Scientific Foundation; by the Fundacio´n Caja de Ahorros de Asturias; and by the University of Oviedo. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya.

Inflammation and antioxidant capacity have been associated with colorectal and breast cancer. We computed the dietary inflammatory index (DII&reg, ), and the total dietary non-enzymatic antioxidant capacity (NEAC) and associated them with colorectal and breast cancer risk in the population-based multi case-control study in Spain (MCC-Spain). We included 1852 colorectal cancer and 1567 breast cancer cases, and 3447 and 1486 population controls, respectively. DII score and NEAC were derived using data from a semi-quantitative validated food frequency questionnaire. Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI) for energy-adjusted DII (E-DII), and a score combining E-DII and NEAC. E-DII was associated with colorectal cancer risk (OR = 1.93, highest quartile versus lowest, 95%CI:1.60&ndash, 2.32, p-trend: &lt, 0.001), this increase was observed for both colon and rectal cancer. Less pronounced increased risks were observed for breast cancer (OR = 1.22, highest quartile versus lowest, 95%CI:0.99&ndash, 1.52, p-trend: &gt, 0.10). The combined score of high E-DII scores and low antioxidant values were associated with colorectal cancer risk (OR = 1.48, highest quartile versus lowest, 95%CI: 1.26&ndash, 1.74, 0.001), but not breast cancer. This study provides evidence that a pro-inflammatory diet is associated with increased colorectal cancer risk while findings for breast cancer were less consistent.

Purpose Since 2016, the multicase-control study in Spain (MCC-Spain) has focused towards the identification of factors associated with cancer prognosis. Inception cohorts of patients with colorectal, breast and prostate cancers were assembled using the incident cases originally recruited. Participants 2140 new cases of colorectal cancer, 1732 of breast cancer and 1112 of prostate cancer were initially recruited in 12 Spanish provinces; all cancers were incident and pathologically confirmed. Follow-up was obtained for 2097 (98%), 1685 (97%) and 1055 (94.9%) patients, respectively. Findings to date Information gathered at recruitment included sociodemographic factors, medical history, lifestyle and environmental exposures. Biological samples were obtained, and 80% of patients were genotyped using a commercial exome array. The follow-up was performed by (1) reviewing medical records; (2) interviewing the patients by phone on quality of life; and (3) verifying vital status and cause of death in the Spanish National Death Index. Ninety-seven per cent of recruited patients were successfully followed up in 2017 or 2018; patient-years of follow-up were 30 914. Most colorectal cancers (52%) were at clinical stage II or lower at recruitment; 819 patients died in the follow-up and the 5-year survival was better for women (74.4%) than men (70.0%). 71% of breast cancers were diagnosed at stages I or II; 206 women with breast cancer died in the follow-up and the 5-year survival was 90.7%. 49% of prostate cancers were diagnosed at stage II and 32% at stage III; 119 patients with prostate cancer died in the follow-up and the 5-year survival was 93.7%. Future plans MCC-Spain has built three prospective cohorts on highly frequent cancers across Spain, allowing to investigate socioeconomic, clinical, lifestyle, environmental and genetic variables as putative prognosis factors determining survival of patients of the three cancers and the inter-relationship of these factors, 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, PI18/00181), 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 (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

