Nitrosyl-heme and Heme Iron Intake from Processed Meats and Risk of Colorectal Cancer in the EPIC-Spain Cohort.

BACKGROUND: The International Agency for Research on Cancer classified processed meats (PM) as "carcinogenic" and red meat as "probably carcinogenic" for humans. The possible relationship between colorectal cancer risk and the mechanisms involved in the carcinogenesis of PMs have not been established yet. Nitrosyl-heme and heme iron have been proposed as potential-related compounds. The aim of this study was to determine the association between nitrosyl-heme and heme iron intake and colorectal cancer risk among participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain study. METHODS: This prospective study included 38,262 men and women from the EPIC-Spain study. Food consumption was assessed using diet history and food composition tables. Heme iron and nitrosyl-heme intake were determined by estimating the intake of PM items and conducting laboratory analyses. HR estimates were obtained by proportional hazard models, stratified by age at recruitment and study center and adjusted for sex, total energy intake, education, smoking, body mass index, waist size, physical activity, lifetime alcohol, fibre, calcium, and familiar colorectal cancer history. RESULTS: During a mean follow-up of 16.7 years, 577 participants were diagnosed with colorectal cancer. We found no overall association between nitrosyl-heme [HRT3vsT1, 0.98; 95% confidence interval (CI), 0.79-1.21] or heme iron intakes (HRT3vsT1, 0.88; 95% CI, 0.70-1.10) with colorectal cancer risk, nor according to tumor subtypes. CONCLUSIONS: Our study found no evidence supporting a link between nitrosyl-heme or heme iron intake and colorectal cancer risk in Spanish subjects. IMPACT: As research on nitrosyl-heme is preliminary, more heterogeneous studies are necessary to provide more convincing evidence on their role in colorectal cancer carcinogenesis.

Complete cancer prevalence in Europe in 2020 by disease duration and country (EUROCARE-6): a population-based study.

BACKGROUND: Cancer survivors-people living with and beyond cancer-are a growing population with different health needs depending on prognosis and time since diagnosis. Despite being increasingly necessary, complete information on cancer prevalence is not systematically available in all European countries. We aimed to fill this gap by analysing population-based cancer registry data from the EUROCARE-6 study. METHODS: In this population-based study, using incidence and follow-up data up to Jan 1, 2013, from 61 cancer registries, complete and limited-duration prevalence by cancer type, sex, and age were estimated for 29 European countries and the 27 countries in the EU (EU27; represented by 22 member states that contributed registry data) using the completeness index method. We focused on 32 malignant cancers defined according to the third edition of the International Classification of Diseases for Oncology, and only the first primary tumour was considered when estimating the prevalence. Prevalence measures are expressed in terms of absolute number of prevalent cases, crude prevalence proportion (reported as percentage or cases per 100 000 resident people), and age-standardised prevalence proportion based on the European Standard Population 2013. We made projections of cancer prevalence proportions up to Jan 1, 2020, using linear regression. FINDINGS: In 2020, 23 711 thousand (95% CI 23 565-23 857) people (5·0% of the population) were estimated to be alive after a cancer diagnosis in Europe, and 22 347 thousand (95% CI 22 210-22 483) in EU27. Cancer survivors were more frequently female (12 818 thousand [95% CI 12 720-12 917]) than male (10 892 thousand [10 785-11 000]). The five leading tumours in female survivors were breast cancer, colorectal cancer, corpus uterine cancer, skin melanoma, and thyroid cancer (crude prevalence proportion from 2270 [95%CI 2248-2292] per 100 000 to 301 [297-305] per 100 000). Prostate cancer, colorectal cancer, urinary bladder cancer, skin melanoma, and kidney cancer were the most common tumours in male survivors (from 1714 [95% CI 1686-1741] per 100 000 to 255 [249-260] per 100 000). The differences in prevalence between countries were large (from 2 to 10 times depending on cancer type), in line with the demographic structure, incidence, and survival patterns. Between 2010 and 2020, the number of prevalent cases increased by 3·5% per year (41% overall), partly due to an ageing population. In 2020, 14 850 thousand (95% CI 14 681-15 018) people were estimated to be alive more than 5 years after diagnosis and 9099 thousand (8909-9288) people were estimated to be alive more than 10 years after diagnosis, representing an increasing proportion of the cancer survivor population. INTERPRETATION: Our findings are useful at the country level in Europe to support evidence-based policies to improve the quality of life, care, and rehabilitation of patients with cancer throughout the disease pathway. Future work includes estimating time to cure by stage at diagnosis in prevalent cases. FUNDING: European Commission.

