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Objectives: Adherence to healthy lifestyle recommendations has been reported to improve health-related quality of life (HRQL) in breast cancer (BC) patients, but the influence of long-term behavioral changes remains unknown. We evaluated the association between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and HRQL both, at BC diagnosis and the change 7−12 years later. Design: Prospective cohort study. Settings and participants: A total of 406 breast cancer survivors, from the EpiGEICAM study, were recruited in 16 Spanish hospitals. Measurements: Epidemiological, clinical, dietary, physical activity and HRQL information was collected both at recruitment and 7−12 years later. A 7-item score to measure compliance with recommendations was assessed according to the 2018 WCRF/AICR scoring criteria. HRQL was evaluated using SF-36 questionnaire. Linear mixed models for longitudinal data were used to assess the cross-sectional and longitudinal association between adherence score and the physical and mental component summary scores. Results: At diagnosis, for each unit increase in WCRF/AICR score adherence, the HRQL physical domain increased 0.78 points (95%CI: −0.04 to 1.60; P trend:0.06). The mean change in physical HRQL from diagnosis to follow-up per unit increase in within-subject adherence score was 0.73 points (95%CI: −0.18 to 1.65; P trend: 0.12). For the mental domain, no association was observed with compliance with the recommendations at diagnosis, nor with changes in adherence over time. Conclusions: Our results suggest that Increased adherence to WCRF/AICR cancer prevention recommendations over time could contribute to slightly improved long-term physical HRQoL in BC survivors.

The aim of our study is to evaluate the relationship between sociodemographic and clinical characteristics of individuals with Colorectal Cancer (CRC), tumour-intrinsic characteristics and treatment received with health-related quality of life (HRQoL). Methods: Cross-sectional analysis of data from 805 survivors from the MCC study was conducted. HRQoL was assessed through a general and specific questionnaire, SF-12 and FCSI (Colorectal Symptom Index). Statistical analyses were performed with linear regression with adjustment for sociodemographic variables, stage at diagnosis and histological grade. Results: Participants had survived a median of 7.9 years from diagnosis (IQR 7.1–8.5 years). Age at diagnosis, sex and area showed a clear association with HRQoL in both physical and mental dimensions of the SF-12 questionnaire. A direct association between CRC recurrence was also found in the PCS-12 and MCS-12 dimensions and radical surgery in the PCS-12. Regarding the scores in FCSI questionnaire, statistically significant differences were observed by sex, age and area, with older women being the most impaired (p < 0.001). Conclusions: Age, sex and area was associated with lower scores of HRQoL among CRC survivors. Knowing the determinants related to HRQoL would allow us to lay the groundwork to develop strategies that help reduce morbidity and mortality, relapses and increase HRQoL.

Abstract Purpose To build models combining circulating microRNAs (miRNAs) able to identify women with breast cancer as well as different types of breast cancer, when comparing with controls without breast cancer. Method miRNAs analysis was performed in two phases: screening phase, with a total n = 40 (10 controls and 30 BC cases) analyzed by Next Generation Sequencing, and validation phase, which included 131 controls and 269 cases. For this second phase, the miRNAs were selected combining the screening phase results and a revision of the literature. They were quantified using RT-PCR. Models were built using logistic regression with LASSO penalization. Results The model for all cases included seven miRNAs (miR-423-3p, miR-139-5p, miR-324-5p, miR-1299, miR-101-3p, miR-186-5p and miR-29a-3p); which had an area under the ROC curve of 0.73. The model for cases diagnosed via screening only took in one miRNA (miR-101-3p); the area under the ROC curve was 0.63. The model for disease-free cases in the follow-up had five miRNAs (miR-101-3p, miR-186-5p, miR-423-3p, miR-142-3p and miR-1299) and the area under the ROC curve was 0.73. Finally, the model for cases with active disease in the follow-up contained six miRNAs (miR-101-3p, miR-423-3p, miR-139-5p, miR-1307-3p, miR-331-3p and miR-21-3p) and its area under the ROC curve was 0.82. Conclusion We present four models involving eleven miRNAs to differentiate healthy controls from different types of BC cases. Our models scarcely overlap with those previously reported.

Introduction The role of cigarette smoking on breast cancer risk remains controversial, due to its dual carcinogenic-antiestrogenic action. Methods In the population-based multi-case-control study (MCC-Spain), we collected epidemiological and clinical information for 1733 breast cancer cases and 1903 controls, including smoking exposure. The association with breast cancer, overall, by pathological subtype and menopausal status, was assessed using logistic and multinomial regression models. Results Smokers had higher risk of premenopausal breast cancer, particularly if they had smoked ≥30 years (AOR=1.75; 95% CI: 1.04–2.94), although most estimates did not achieve statistical significance. In contrast, among postmenopausal women, smoking was associated with lower risk of breast cancer, mainly in overweight and obese women. The strongest risk reductions were observed among postmenopausal women who had stopped smoking ≥10 years before cancer diagnosis, particularly for HER2+ tumors (AOR=0.28; 95% CI: 0.11–0.68); p for heterogeneity = 0.040). Also, those who had smoked

Background: In 2021, the Spanish Ministry of Health launched the CIBERPOSTCOVID project to establish what post COVID was. The present study reports the level of agreement among stakeholders on post COVID and its clinical and diagnostic characteristics in the Spanish health system. Methods: The agreement on post COVID among clinicians, public health managers, researchers and patients’ representatives was explored in a real-time, asynchronous online Delphi. In a two-wave consensus, respondents rated from 1 (total disagreement) to 6 (total agreement) 67 statements related to terminology, duration, etiology, symptoms, impact on quality of life, severity, elements to facilitate diagnosis, applicability in the pediatric population, and risk factors. Consensus was reached when 70 % of ratings for a statement were 5 or 6, with an interquartile range equal or less than 1. Findings: A total of 333 professionals and patients participated in this eDelphi study. There was agreement that post COVID was “a set of multi-organic symptoms that persist or fluctuate after acute COVID-19 infection and are not attributable to other causes” with a minimum duration of 3 months. The highest levels of agreement were found in the most frequent symptoms and its impacts on everyday activities. Aspects related to the diagnostic process and the measurement of its severity reached a lower level of consensus. There was agreement on the need to rule out previous health problems and assess severity using validated functional scales. However, no agreement was reached on the risk factors or specific features in the pediatric population. Interpretation: This policy-based consensus study has allowed the characterization of post COVID generating collective intelligence and has contributed to an operational definition applicable in clinical practice, health services management and useful for research purposes in Spain and abroad. Agreements are consistent with existing evidence and reference institutions at European and international level.