A breast-risk score, published in 2016, was developed in white-American women using 92 genetic variants (GRS92), modifiable and non-modifiable risk factors. With the aim of validating the score in the Spanish population, 1,732 breast cancer cases and 1,910 controls were studied. The GRS92, modifiable and non-modifiable risk factor scores were estimated via logistic regression. SNPs without available genotyping were simulated as in the aforementioned 2016 study. The full model score was obtained by combining GRS92, modifiable and non-modifiable risk factor scores. Score performances were tested via the area under the ROC curve (AUROC), net reclassification index (NRI) and integrated discrimination improvement (IDI). Compared with non-modifiable and modifiable factor scores, GRS92 had higher discrimination power (AUROC: 0.6195, 0.5885 and 0.5214, respectively). Adding the non-modifiable factor score to GRS92 improved patient classification by 23.6% (NRI = 0.236), while the modifiable factor score only improved it by 7.2%. The full model AUROC reached 0.6244. A simulation study showed the ability of the full model for identifying women at high risk for breast cancer. In conclusion, a model combining genetic and risk factors can be used for stratifying women by their breast cancer risk, which can be applied to individualizing genetic counseling and screening recommendations., The study was partially funded by the "Accion Transversal del Cancer" project, approved by the Spanish Council of Ministers on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PI09/00773-Cantabria, PI09/01286-Leon, 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), by the Fundacion Marques de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL (The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economia y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Tematica de Investigacion del Cancer (RTICC) del ISCIII (RD12/0036/0036)), by the Junta de Castilla y Leon (LE22A10-2), by the Consejeria de Salud of the Junta de Andalucia (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 European Commission grants FOOD-CT-2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation and by the Catalan Government DURSI grant 2009SGR1489.

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).

Tis 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, 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 Fundación Científca Asociación Española Contra el Cáncer (AECC); the Catalan Government DURSI (grant This work was supported by the 'Accion 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, and PI15/00069). Support was also provided by the Fundacion Marques de Valdecilla (grant API 10/09); the Junta de Castilla y Leon (grant LE22A10-2); the Consejeria de Salud of the Junta de Andalucia (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 Consejeria de Sanidad de la Region de Murcia; European Commission grants FOOD-CT-2006-036224-HIWATE; the Fundacion Cientifica Asociacion Espanola Contra el Cancer (AECC); the Catalan Government DURSI (grant 2014SGR647); the Fundacion Caja de Ahorros de Asturias; the University of Oviedo; Societat Catalana de Digestologia; and COST action BM1206 Eucolongene., Ibáñez-Sanz, G., Díez-Villanueva, A., Vilorio-Marqués, L., Gracia, E., Aragonés, N., Olmedo-Requena, R., Llorca, J., Vidán, J., Amiano, P., Nos, P., Fernández-Tardón, G., Rada, R., Chirlaque, M.D., Guinó, E., Dávila-Batista, V., Castaño-Vinyals, G., Pérez-Gómez, B., Mirón-Pozo, B., Dierssen-Sotos, T., Etxeberria, J., Molinuevo, A., Álvarez-Cuenllas, B., Kogevinas, M., Pollán, M., Moreno, V.

Background: In utero and early-life exposures are suspected to modulate the risk of prostate cancer. This study examines the influence of certain perinatal and childhood-related factors on prostate cancer risk overall and by Gleason score at biopsy. Methods: MCC-Spain is a multicase-control study where 1088 histologically-confirmed incident prostate cancer cases (aged 42-85 years) and 1345 population-based controls (aged 38-85 years), frequency matched by age and province of recruitment, were recruited in 7 Spanish provinces. Self-reported perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with prostate cancer risk, globally and according to Gleason score at biopsy, was evaluated using logistic and multinomial regression mixed models, adjusting for age, family history of prostate cancer, educational level and body mass index one year before the interview, and including the province as a random effect term. Results: Most perinatal factors were not related to prostate cancer risk, with the exception of middle-high socioeconomic level at birth (OR for high grade tumors = 1.36; 95%CI = 1.09-1.68). Regarding puberty, risk rose by 6% for each year of delayed onset (OR = 1.06; 95%CI = 1.01-1.10; p trend = 0.016), with a clear excess of risk in men who reached puberty after age 15 (OR: 1.35; 95%CI = 1.08-1.68). A borderline significant positive association with prepubertal height was also observed (p trend = 0.094). Conclusion: Some exposures experienced in utero and during adolescence, when the prostate is still maturing, might be relevant for prostate cancer risk in adulthood. (C) 2016 Elsevier Ltd. All rights reserved.