Metagenomic sequencing, molecular characterization, and Bayesian phylogenetics of imported type 2 vaccine-derived poliovirus, Spain, 2021.

Introduction: In 2021, a type 2 vaccine-derived poliovirus (VDPV2) was isolated from the stool of a patient with acute flaccid paralysis (AFP) admitted to Spain from Senegal. A virological investigation was conducted to characterize and trace the origin of VDPV2. Methods: We used an unbiased metagenomic approach for the whole-genome sequencing of VDPV2 from the stool (pre-treated with chloroform) and from the poliovirus-positive supernatant. Phylogenetic analyses and molecular epidemiological analyses relying on the Bayesian Markov Chain Monte Carlo methodology were used to determine the geographical origin and estimate the date of the initiating dose of the oral poliovirus vaccine for the imported VDPV2. Results: We obtained a high percentage of viral reads per total reads mapped to the poliovirus genome (69.5% for pre-treated stool and 75.8% for isolate) with a great depth of sequencing coverage (5,931 and 11,581, respectively) and complete genome coverage (100%). The two key attenuating mutations in the Sabin 2 strain had reverted (A481G in the 5'UTR and Ile143Thr in VP1). In addition, the genome had a recombinant structure between type-2 poliovirus and an unidentified non-polio enterovirus-C (NPEV-C) strain with a crossover point in the protease-2A genomic region. VP1 phylogenetic analysis revealed that this strain is closely related to VDPV2 strains circulating in Senegal in 2021. According to Bayesian phylogenetics, the most recent common ancestor of the imported VDPV2 could date back 2.6 years (95% HPD: 1.7-3.7) in Senegal. We suggest that all VDPV2s circulating in 2020-21 in Senegal, Guinea, Gambia, and Mauritania have an ancestral origin in Senegal estimated around 2015. All 50 stool samples from healthy case contacts collected in Spain (n = 25) and Senegal (n = 25) and four wastewater samples collected in Spain were poliovirus negative. Discussion: By using a whole-genome sequencing protocol with unbiased metagenomics from the clinical sample and viral isolate with high sequence coverage, efficiency, and throughput, we confirmed the classification of VDPV as a circulating type. The close genomic linkage with strains from Senegal was consistent with their classification as imported. Given the scarce number of complete genome sequences for NPEV-C in public databases, this protocol could help expand poliovirus and NPEV-C sequencing capacity worldwide.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

Introduction: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. Methods: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. Results: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. Conclusion: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Introducción: El 14 de marzo de 2020 España declaró el estado de alarma por la pandemia por COVID-19 incluyendo medidas de confinamiento. El objetivo es describir el proceso de desescalada de estas medidas. Métodos: Un plan de transición hacia una nueva normalidad, del 28 de abril, incluía 4 fases secuenciales incrementando progresivamente las actividades socioeconómicas y la movilidad. Concomitantemente, se implementó una nueva estrategia de diagnóstico precoz, vigilancia y control. Se estableció un mecanismo de decisión bilateral entre Gobierno central y comunidades autónomas (CCAA), guiado por un panel de indicadores cualitativos y cuantitativos de la situación epidemiológica y las capacidades básicas. Las unidades territoriales evaluadas comprendían desde zonas básicas de salud hasta CCAA. Resultados: El proceso se extendió del 4 de mayo al 21 de junio y se asoció a planes de refuerzo de las capacidades en las CCAA. La incidencia disminuyó de una mediana inicial de 7,4 por 100.000 en 7 días a 2,5 al final del proceso. La mediana de pruebas PCR aumentó del 53% al 89% de los casos sospechosos, y la capacidad total de 4,5 a 9,8 pruebas semanales por 1.000 habitantes; la positividad disminuyó del 3,5% al 1,8%. La mediana de casos con contactos trazados aumentó del 82% al 100%. Conclusión: La recogida y análisis sistemático de información y el diálogo interterritorial logaron un adecuado control del proceso. La situación epidemiológica mejoró, pero sobre todo, se aumentaron las capacidades, en todo el país y con criterios comunes, cuyo mantenimiento y refuerzo fue clave en olas sucesivas.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

INTRODUCTION: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. METHODS: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. RESULTS: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. CONCLUSION: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

[COVID-19 exposure setting, social and gender determinants in a mediterranean region.] / Características sociales y de género en el ámbito de contagio de COVID-19 en una región mediterránea.