Abstract We assessed the impact of the first wave of COVID-19 pandemic on non-COVID hospital admissions, non-COVID mortality, factors associated with non-COVID mortality, and changes in the profile of non-COVID patients admitted to hospital. We used the Spanish Minimum Basic Data Set with diagnosis grouped according to the Diagnostic Related Groups. A total of 10,594 patients (3% COVID-19; 97% non-COVID) hospitalised during the first wave in 2020 (27-February/07-June) were compared with those hospitalised within the same dates of 2017–2019 (average annual admissions: 14,037). We found a decrease in non-COVID medical (22%) and surgical (33%) hospitalisations and a 25.7% increase in hospital mortality among non-COVID patients during the first pandemic wave compared to pre-pandemic years. During the officially declared sub-period of excess mortality in the area (17-March/20-April, in-hospital non-COVID mortality was even higher (58.7% higher than the pre-pandemic years). Non-COVID patients hospitalised during the first pandemic wave (compared to pre-pandemic years) were older, more frequently men, with longer hospital stay and increased disease severity. Hospitalisation during the first pandemic wave in 2020, compared to hospitalisation during the pre-pandemic years, was an independent risk factor for non-COVID mortality (HR 1.30, 95% CI 1.07–1.57, p = 0.008), reflecting the negative impact of the pandemic on hospitalised patients.

Abstract Breast and prostate cancers have been associated with circadian disruption. Some previous studies examined associations of sleep duration and breast or prostate cancer risk though findings remain inconsistent. This study examines associations of a range of detailed sleep characteristics and breast and prostate cancer risk in a large-scale population-based case–control study, MCC-Spain. A total of 1738 incident breast cancer cases, 1112 prostate cancer cases and frequency matched controls (n = 1910, and 1493 respectively) were recruited. Detailed data on habitual sleep duration, quality, timing, and daytime napping (“siesta”) were collected at recruitment. Additional data on sleep habits during both the previous year and at age 40 years were also subsequently captured. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) were estimated. There were no associations of habitual sleep duration (h), timing of sleep, or any or specific sleep problems, and either breast and prostate cancer risk. There was a significant positive association of ever taking habitual siestas at recruitment and breast cancer risk (OR = 1.22, 95% CI 1.06–1.42), which strengthened with increased frequency or duration. There were also significant positive associations observed for both breast and prostate cancer, among those reporting recent sleep problems, but not sleep problems at age 40 years, in a subsequent circadian questionnaire. Adverse associations with siesta and disturbed sleep during the previous year likely reflect symptoms of developing/diagnosed cancer and comorbidities. Overall, there was no clear association between various sleep characteristics and breast or prostate cancer risk observed.

BackgroundIn Spain, differences in the prevalence of obesity and excess weight according to sex and sociodemographic factors have been described at the national level, although current data do not allow to delve into geographical differences for these conditions. The aim was to estimate national and regional prevalences of adult obesity and excess weight in Spain by sex and sociodemographic characteristics, and to explore difference sources of inequalities in its distribution, as well as its geographical pattern.MethodENE-COVID study was a nationwide representative seroepidemiological survey with 57,131 participants. Residents in 35,893 households were selected from municipal rolls using a two-stage random sampling stratified by province and municipality size (April–June 2020). Participants (77.0% of contacted individuals) answered a questionnaire which collected self-reported weight and height, as well as different socioeconomic variables, that allowed estimating crude and standardized prevalences of adult obesity and excess weight.ResultsCrude prevalences of obesity and excess weight were higher in men (obesity: 19.3% vs. 18.0%; excess weight: 63.7% vs. 48.4%), while severe obesity was more prevalent in women (4.5% vs. 5.3%). These prevalences increased with age and disability, and decreased with education, census tract income and municipality size. Differences by educational level, relative census income, nationality or disability were clearly higher among women. Obesity by province ranged 13.3–27.4% in men and 11.4–28.1% in women; excess weight ranged 57.2–76.0% in men and 38.9–59.5% in women. The highest prevalences were located in the southern half of the country and some north-western provinces. Sociodemographic characteristics only explained a small part of the observed geographical variability (25.2% obesity).ConclusionObesity and overweight have a high prevalence in Spain, with notable geographical and sex differences. Socioeconomic inequalities are stronger among women. The observed geographical variability suggests the need to implement regional and local interventions to effectively address this public health problem.

Summary: Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett’s oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. Funding: German Research Foundation (DFG).

IntroductionThe protection of children is a major driver of behavior among those in charge of their care. We evaluated whether compliance with preventive measures against SARS-CoV-2 infection among adults living with children was different from that of those not living with them, in 2020.MethodsWe used the COSMO-SPAIN (N = 867) and the nationally representative ENE-COVID (N = 29,926) surveys to estimate prevalence of compliance (95% confidence interval). Logistic model based standardization methods were applied to estimate standardized prevalence differences (SPrD) to the overall distribution of age, sex, education, history of COVID-19, and residence of other >60 yrs in the household.ResultsWe observed that adults living with children more frequently avoided bars (SPrDENE−COVID: 4.2%; 95% CI: 2.3–6.1), crowded places (SPrDCOSMO: 8.0%; 95% CI: 0.6–15.1) and did not use public transportation (SPrDENE−COVID: 4.9%; 95% CI: 3.0–6.7). They were also more worried about work and family conciliation (SPrDCOSMO: 12.2%; 95% CI: 4.8–19.5) and about closure of education centers (SPrDCOSMO: 26.5%; 95% CI: 19.4–33.6).DiscussionIn general, adults living with children adopted slightly more frequently social distancing measures.

Background: Toenails are commonly used as biomarkers of exposure to zinc (Zn), but there is scarce information about their relationship with sources of exposure to Zn. Objectives: To investigate the main determinants of toenail Zn, including selected sources of environmental exposure to Zn and individual genetic variability in Zn metabolism. Methods: We determined toenail Zn by inductively coupled plasma mass spectrometry in 3,448 general population controls from the MultiCase-Control study MCC-Spain. We assessed dietary and supplement Zn intake using food frequency questionnaires, residential proximity to Zn-emitting industries and residential topsoil Zn levels through interpolation methods. We constructed a polygenic score of genetic variability based on 81 single nucleotide polymorphisms in genes involved in Zn metabolism. Geometric mean ratios of toenail Zn across categories of each determinant were estimated from multivariate linear regression models on log-transformed toenail Zn. Results: Geometric mean toenail Zn was 104.1 µg/g in men and 100.3 µg/g in women. Geometric mean toenail Zn levels were 7 % lower (95 % confidence interval 1–13 %) in men older than 69 years and those in the upper tertile of fibre intake, and 9 % higher (3–16 %) in smoking men. Women residing within 3 km from Zn-emitting industries had 4 % higher geometric mean toenail Zn levels (0–9 %). Dietary Zn intake and polygenic score were unrelated to toenail Zn. Overall, the available determinants only explained 9.3 % of toenail Zn variability in men and 4.8 % in women. Discussion: Sociodemographic factors, lifestyle, diet, and environmental exposure explained little of the individual variability of toenail Zn in the study population. The available genetic variants related to Zn metabolism were not associated with toenail Zn.

Introduction There are gaps in the evidence base of tumour classification despite being essential for cancer diagnosis, treatment and patient care. The WHO in charge of the production of an updated international classification, the WHO Classification of Tumours (WCT), aims to adapt evidence gap map (EGM) methodology to inform future editions of the WCT, by providing a visual summary of the existing evidence.Methods and analysis Bibliographical references used in the WCT fifth edition of Tumours of the Lung (Thoracic Tumours volume) will be used as search results of a literature search. A descriptive analysis of the cited evidence for tumour types and descriptors will be drafted and plotted in EPPI-Reviewer to develop a visual evidence map. The resulting EGM will reflect the number of cited studies in the size of the spheres, and the level of evidence by applying a four-colour code (red=low level evidence, orange=moderate level, green=high level and blue=unclassifiable). Overview of the findings will be provided in narrative form and a report will discuss the overall stage of cited research in the WCT and will include analysis of gaps, under-researched categories of tumour descriptors and pockets of low-level evidence.Ethics and dissemination No ethics approval will be required as this is a study of previously published material. Findings of the EGM will be published and used to guide editors, stakeholders and researchers for future research planning and related decision-making, especially for the development of future editions of the WCT.PROSPERO registration number CRD42022302327.

Background Longer time intervals to diagnosis and treatment are associated with worse survival for various types of cancer. The patient, diagnostic, and treatment intervals are considered core indicators for early diagnosis and treatment. This review estimated the median duration of these intervals for various types of cancer and compared it across high- and lower-income countries. Methods and findings We conducted a systematic review with meta-analysis (prospectively registered protocol CRD42020200752). Three databases (MEDLINE, Embase, and Web of Science) and information sources including grey literature (Google Scholar, OpenGrey, EThOS, ProQuest Dissertations & Theses) were searched. Eligible articles were published during 2009 to 2022 and reported the duration of the following intervals in adult patients diagnosed with primary symptomatic cancer: patient interval (from the onset of symptoms to first presentation to a healthcare professional), diagnostic interval (from first presentation to diagnosis), and treatment interval (from diagnosis to treatment start). Interval duration was recorded in days and study medians were combined in a pooled estimate with 95% confidence intervals (CIs). The methodological quality of studies was assessed using the Aarhus checklist. A total of 410 articles representing 68 countries and reporting on 5,537,594 patients were included. The majority of articles reported data from high-income countries (n = 294, 72%), with 116 (28%) reporting data from lower-income countries. Pooled meta-analytic estimates were possible for 38 types of cancer. The majority of studies were conducted on patients with breast, lung, colorectal, and head and neck cancer. In studies from high-income countries, pooled median patient intervals generally did not exceed a month for most cancers. However, in studies from lower-income countries, patient intervals were consistently 1.5 to 4 times longer for almost all cancer sites. The majority of data on the diagnostic and treatment intervals came from high-income countries. Across both high- and lower-income countries, the longest diagnostic intervals were observed for hematological (71 days [95% CI 52 to 85], e.g., myelomas (83 days [47 to 145])), genitourinary (58 days [50 to 77], e.g., prostate (85 days [57 to 112])), and digestive/gastrointestinal (57 days [45 to 67], e.g., colorectal (63 days [48 to 78])) cancers. Similarly, the longest treatment intervals were observed for genitourinary (57 days [45 to 66], e.g., prostate (75 days [61 to 87])) and gynecological (46 days [38 to 54], e.g., cervical (69 days [45 to 108]) cancers. In studies from high-income countries, the implementation of cancer-directed policies was associated with shorter patient and diagnostic intervals for several cancers. This review included a large number of studies conducted worldwide but is limited by survivor bias and the inherent complexity and many possible biases in the measurement of time points and intervals in the cancer treatment pathway. In addition, the subintervals that compose the diagnostic interval (e.g., primary care interval, referral to diagnosis interval) were not considered. Conclusions These results identify the cancers where diagnosis and treatment initiation may take the longest and reveal the extent of global disparities in early diagnosis and treatment. Efforts should be made to reduce help-seeking times for cancer symptoms in lower-income countries. Estimates for the diagnostic and treatment intervals came mostly from high-income countries that have powerful health information systems in place to record such information. Dafina Petrova and colleagues review the median duration of patient, diagnostic, and treatment intervals in adult patients with various types of cancer across high and lower-income countries. Author summary Why was this study done? Cancer is a leading cause of death globally and timely diagnosis and treatment are considered essential for improving cancer outcomes. Three main intervals describe the time patients spend in the pathway to treatment of cancer: the patient interval (from symptom start to first presentation to a healthcare professional), the diagnostic interval (from first presentation to diagnosis), and the treatment interval (from diagnosis to the start of treatment). The duration of these intervals could vary greatly depending on the type of cancer and the socioeconomic level of the country. What did the researchers do and find? We conducted a systematic review with meta-analysis of the duration of the patient, diagnostic, and treatment intervals in adult patients with diverse types of cancer. We included 410 articles representing 68 countries and reporting on 5,537,594 patients; the majority of articles reported data from high-income countries (72%), with only 28% reporting data from lower-income countries. Patient intervals in studies from lower-income countries were consistently 1.5 to 4 times longer that patient intervals from studies from high-income countries for almost all cancer sites. The majority of data on the diagnostic and treatment intervals came from high-income countries, and there was large variation according to the type of cancer. What do these findings mean? These results identify the cancers where diagnosis and treatment initiation may take the longest and reveal important global disparities in early diagnosis and treatment. Efforts should be made to reduce help-seeking times for cancer symptoms in lower-income countries and conduct more research in lower-income contexts, especially on the intervals to diagnosis and treatment. This review summarized a large number of studies conducted worldwide but is limited by biases that could arise due to patient selection (e.g., only patients who survived a certain amount of time) and the difficulty of accurately measuring time intervals for past events.