OBJECTIVE: Knowledge of social and gender determinants, which influence the places where people are exposed to COVID-19, may be relevant in the development of preventive and control strategies. The aim of this paper was to determine the context in which COVID-19 cases were infected (household, work/labor, health, social-health, and social-leisure settings) according to country of origin, occupational social class and gender, which is essential in order to designing public health strategies. METHODS: A cross-sectional study of an epidemiological registry of 56,628 COVID-19 incident cases was made, whose exposure/contagion setting was studied according to the previous variables from June 15 to December 23, 2020, in the Region of Murcia (Spain). An exact Fisher test was used to study the distribution of COVID-19 cases based on the above variables. RESULTS: The cumulative incidence was higher in people from Africa (5,133.5 cases/100,000 inhabitants) and Latin America (11,351.1) than in non-immigrants (3,145.7). It was also higher in women (3,885.6) than in men (3,572.6). It is noteworthy, that 53.3% of the cases with employment were workers in industry or construction, artisans, agricultural workers, or elementary occupations. In contrast, during the second semester of 2020, 41.3% of the employed population in the Region of Murcia performed such jobs. The household was the main exposure setting (56.5% of cases with a known setting), followed by social-leisure (20.7%) and work/labor (18.2%). The labor settings were more important in immigrants from Africa (28.4%) and Latin America (35.7%) than in non-immigrants (12%), inversely to social-leisure settings. Labor context was more important in women (19.6%) than in men (16.5%) and in manual workers (44.1%) than in non-manual workers (26.6%). CONCLUSIONS: The context in which COVID-19 cases were infected is different according to social inequalities related to country of origin, gender and occupational social class.

OBJETIVO: El conocimiento de los determinantes sociales y de género que influyen en el ámbito de exposición al SARS-CoV-2 puede ser relevante en el planteamiento de estrategias preventivas y de control de la transmisión. No se han encontrado estudios previos que evalúen cómo influyen la clase social ocupacional y el país de origen en el ámbito de exposición del SARS-CoV-2. El objetivo de este trabajo fue conocer el contexto en que se contagiaron los casos de COVID-19 (ámbito: hogar, trabajo, sanitario, sociosanitario y social-ocio) según país de origen, clase social ocupacional y género, lo cual es esencial para orientar estrategias de Salud Pública. METODOS: Se realizó un estudio descriptivo de un registro epidemiológico de 56.628 casos incidentes de COVID-19 en los que se estudió el ámbito de exposición/contagio en función de las variables anteriormente indicadas entre el 15 de junio y el 23 de diciembre de 2020 en la Región de Murcia. Se utilizó una prueba exacta de Fisher para el estudio de la distribución de los casos de COVID-19 en función de las variables anteriores. RESULTADOS: La incidencia acumulada fue mayor en personas procedentes de África (5.133,5 casos por cada 100.000 habitantes) y Latinoamérica (11.351,1) que en no inmigrantes (3.145,7) y superior en mujeres (3.885,6) que en hombres (3.572,6). Es destacable que el 53,3% de los casos COVID-19 con empleo registrado eran operarios en industria o construcción, artesanos, trabajadores agrarios o con ocupaciones elementales (15 de junio y el 23 de diciembre de 2020). En contraste, el 41,3% de la población ocupada en la Región de Murcia realizaba dichos empleos (promedio 3º y 4º trimestre de 2020). El hogar fue el principal ámbito de contagio (56,5% de los casos con ámbito conocido), seguido del social-ocio (20,7%) y el laboral (18,2%). Este último tuvo mayor peso en personas procedentes de África (28,4%) y Latinoamérica (35,7%) que en no inmigrantes (12%), a la inversa que el social-ocio. Fue más importante en mujeres (19,6%) que en hombres (16,5%) y en trabajadores manuales (44,1%) que en no manuales (26,6%). CONCLUSIONES: El contexto en el que los casos de COVID-19 se contagiaron es diferente en función de las desigualdades sociales relativas a país de origen, género y clase social ocupacional.

Epidemiologic Features and Control Measures during Monkeypox Outbreak, Spain, June 2022.

During June 2022, Spain was one of the countries most affected worldwide by a multicountry monkeypox outbreak with chains of transmission without identified links to disease-endemic countries. We provide epidemiologic features of cases reported in Spain and the coordinated measures taken to respond to this outbreak.

Circulating Isovalerylcarnitine and Lung Cancer Risk: Evidence from Mendelian Randomization and Prediagnostic Blood Measurements.