BackgroundLonger time intervals to diagnosis and treatment are associated with worse survival for various types of cancer. The patient, diagnostic, and treatment intervals are considered core indicators for early diagnosis and treatment. This review estimated the median duration of these intervals for various types of cancer and compared it across high- and lower-income countries.Methods and findingsWe conducted a systematic review with meta-analysis (prospectively registered protocol CRD42020200752). Three databases (MEDLINE, Embase, and Web of Science) and information sources including grey literature (Google Scholar, OpenGrey, EThOS, ProQuest Dissertations & Theses) were searched. Eligible articles were published during 2009 to 2022 and reported the duration of the following intervals in adult patients diagnosed with primary symptomatic cancer: patient interval (from the onset of symptoms to first presentation to a healthcare professional), diagnostic interval (from first presentation to diagnosis), and treatment interval (from diagnosis to treatment start). Interval duration was recorded in days and study medians were combined in a pooled estimate with 95% confidence intervals (CIs). The methodological quality of studies was assessed using the Aarhus checklist. A total of 410 articles representing 68 countries and reporting on 5,537,594 patients were included. The majority of articles reported data from high-income countries (n = 294, 72%), with 116 (28%) reporting data from lower-income countries. Pooled meta-analytic estimates were possible for 38 types of cancer. The majority of studies were conducted on patients with breast, lung, colorectal, and head and neck cancer. In studies from high-income countries, pooled median patient intervals generally did not exceed a month for most cancers. However, in studies from lower-income countries, patient intervals were consistently 1.5 to 4 times longer for almost all cancer sites. The majority of data on the diagnostic and treatment intervals came from high-income countries. Across both high- and lower-income countries, the longest diagnostic intervals were observed for hematological (71 days [95% CI 52 to 85], e.g., myelomas (83 days [47 to 145])), genitourinary (58 days [50 to 77], e.g., prostate (85 days [57 to 112])), and digestive/gastrointestinal (57 days [45 to 67], e.g., colorectal (63 days [48 to 78])) cancers. Similarly, the longest treatment intervals were observed for genitourinary (57 days [45 to 66], e.g., prostate (75 days [61 to 87])) and gynecological (46 days [38 to 54], e.g., cervical (69 days [45 to 108]) cancers. In studies from high-income countries, the implementation of cancer-directed policies was associated with shorter patient and diagnostic intervals for several cancers. This review included a large number of studies conducted worldwide but is limited by survivor bias and the inherent complexity and many possible biases in the measurement of time points and intervals in the cancer treatment pathway. In addition, the subintervals that compose the diagnostic interval (e.g., primary care interval, referral to diagnosis interval) were not considered.ConclusionsThese results identify the cancers where diagnosis and treatment initiation may take the longest and reveal the extent of global disparities in early diagnosis and treatment. Efforts should be made to reduce help-seeking times for cancer symptoms in lower-income countries. Estimates for the diagnostic and treatment intervals came mostly from high-income countries that have powerful health information systems in place to record such information.

Circadian nutritional behaviors, defined by the daily eating/fasting cycle, have been linked with breast cancer. This study aimed to further disentangle the association of nighttime fasting duration and time of breakfast with breast cancer risk. We analyzed data from 1,181 breast cancer cases and 1,326 population controls from the Spanish multicase-control study (MCC-Spain), 2008–2013. We collected circadian nutritional behaviors at mid-age via a telephonic interview. We applied logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of nighttime fasting duration and time of breakfast with breast cancer risk in all women and stratified by menopausal status. Models were adjusted for age, center, education, family history of breast cancer, age at menarche, number of children, breastfeeding, age at first child, body mass index (BMI), contraceptive use, and hormonal replacement therapy (HRT). A later time of breakfast was associated with a non-significant increased risk of breast cancer (OR = 1.05, 95% CI: 0.95–1.16, per hour increase). This association was stronger among premenopausal women, among whom each hour later, the time of breakfast was associated with an 18% increase in breast cancer risk (OR = 1.18, 95% CI: 1.01–1.40). The association was not observed in postmenopausal women. We did not observe an association between nighttime fasting duration and breast cancer risk after adjusting for the time of breakfast. In this study, late breakfast was associated with increased breast cancer risk, especially among premenopausal women, compared with early breakfast. Aside from nutritional quality, circadian nutritional behaviors should be further studied in relation to cancer.

BackgroundA healthy diet when approaching menopause could prevent some of the symptoms associated with the climacteric. Few studies examine adherence to current healthy dietary recommendations in middle-aged premenopausal women. Our objective was to analyze the diet quality and the adherence to the Spanish Society of Community Nutrition (SENC) dietary recommendations in middle-aged Spanish premenopausal women, and to identify the associated sociodemographic and lifestyle factors.MethodsThis is a cross-sectional study based on 1251 premenopausal women, aged 39–50, who attended to Madrid City Council Medical Diagnostic Center. Women completed an epidemiological and a food frequency questionnaire. Degree of adherence to the SENC recommendations was estimated with a score that evaluated null (0 points) and full (1 point) adherence of each specific recommendation. Associations were explored using an ordinal logistic multivariable regression model.ResultsRegarding food groups, the worst adherence was found for sweets, red/processed meat, olive oil and eggs. Most of the participants exceeded the recommended caloric intake from proteins and fats, and practically all of them showed vitamin D intake deficiency. The overall score ranged from 2 to 12 (out of 15), with a median of 6.0 (interquartile range: 5.0–7.0). Former smokers (OR: 1.38; 95%CI: 1.08–1.78), as well as those with higher educational level (ORSSecondary:1.68; 95%CI: 0.97–2.93, ORUniversity:1.82; 95%IC: 1.05–3.14), with two or more children (OR: 1.31; 95%IC: 1.00-1.72), with higher caloric intake (OR>2188.2kcal/day: 8.22; 95%CI: 6.19–10.92) and with greater physical activity (OR≥21METS−h/week: 1.29; 95%CI: 0.95-1.76) showed greater adherence.ConclusionsAlmost two-thirds of middle-aged premenopausal participants showed low or moderate compliance with SENC recommendations. Education, smoking, parity, and physical activity were associated with the degree of adherence to these recommendations.

Resumen: La incidencia y la mortalidad brindan información sobre la carga de la morbilidad del cáncer y los años potenciales de vida perdidos debido al cáncer. Se ha desarrollado el Índice de Privación (IP) como una medida estandarizada para medir la privación socioeconómica en España a nivel de sección censal. Además, se puede combinar la información del IP con variables ecológicas poblacionales y los datos de los Estudios Europeos de Alta Resolución en Cáncer. El objetivo de este estudio es caracterizar las desigualdades socioeconómicas en la incidencia, el exceso de mortalidad, la mortalidad prematura y la supervivencia neta para tres de los cánceres más incidentes (pulmón, colon-recto y mama) en España usando el IP. Este estudio nacional multinivel de base poblacional evaluará el impacto de las desigualdades socioeconómicas. Se usarán el análisis espacial, la modelización multinivel, la supervivencia neta y la evaluación del impacto económico. Los resultados serán útiles para el apoyo a la toma de decisiones y la planificación y la gestión de intervenciones en salud pública destinadas a reducir el impacto de las desigualdades socioeconómicas en el diagnóstico y el pronóstico de los pacientes de cáncer en España. Abstract: Incidence and mortality provide information on the burden of cancer morbidity and the potential years of life lost due to cancer. The Spanish Deprivation Index (SDI) has been developed as a standardized measure to study socioeconomic deprivation in Spain at the census tract level. In addition, SDI information can be combined with ecological variables at the population level and data from the High-Resolution European Studies in Cancer. The aim of this study is to characterize socioeconomic inequalities in incidence, excess mortality, premature mortality and net survival for three of the most incident cancers (lung, colon-rectum and breast) in Spain using the SDI. This national population-based study will assess the impact of socioeconomic inequalities using a multilevel modelling approach. Spatial analysis, multilevel modeling, net survival and economic impact assessment will be used. The results will be useful for supporting decision-making, planning, and management of public health interventions aimed at reducing the impact of socioeconomic inequalities in the diagnosis and prognosis of cancer patients in Spain.

Abstract 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

Abstract This study evaluates the impact of breast cancer (BC) in health related quality of life (HRQL) and in psychological distress (PD) during the initial phases of the disease and looks for contributing factors. A multicentric case-control study, EpiGEICAM, was carried out. Incident BC cases and age- and residence- matched controls were included. Clinical, epidemiological, HRQL (SF-36) and PD information (GHQ-28) was collected. We used multivariable logistic regression models to estimate OR of low HRQL and of PD in cases compared to controls, and to identify factors associated with low HRQL and with PD. Among 896 BC cases and 890 control women, cases had poorer scores than both, the reference population and the control group, in all SF-36 scales. BC women with lower education, younger, active workers, never smokers, those with comorbidities, in stage IV and with surgical treatment had lower physical HRQL; factors associated with low mental HRQL were dissatisfaction with social support, being current smoker and having children. Cases had a fivefold increased odds of PD compared to controls. Managing comorbidities and trying to promote social support, especially in younger and less educated women, could improve well-being of BC patients.

Abstract Background The association between socioeconomic level and reproductive factors has been widely studied. For example, it is well known that women with lower socioeconomic status (SES) tend to have more children, the age at first-born being earlier. However, less is known about to what extent the great socioeconomic changes occurred in a country (Spain) could modify women reproductive factors. The main purpose of this article is to analyze the influence of individual and contextual socioeconomic levels on reproductive factors in Spanish women, and to explore whether this influence has changed over the last decades. Methods We performed a cross-sectional design using data from 2038 women recruited as population-based controls in an MCC-Spain case-control study. Results Higher parent’s economic level, education level, occupational level and lower urban vulnerability were associated with higher age at first delivery and lower number of pregnancies. These associations were stronger for women born after 1950: women with unfinished primary education had their first delivery 6 years before women with high education if they were born after 1950 (23.4 vs. 29.8 years) but only 3 years before if they were born before 1950 (25.7 vs. 28.0 years). For women born after 1950, the number of pregnancies dropped from 2.1 (unfinished primary school) to 1.7 (high education), whereas it remained almost unchanged in women born before 1950. Conclusions Reproductive behavior was associated with both individual and area-level socio-economic indicators. Such association was stronger for women born after 1950 regarding age at first delivery and number of pregnancies and for women born before 1950 regarding consumption of hormonal contraceptives or postmenopausal therapy.

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

Background: 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. Objectives: We investigated whether occupational exposure to alkylphenolic compounds is associated with breast and prostate cancer. Methods: 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. Conclusions: 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. Keywords: Alkylphenols, Alkylphenolic compounds, Job-exposure matrix, Breast cancer, Prostate cancer, Occupational exposure

The aim of this study was to explore the association between three previously identified dietary patterns (Western, Prudent, and Mediterranean) and colorectal cancer (CRC) risk by sex and cancer subtype. The Spanish cohort of the European Prospective Investigation into Cancer and Nutrition study provided dietary and epidemiological information from 15,629 men and 25,808 women recruited between 1992 and 1996. Among them, 568 CRC cases and 3289 deaths were identified during a median follow-up of 16.98 years. The associations between adherence to the three dietary patterns and CRC risk (overall, by sex, and by tumour location: proximal and distal colon and rectum) were investigated by fitting multivariate Cox proportional hazards regression models stratified by study centre and age. Possible heterogeneity of the effects by sex and follow-up time (1–10 vs. ≥10 years) was also explored. While no clear effect of the Prudent dietary pattern on CRC risk was found, a suggestive detrimental effect of the Western dietary pattern was observed, especially during the first 10 years of follow-up (HR1SD-increase (95% CI): 1.17 (0.99–1.37)), among females (HR1SD-increase (95% CI): 1.31 (1.06–1.61)), and for rectal cancer (HR1SD-increase (95% CI): 1.38 (1.03–1.84)). In addition, high adherence to the Mediterranean pattern seemed to protect against CRC, especially when restricting the analyses to the first 10 years of follow-up (HR1SD-increase (95% CI): 0.84 (0.73–0.98)), among males (HR1SD-increase (95% CI): 0.80 (0.65–0.98)), and specifically against distal colon cancer (HR1SD-increase (95% CI): 0.81 (0.63–1.03)). In conclusion, low adherence to the Western diet and high adherence to the Mediterranean dietary pattern could prevent CRC, especially distal colon and rectal cancer.

Breast density assessed from digital mammograms is a known biomarker related to a higher risk of developing breast cancer. Supervised learning algorithms have been implemented to determine this. However, the performance of these algorithms depends on the quality of the ground-truth information, which expert readers usually provide. These expert labels are noisy approximations to the ground truth, as there is both intra- and inter-observer variability among them. Thus, it is crucial to provide a reliable method to measure breast density from mammograms. This paper presents a fully automated method based on deep learning to estimate breast density, including breast detection, pectoral muscle exclusion, and dense tissue segmentation. We propose a novel confusion matrix (CM)—YNet model for the segmentation step. This architecture includes networks to model each radiologist’s noisy label and gives the estimated ground-truth segmentation as well as two parameters that allow interaction with a threshold-based labeling tool. A multi-center study involving 1785 women whose “for presentation” mammograms were obtained from 11 different medical facilities was performed. A total of 2496 mammograms were used as the training corpus, and 844 formed the testing corpus. Additionally, we included a totally independent dataset from a different center, composed of 381 women with one image per patient. Each mammogram was labeled independently by two expert radiologists using a threshold-based tool. The implemented CM-Ynet model achieved the highest DICE score averaged over both test datasets (0.82±0.14) when compared to the closest dense-tissue segmentation assessment from both radiologists. The level of concordance between the two radiologists showed a DICE score of 0.76±0.17. An automatic breast density estimator based on deep learning exhibited higher performance when compared with two experienced radiologists. This suggests that modeling each radiologist’s label allows for better estimation of the unknown ground-truth segmentation. The advantage of the proposed model is that it also provides the threshold parameters that enable user interaction with a threshold-based tool.