BACKGROUND: Tobacco exposure causes 8 of 10 lung cancers, and identifying additional risk factors is challenging due to confounding introduced by smoking in traditional observational studies. MATERIALS AND METHODS: We used Mendelian randomization (MR) to screen 207 metabolites for their role in lung cancer predisposition using independent genome-wide association studies (GWAS) of blood metabolite levels (n = 7,824) and lung cancer risk (n = 29,266 cases/56,450 controls). A nested case-control study (656 cases and 1,296 matched controls) was subsequently performed using prediagnostic blood samples to validate MR association with lung cancer incidence data from population-based cohorts (EPIC and NSHDS). RESULTS: An MR-based scan of 207 circulating metabolites for lung cancer risk identified that blood isovalerylcarnitine (IVC) was associated with a decreased odds of lung cancer after accounting for multiple testing (log10-OR = 0.43; 95% CI, 0.29-0.63). Molar measurement of IVC in prediagnostic blood found similar results (log10-OR = 0.39; 95% CI, 0.21-0.72). Results were consistent across lung cancer subtypes. CONCLUSIONS: Independent lines of evidence support an inverse association of elevated circulating IVC with lung cancer risk through a novel methodologic approach that integrates genetic and traditional epidemiology to efficiently identify novel cancer biomarkers. IMPACT: Our results find compelling evidence in favor of a protective role for a circulating metabolite, IVC, in lung cancer etiology. From the treatment of a Mendelian disease, isovaleric acidemia, we know that circulating IVC is modifiable through a restricted protein diet or glycine and L-carnatine supplementation. IVC may represent a modifiable and inversely associated biomarker for lung cancer.

Olive oil consumption is associated with a lower risk of cardiovascular disease and stroke.

BACKGROUND & AIMS: The specific association of olive oil consumption with coronary heart disease (CHD) or stroke has not been totally established. OBJECTIVE: to examine whether olive oil consumption is associated with subclinical atherosclerosis, the risk of total cardiovascular disease (CVD), CHD, and stroke. METHODS: Three cohorts were included: AWHS (2318 men), SUN Project (18,266 men and women), and EPIC-Spain (39,393 men and women). Olive oil consumption was measured at baseline using validated questionnaires. RESULTS: In the AWHS, 747 participants had a positive coronary artery calcium score (CACS>0), and the OR (95% CI) was 0.89 (0.72, 1.10) in those with virgin olive oil consumption ≥30 g/day (v. <10 g/day). In the SUN Project (follow-up 10.8 years) 261 total CVD cases occurred, and the HR was 0.57 (0.34, 0.96) for consumptions ≥30 g/day (v. <10 g/day). In the EPIC-Spain (follow-up 22.8 years) 1300 CHD cases and 938 stroke cases occurred; the HRs for stroke according, 0 to <10 (ref), 10 to <20, 20 to <30, and ≥30 g/day of olive oil consumption, were 0.84 (0.70, 1.02), 0.80 (0.66, 0.96), 0.89 (0.74, 1.07). A weaker association was observed for CHD. The association was stronger among those consuming virgin olive oil, instead of common (refined). CONCLUSIONS: Olive oil is associated with lower risk of CVD and stroke. The maximum benefit could be obtained with a consumption between 20 and 30 g/day. The association could be stronger for virgin olive oil and might operate from the early stages of the disease.

An imported case of vaccine-derived poliovirus type 2, Spain in the context of the ongoing polio Public Health Emergency of International Concern, September 2021.

The monthly retrospective search for unreported acute flaccid paralysis (AFP) cases conducted as a complementary component of the Spanish AFP surveillance system identified a case of AFP in a child admitted in Spain from Senegal during August 2021. Vaccine-derived poliovirus 2 was identified in the stool in September 2021. We present public health implications and response undertaken within the framework of the National Action Plan for Polio Eradication and the Public Health Emergency of International Concern.

Dietary Methyl-Group Donor Intake and Breast Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

(1) Background: Methyl-group donors (MGDs), including folate, choline, betaine, and methionine, may influence breast cancer (BC) risk through their role in one-carbon metabolism; (2) Methods: We studied the relationship between dietary intakes of MGDs and BC risk, adopting data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort; (3) Results: 318,686 pre- and postmenopausal women were followed between enrolment in 1992-2000 and December 2013-December 2015. Dietary MGD intakes were estimated at baseline through food-frequency questionnaires. Multivariable Cox proportional hazards regression models were used to quantify the association between dietary intake of MGDs, measured both as a calculated score based on their sum and individually, and BC risk. Subgroup analyses were performed by hormone receptor status, menopausal status, and level of alcohol intake. During a mean follow-up time of 14.1 years, 13,320 women with malignant BC were identified. No associations were found between dietary intakes of the MGD score or individual MGDs and BC risk. However, a potential U-shaped relationship was observed between dietary folate intake and overall BC risk, suggesting an inverse association for intakes up to 350 µg/day compared to a reference intake of 205 µg/day. No statistically significant differences in the associations were observed by hormone receptor status, menopausal status, or level of alcohol intake; (4) Conclusions: There was no strong evidence for an association between MGDs involved in one-carbon metabolism and BC risk. However, a potential U-shaped trend was suggested for dietary folate intake and BC risk. Further research is needed to clarify this association.

Dietary intake of advanced glycation endproducts and risk of hepatobiliary cancers: A multinational cohort study.

Advanced glycation endproducts (AGEs) may contribute to liver carcinogenesis because of their proinflammatory and prooxidative properties. Diet is a major source of AGEs, but there is sparse human evidence on the role of AGEs intake in liver cancer etiology. We examined the association between dietary AGEs and the risk of hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition prospective cohort (n = 450 111). Dietary intake of three AGEs, Nε -[carboxymethyl]lysine (CML), Nε -[1-carboxyethyl]lysine (CEL) and Nδ -[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), was estimated using country-specific dietary questionnaires linked to an AGEs database. Cause-specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations between dietary AGEs and risk of hepatocellular carcinoma (HCC), gallbladder and biliary tract cancers were estimated using multivariable Cox proportional hazard regression. After a median follow-up time of 14.9 years, 255 cases of HCC, 100 cases of gallbladder cancer and 173 biliary tract cancers were ascertained. Higher intakes of dietary AGEs were inversely associated with the risk of HCC (per 1 SD increment, HR-CML  = 0.87, 95% CI: 0.76-0.99, HR-CEL  = 0.84, 95% CI: 0.74-0.96 and HR-MH-G1  = 0.84, 95% CI: 0.74-0.97). In contrast, positive associations were observed with risk of gallbladder cancer (per 1 SD, HR-CML  = 1.28, 95% CI: 1.05-1.56, HR-CEL  = 1.17; 95% CI: 0.96-1.40, HR-MH-G1  = 1.27, 95% CI: 1.06-1.54). No associations were observed for cancers of the intra and extrahepatic bile ducts. Our findings suggest that higher intakes of dietary AGEs are inversely associated with the risk of HCC and positively associated with the risk of gallbladder cancer.

Ultra-rare sarcomas: A consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities.

BACKGROUND: Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies. METHODS: The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra-rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra-rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical-pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan. RESULTS: It was agreed that the best criterion for a definition of ultra-rare sarcomas would be incidence. Ultra-rare sarcomas were defined as those with an incidence of approximately ≤1 per 1,000,000, to include those entities whose rarity renders them extremely difficult to conduct well powered, prospective clinical studies. On the basis of this threshold, a list of ultra-rare sarcomas was defined, which comprised 56 soft tissue sarcoma types and 21 bone sarcoma types. CONCLUSIONS: Altogether, the incidence of ultra-rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas. This confirms that the challenges inherent in ultra-rare sarcomas affect large numbers of patients.

Coffee consumption and colorectal cancer risk: a multicentre case-control study from Italy and Spain.

BACKGROUND: Coffee contains many bioactive substances that can play a role on colorectal cancer. Epidemiological evidence of coffee intake and colorectal cancer is, however, inconsistent. AIM: To provide further information on the risk of colorectal cancer in relation to coffee consumption. METHODS: Data derive from two companion case-control studies conducted in Italy and Spain within the European Union Project on Health Impacts of long-term exposure to disinfection by-products in Drinking Water and the Spanish Multi-Case Control study on Cancer. These included a total of 2289 incident cases with colorectal cancer and 3995 controls with information on coffee intake. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were derived from unconditional logistic regression models, adjusted for study centre, sex, age, education, smoking, and other covariates. RESULTS: Compared with never coffee drinkers, the OR was 0.99 (95% CI 0.95-1.02) for total coffee consumption. There was no significant trend in risk with dose or duration, the ORs being 0.95 (95% CI 0.72-1.25) for an amount of five or more cups per day of coffee and 0.95 (95% CI 0.75-1.19) for a duration of consumption of 50 years or longer. The OR was 1.04 (95% CI 0.87-1.25) for two or more cups per day of decaffeinated coffee. There were no heterogeneity across strata of various covariates, as well as no apparent differences between various anatomical subsites. CONCLUSION: This large pooled analysis of two studies shows no association of coffee and decaffeinated coffee with colorectal cancer risk.

Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer: A pooled analysis of data from two prospective cohort studies.

Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.

Kaposi sarcoma incidence, survival and trends: Data from the information network on rare cancers in Europe (RARECAREnet).

BACKGROUND: This study provides updated information on Kaposi sarcoma (KS) in Europe during 1995-2007 from the RARECARENet project. METHODS: Data comes from 59 population-based cancer registries in 22 countries. KS was defined as ICD-O-3 morphology code 9140 combined with any topography code. Crude and age-adjusted incidence rates and relative survival for years of diagnosis 2000-2007 and with trends during 1995-2007 were calculated overall, by age and by country. RESULTS: The crude annual incidence rate was 0.28 per 100,000 and age-adjusted incidence was 0.23 per 100,000; incidence increased with age, from 0.18/100,000 at age 0-44 to 0.25/100,000 at age 45-64 and 0.69/100,000 at age 65 and over. Age-adjusted incidence in males was more than four times that in females. Portugal, which had the highest incidence of AIDS in Europe, had by far the highest incidence of KS at age 0-44, 1.44/100,000, more than four times the rate in any other country. Incidence among males in Europe aged 0-44 fell significantly between 1995-1998 and 1999-2002, followed by a significant increase in 2003-2007. Younger patients, with predominantly AIDS-related KS, formerly had a worse prognosis, but since 1999-2001 5-year relative survival increased for patients aged under 65, and by 2005-2007 was 83-86 % for all three age groups 0-44, 45-64, and 65 and over. CONCLUSION: Survival and quality of life for the increasing number of people in Europe affected by KS should improve further following the development of evidence-based guidelines for its management. Population-based cancer registries will continue to play a vital role in monitoring the burden of KS and improvements in its outcome.

Interaction Between GAD65 Antibodies and Dietary Fish Intake or Plasma Phospholipid n-3 Polyunsaturated Fatty Acids on Incident Adult-Onset Diabetes: The EPIC-InterAct Study.

OBJECTIVE: Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes. RESEARCH DESIGN AND METHODS: We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed. RESULTS: The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative (P = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs. CONCLUSIONS: High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.

Rare thyroid malignancies in Europe: Data from the information network on rare cancers in Europe (RARECAREnet).

OBJECTIVE: Limited information is available on the incidence of rare thyroid cancer (TC) subtypes: anaplastic (ATC) and medullary (MTC). The aim of this study was to describe incidence variations and trends across European countries of all TC subtypes. MATERIALS AND METHODS: We used the RARECAREnet database including 80721 TC incident cases in the period 2000-2007 from 77 population-based cancer registries (CRs) in Europe. In the trend analyses, we included 68890 TC cases from 53 CRs with at least 6 years of incidence data in the years 2000-2007. RESULTS: In Europe age-standardised incidence rates (ASR) in women were <0.3/100,000 for MTC and ATC whereas ASR were 5.3/100,000 for papillary thyroid cancer (PTC) and 1.1/100,000 for follicular TC (FTC). Corresponding ASRs in men were <0.2/100,000 for MTC and ATC, 1.5 for PTC and 0.4 for FTC. Across countries and in both sexes the incidence of FTC and MTC was moderately correlated (r ~ 0.5) with that of PTC, while a less marked correlation (r < 0.4) emerged for ATC ASRs. The changes of the PTC ASRs across countries and time were weakly (r < 0.3) or moderately (r ~ 0.5) correlated to the changes of the other subtypes for both sexes. CONCLUSION: The huge increase and heterogeneity between countries of PTC incidence has a small influence on the trends and variations of MTC and ATC in Europe. Large-scale epidemiological and clinical registry-based studies are warranted to increase knowledge about the rarest TC subtypes. This information would be fundamental for the design of new clinical trials and for inference.

Validation of self-reported perception of proximity to industrial facilities: MCC-Spain study.

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.

Healthy lifestyle and the risk of pancreatic cancer in the EPIC study.

Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants' shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e-09) and 0.77 (0.72, 0.82; ptrend = 1.7e-15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e-04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.