Objectives: To explore the association of colorectal cancer with environmental solar radiation and sun exposure behavior, considering phenotypic variables (eye color, hair color and skin phenotype), dietary intake of vitamin D and calcium, and socio-demographic factors. Study design: Multicenter population-based frequency matched case-control study in Spain (MCC-Spain), with 2140 CRC cases and 3950 controls. Methods: Data were obtained through personal interviews using a structured epidemiological questionnaire that included socio-demographic data, residential history, environmental exposures, behavior, phenotypic and dietary information. An environmental-lifetime sun exposure score was constructed combining residential history and average daily solar radiation, direct and diffuse. Logistic regression was used to explore the association between different variables. A structural equation model was used to verify the associations of the conceptual model. Results: We found a lower risk of CRC in subjects frequently exposed to sunlight during the previous summer and skin burning due to sun exposure. No association was observed in relation to the residential solar radiation scores. Subjects with light eye or light hair colors had a lower risk of CRC that those with darker colors. Dietary calcium and vitamin D were also protective factors, but not in the multivariate model. The structural equation model analysis suggested that higher sun exposure was associated with a decreased risk of CRC, as well as dietary intake of calcium and vitamin D, and these factors are correlated among themselves and with environmental solar radiation and skin phenotypes. Conclusion: The results agree with previous observations that sun exposure, dietary vitamin D and calcium intake, and serum 25(OH)D concentration reduce the risk of CRC and indicate that these factors may be relevant for cancer prevention. Keywords: Colorectal cancer, Sunlight, Calcium, Vitamin D, Skin phenotype

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.

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 self-reported 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. Keywords: Self-reported perception, Residential proximity, Case-control study, Sensitivity, Specificity, AUC, Industrial pollution, MCC-Spain

Abstract 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% (

Abstract Background The incidence of breast cancer has increased since the 1970s. Despite favorable trends in prognosis, the role of changes in clinical practice and the introduction of screening remain controversial. We examined breast cancer trends to shed light on their determinants. Methods Data were obtained for 8502 new cases of breast cancer in women between 1985 and 2012 from a population-based cancer registry in Granada (southern Spain), and for 2470 breast cancer deaths registered by the Andalusian Institute of Statistics. Joinpoint regression analyses of incidence and mortality rates were obtained. Observed and net survival rates were calculated for 1, 3 and 5 years. The results are reported here for overall survival and survival stratified by age group and tumor stage. Results Overall, age-adjusted (European Standard Population) incidence rates increased from 48.0 cases × 100,000 women in 1985–1989 to 83.4 in 2008–2012, with an annual percentage change (APC) of 2.5% (95%CI, 2.1–2.9) for 1985–2012. The greatest increase was in women younger than 40 years (APC 3.5, 95%CI, 2.4–4.8). For 2000–2012 the incidence trend increased only for stage I tumors (APC 3.8, 95%CI, 1.9–5.8). Overall age-adjusted breast cancer mortality decreased (APC − 1, 95%CI, − 1.4 – − 0.5), as did mortality in the 50–69 year age group (APC − 1.3, 95%CI, − 2.2 – − 0.4). Age-standardized net survival increased from 67.5% at 5 years in 1985–1989 to 83.7% in 2010–2012. All age groups younger than 70 years showed a similar evolution. Five-year net survival rates were 96.6% for patients with tumors diagnosed in stage I, 88.2% for stage II, 62.5% for stage III and 23.3% for stage IV. Conclusions Breast cancer incidence is increasing – a reflection of the evolution of risk factors and increasing diagnostic pressure. After screening was introduced, the incidence of stage I tumors increased, with no decrease in the incidence of more advanced stages. Reductions were seen for overall mortality and mortality in the 50–69 year age group, but no changes were found after screening implementation. Survival trends have evolved favorably except for the 70–84 year age group and for metastatic tumors.

Abstract Background Pancreatic cancer is acquiring increasing prominence as a cause of cancer death in the population. The purpose of this study was to analyze long-term pancreatic cancer mortality trends in Spain and evaluate the independent effects of age, death period and birth cohort on these trends. Methods Population and mortality data for the period 1952–2012 were obtained from the Spanish National Statistics Institute. Pancreatic cancer deaths were identified using the International Classification of Diseases ICD-6 to ICD-9 (157 code) and ICD-10 (C25 code). Age-specific and age-adjusted mortality rates were computed by sex, region and five-year period. Changes in pancreatic cancer mortality trends were evaluated using joinpoint regression analyses by sex and region. Age-period-cohort log-linear models were fitted separately for each sex, and segmented regression models were used to detect changes in period- and cohort-effect curvatures. Results In men, rates increased by 4.1% per annum from 1975 until the mid-1980s and by 1.1% thereafter. In women, there was an increase of 3.6% per annum until the late 1980s, and 1.4% per annum from 1987 to 2012. With reference to the cohort effects, there was an increase in mortality until the generations born in the 1950s in men and a subsequent decline detected by the change point in 1960. A similar trend was observed in women, but the change point occurred 10 years later than in men. Conclusions Pancreatic cancer mortality increased over the study period in both sexes and all regions. An important rise in rates -around 4% annually- was registered until the 1980s, and upward trends were more moderate subsequently. The differences among sexes in trends in younger generations may be linked to different past prevalence of exposure to some risk factors, particularly tobacco, which underwent an earlier decrease in men than in women.

Abstract Background Reproductive factors are well known risk factors for breast cancer; however, little is known about how genetic variants in hormonal pathways interact with that relationship. Methods One thousand one hundred thirty nine cases of breast cancer in women and 1322 frequency-matched controls were compared. Genetic variants in hormonal pathways (identified in the Kyoto Encyclopedia of Genes and Genomes) were screened according to their relationship with breast cancer using the Cochran-Armitage statistic. Information on reproductive factors was obtained using a face-to-face questionnaire. The interaction among the selected genetic variants and reproductive factors was tested with logistic regression. Results Concerning C allele in rs2229712, compared to nulliparity in non-carriers the ORs for 1–2 and > 2 deliveries were 0.48 (0.28–0.81) and 0.34 (0.19–0.59), and in C carriers they were 0.92 (0.42–1.98) and 0.71 (0.31–1.61). Similar results were found in women carrying the C allele in rs1269851. Carriers of Allele T in rs35652107 and allele C in rs6018027 had the delivery number effect more pronounced. Conclusions The number of deliveries had a dose-response protective effect on breast cancer; women carrying C allele in rs2229712 did not benefit from this protective effect.

The most representative indicator of vitamin D status in clinical practice is 25(OH)D3, but new biomarkers could improve the assessment of vitamin D status and metabolism. The objective of this study is to investigate the association of serum vitamin D metabolites and vitamin D metabolite ratios (VMRs) with potentially influential factors in premenopausal women. This is a cross-sectional study based on 1422 women, aged 39–50, recruited from a Madrid Medical Diagnostic Center. Participants answered an epidemiological and a food frequency questionnaire. Serum vitamin D metabolites were determined using an SPE–LC–MS/MS platform. The association between participant’s characteristics, vitamin D metabolites, and VMRs was quantified by multiple linear regression models. Mean 25(OH)D3 concentration was 49.2 + 18.9 nmol/L, with greater deficits among obese, nulliparous, dark-skinned women, and with less sun exposure. A lower R2 ratio (1,25(OH)2D3/25(OH)D3) and a higher R4 (24,25(OH)2D3/1,25(OH)2D3) were observed in nulliparous women, with high sun exposure, and those with low caloric intake or high consumption of calcium, vitamin D supplements, or alcohol. Nulliparous women had lower R1 (25(OH)D3/Vit D3) and R3 (24,25(OH)2D3/25(OH)D3), and older women showed lower R3 and R4. Vitamin D status modified the association of the VMRs with seasons. VMRs can be complementary indicators of vitamin D status and its endogenous metabolism, and reveal the influence of certain individual characteristics on the expression of hydroxylase enzymes.

Nighttime fasting has been inconclusively associated with a reduced risk of cancer. The purpose of this study was to investigate this association in relation to prostate cancer risk. We examined data from 607 prostate cancer cases and 848 population controls who had never worked in night shift work from the Spanish multicase-control (MCC) study, 2008–2013. Through an interview, we collected circadian information on meal timing at mid-age. We estimated odds ratios (OR) and 95% confidence intervals (CI) with unconditional logistic regression. After controlling for time of breakfast, fasting for more than 11 h overnight (the median duration among controls) was associated with a reduced risk of prostate cancer compared to those fasting for 11 h or less (OR = 0.77, 95% 0.54–1.07). Combining a long nighttime fasting and an early breakfast was associated with a lower risk of prostate cancer compared to a short nighttime fasting and a late breakfast (OR = 0.54, 95% CI 0.27–1.04). This study suggests that a prolonged nighttime fasting duration and an early breakfast may be associated with a lower risk of prostate cancer. Findings should be interpreted cautiously and add to growing evidence on the importance of chrononutrition in relation to cancer risk.

Abstract 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.

Abstract Prostate cancer (PCa) is the second most common cancer among men worldwide. Its etiology remains largely unknown compared to other common cancers. We have developed a risk stratification model combining environmental factors with family history and genetic susceptibility. 818 PCa cases and 1,006 healthy controls were compared. Subjects were interviewed on major lifestyle factors and family history. Fifty-six PCa susceptibility SNPs were genotyped. Risk models based on logistic regression were developed to combine environmental factors, family history and a genetic risk score. In the whole model, compared with subjects with low risk (reference category, decile 1), those carrying an intermediate risk (decile 5) had a 265% increase in PCa risk (OR = 3.65, 95% CI 2.26 to 5.91). The genetic risk score had an area under the ROC curve (AUROC) of 0.66 (95% CI 0.63 to 0.68). When adding the environmental score and family history to the genetic risk score, the AUROC increased by 0.05, reaching 0.71 (95% CI 0.69 to 0.74). Genetic susceptibility has a stronger risk value of the prediction that modifiable risk factors. While the added value of each SNP is small, the combination of 56 SNPs adds to the predictive ability of the risk model.

BACKGROUND:Prostate cancer (PC) primarily affects elderly men. However, the specific features of cases diagnosed at younger ages (

In Spain, the health crisis caused by the COVID-19 pandemic led to the declaration of a state of alarm in the whole country in 2020; in this context, a nationwide lockdown was implemented, potentially altering the dietary habits of the population. The aims of this study were to describe the diet and its nutritional quality in Spanish households during the first COVID-19 epidemic wave and to compare them with the same period in 2019. Data on monthly foods and beverages household purchases in 2019 and 2020 were obtained from the nationwide Food Consumption Surveys. In April, there was an average increase, compared with 2019, of more than 40% for all food groups, with significant peaks in: alcoholic beverages (75%), appetizers (60%), eggs (59%), sugar and sweets (52%), and vegetables (50%). In March, the greatest peak was for pulses, with a 63% increment. The mean energy value of purchased foods in April was 2801 kcal/person/day, corresponding to an increase of 771 kcal/person/day (+38%), compared to the same month of 2019 (March and May: +520 kcal (+26%), June: +343 kcal (+18%)). Regarding nutrient density, there was a reduction in calcium, iodine, zinc, selenium, riboflavin, vitamins B12, D, A, especially retinol, and an increase in fibre, sodium, folic acid, carotenes and vitamin E. Alcohol content per 1000 kcal increased by more than 20% from April to July. Food purchase patterns in Spanish households changed during lockdown and after it, with no appreciable improvement in the quality of the diet.

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 different regions of Spain. We included 2700 controls and 329 GC cases. Odds ratios (ORs) were calculated using mixed effects 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 differences 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.

This study evaluates whether serum phospholipids fatty acids (PL-FAs) and markers of their endogenous metabolism are associated with breast cancer (BC) subtypes. EpiGEICAM is a Spanish multicenter matched case-control study. A lifestyle and food frequency questionnaire was completed by 1017 BC cases and healthy women pairs. Serum PL-FA percentages were measured by gas chromatography-mass spectrometry. Conditional and multinomial logistic regression models were used to quantify the association of PL-FA tertiles with BC risk, overall and by pathological subtype (luminal, HER2+ and triple negative). Stratified analyses by body mass index and menopausal status were also performed. Serum PL-FAs were measured in 795 (78%) pairs. Women with high serum levels of stearic acid (odds ratio (OR)T3vsT1 = 0.44; 95% confidence interval (CI) = 0.30–0.66), linoleic acid (ORT3vsT1 = 0.66; 95% CI = 0.49–0.90) and arachidonic to dihomo-γ-linolenic acid ratio (OR T3vsT1 = 0.64; 95% CI = 0.48–0.84) presented lower BC risk. Participants with high concentrations of palmitoleic acid (ORT3vsT1 = 1.65; 95% CI = 1.20–2.26), trans-ruminant palmitelaidic acid (ORT3vsT1 = 1.51; 95% CI = 1.12–2.02), trans-industrial elaidic acid (ORT3vsT1 = 1.52; 95% CI = 1.14–2.03), and high oleic to stearic acid ratio (ORT3vsT1 = 2.04; 95% CI = 1.45–2.87) showed higher risk. These associations were similar in all BC pathological subtypes. Our results emphasize the importance of analyzing fatty acids individually, as well as the desaturase activity indices.

This study investigates the still uncertain association between serum phospholipid fatty acids (PL-FA), and anthropometric and adiposity variables. A cross-sectional study was conducted with 1443 Spanish premenopausal women. Participants answered an epidemiological and a food frequency questionnaire. Anthropometric variables were measured using a bioimpedance scale. Serum PL-FAs levels were determined by gas chromatography–mass spectrometry. The association between body mass index (BMI), weight gain, body fat percentage, visceral fat index, and waist circumference with serum PL-FAs and desaturation indices was evaluated using multivariable linear regression models. BMI was positively associated with the relative concentration of saturated fatty acids (SFAs) (β = 0.94, q-val = 0.001), and with palmitoleic, dihomo-γ-linolenic (DGLA), arachidonic (AA) and α-linolenic acids, and was inversely associated with oleic, gondoic, trans-vaccenic, linoleic and γ-linolenic acids. Total fat percentage was positively associated with DGLA and AA, and inversely with linoleic and γ-linolenic acids. Low relative concentrations of some SFAs and high levels of n-6 PUFAs were associated with greater waist circumference. While the oleic/stearic and AA/DGLA acid ratios were inversely associated with BMI, DGLA/linoleic acid ratio was positively related to almost all variables. In addition to BMI, total fat percentage and waist circumference were also associated with certain individual fatty acids.

Diet is a modifiable risk factor for several neoplasms but evidence for chronic lymphocytic leukemia (CLL) is sparse. Previous studies examining the association between single-food items and CLL risk have yielded mixed results, while few studies have been conducted on overall diet, reporting inconclusive findings. This study aimed to evaluate the association between adherence to three dietary patterns and CLL in the multicase-control study (MCC-Spain) study. Anthropometric, sociodemographic, medical and dietary information was collected for 369 CLL cases and 1605 controls. Three validated dietary patterns, Western, Prudent and Mediterranean, were reconstructed in the MCC-Spain data. The association between adherence to each dietary pattern and CLL was assessed, overall and by Rai stage, using mixed logistic regression models adjusted for potential confounders. High adherence to a Western dietary pattern (i.e. high intake of high-fat dairy products, processed meat, refined grains, sweets, caloric drinks, and convenience food) was associated with CLL [ORQ4 vs. Q1=1.63 (95%CI 1.11; 2.39); P-trend=0.02; OR 1-SD increase=1.19 (95%CI: 1.03; 1.37)], independently of Rai stages. No differences in the association were observed according to sex, Body Mass Index, energy intake, tobacco, physical activity, working on a farm, or family history of hematologic malignancies. No associations were observed for Mediterranean and Prudent dietary patterns and CLL. This study provides the first evidence for an association between a Western dietary pattern and CLL, suggesting that a proportion of CLL cases could be prevented by modifying dietary habits. Further research, especially with a prospective design, is warranted to confirm these findings.

INTRODUCTION:Phototype has been associated with an increased risk of prostate cancer, and it is yet unknown if it is related to other hormone-dependent cancers, such as breast cancer or whether this association could be considered causal. METHODS:We examined the association between the phototype and breast and prostate cancers using a Mendelian randomization analysis. We studied 1,738 incident cases of breast cancer and another 817 cases of prostate cancer. To perform a Mendelian randomization analysis on the phototype-cancer relationship, a genetic pigmentation score was required that met the following criteria: (1) the genetic pigmentation score was associated with phototype in controls; (2) the genetic pigmentation score was not associated with confounders in the relationship between phototype and cancer, and (3) the genetic pigmentation score was associated with cancer only through its association with phototype. Once this genetic score is available, the association between genetic pigmentation score and cancer can be identified as the association between phototype and cancer. RESULTS:The association between the genetic pigmentation score and phototype in controls showed that a higher genetic pigmentation score was associated with fair skin, blond hair, blue eyes and the presence of freckles. Applying the Mendelian randomization analysis, we verified that there was no association between the genetic pigmentation score and cancers of the breast and prostate. CONCLUSIONS:Phototype is not associated with breast or prostate cancer.

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.

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.

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.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).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.Both household and recreational physical activities were independently related to lower GAC risk in the MCC-Spain study.

To determine the frequency of breast cancer (BC) patients with hereditary risk features in a wide retrospective cohort of patients in Spain.a retrospective analysis was conducted from 10,638 BC patients diagnosed between 1998 and 2001 in the GEICAM registry "El Álamo III", dividing them into four groups according to modified ESMO and SEOM hereditary cancer risk criteria: Sporadic breast cancer group (R0); Individual risk group (IR); Familial risk group (FR); Individual and familial risk group (IFR) with both individual and familial risk criteria.7,641 patients were evaluable. Of them, 2,252 patients (29.5%) had at least one hereditary risk criteria, being subclassified in: FR 1.105 (14.5%), IR 970 (12.7%), IFR 177 (2.3%). There was a higher frequency of newly diagnosed metastatic patients in the IR group (5.1% vs 3.2%, p = 0.02). In contrast, in RO were lower proportion of big tumors (> T2) (43.8% vs 47.4%, p = 0.023), nodal involvement (43.4% vs 48.1%, p = 0.004) and lower histological grades (20.9% G3 for the R0 vs 29.8%) when compared to patients with any risk criteria.Almost three out of ten BC patients have at least one hereditary risk cancer feature that would warrant further genetic counseling. Patients with hereditary cancer risk seems to be diagnosed with worse prognosis factors.

Fundamentos: El cáncer de mama es el más frecuente en las mujeres. El objetivo del presente estudio fue analizar la incidencia y distribución geográfica del cáncer de mama invasivo en el área de salud de León (ASL). Métodos: Estudio observacional descriptivo en el que se incluyeron mujeres con diagnóstico de neoplasia maligna de mama (CIE-9:174, CIE- 10: C50) del Registro Hospitalario de Tumores del Centro Asistencial Universitario de León, entre 1/1/1996 y 31/12/2010 y con residencia en el ASL. Para el análisis de la distribución espacial se estimaron los riesgos relativos (RR) municipales suavizados mediante el ajuste del modelo de Besag, York y Mollié y sus probabilidades posteriores de que los RR fuesen >1 (PP), utilizando métodos bayesianos. Resultados: Se incluyó un total de 2.379 casos. El número de casos nuevos y las tasas de incidencia brutas en cada trienio fueron de 72,7 (1996-1998) a 101,5 (2008-2010) por 100.000 mujeres. Las tasas a población europea por 100.000 mujeres ascendieron de 58,0 en el primer trienio y a 69,4 en el último. Se observó un incremento anual promedio del 1,3%. Varios municipios del ASL presentaron riesgos superiores al 10 %. Las PP solo fueron superiores a 0,9 en el municipio de León. Conclusiones: Las tasas observadas son de las más bajas de España. Sin embargo, el número de casos y las tasas de incidencia seincrementaron de manera mantenida en el periodo estudiado.

Inflammation and antioxidant capacity have been associated with colorectal and breast cancer. We computed the dietary inflammatory index (DII®), 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:1.60−2.32; p-trend: p-trend: >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: 1.26−1.74; p-trend: