Compliance with current dietary recommendations and geographical variability of diet in women participating in 7 screening programs for breast cancer in Spain

Introducción: Una dieta saludable es especialmente importante durante la menopausia, periodo en el que aumenta el riesgo de varios problemas de salud. Analizamos la dieta de mujeres peri y postmenopáusicas españolas y el grado de cumplimiento de las recomendaciones actuales. Material y métodos: Estudio transversal en 3.574 mujeres de 45-68 años que acuden al cribado de cáncer de mama en 7 centros (A Coruña, Barcelona, Burgos, Palma de Mallorca, Pamplona, Valencia y Zaragoza). Se recogió la dieta mediante un cuestionario de frecuencia de alimentos validado para población española. Para la valoración del cumplimiento de las recomendaciones actuales se utilizaron los rangos recomendados por la Sociedad Española de Nutrición Comunitaria para ingesta de grupos de alimentos y las Ingestas Diarias Recomendadas (IDR) para energía, vitaminas y minerales de la Federación Española de Nutrición, Alimentación y Dietética. Resultados: El 29% de las mujeres eran obesas y un 42% tenía sobrepeso. El aporte calórico medio fue de 2.053 kcal (DE: 480). El perfil calórico general fue de: 43% de la energía aportada por lo carbohidratos, 36% por las grasas, 20% por las proteínas. Se evidenció una ingesta deficiente de vitamina D en todos los nodos del estudio, con una ingesta media general de 2,14 μg/día. Se detectó a su vez una ingesta deficitaria de vitamina E en A Coruña y Burgos. Todos los centros presentaron una ingesta elevada de productos lácteos y de legumbres. El consumo de frutas y verduras fue muy heterogéneo siendo especialmente elevada su ingesta en Mallorca y Valencia mientras que fue baja para ambos grupos de alimentos en A Coruña. La ingesta de aceite de oliva fue elevada en todos los centros exceptuando Burgos con un 74,3% de las mujeres estudiadas por debajo de las 3 raciones al día recomendadas. Conclusiones: Una dieta con menos grasas y proteínas y más rica en vegetales, frutos secos y alimentos ricos en hidratos de carbono equilibraría el balance energético y mejoraría la calidad de la dieta corrigiendo las bajas ingestas de vitaminas D y E. Estas recomendaciones son especialmente importantes en las ciudades más alejadas de la costa mediterránea donde se han detectado mayores incumplimientos de las recomendaciones vigentes y una dieta más alejada de la dieta mediterránea.Introduction: A healthy diet is especially important during menopause, a period which increases the risk of various health problems. We analyzed the diet of periand postmenopausal Spanish women and the degree of compliance with current recommendations. Material and methods: We studied 3574 women 45-68 years old who attended breast cancer screening programmes in 7 centres (A Coruña, Barcelona, Burgos, Palma de Mallorca, Pamplona, Valencia and Zaragoza). Diet information was collected using a food frequency questionnaire validated for the Spanish population. For the assessment of compliance with current guidelines we used the recommendations by the Spanish Society of Community Nutrition for food groups intake and by the Spanish Federation of Nutrition, Food and Dietetics for energy, vitamins and minerals intake. Results: The 29% of women were obese and 42% overweight. The average caloric intake was 2.053 kcal (SD 480). The general energy profile was: 43% of the energy from the carbohydrates, 36% from fats, and 20% from proteins. There was a low vitamin D intake in all centres of the study, with an overall mean intake of 2.14 mg/day. A deficit of vitamin E intake in A Coruña and Burgos was also detected. Intake of dairy products and vegetables was high in all the study centers. The consumption of fruits and vegetables was very heterogeneous, with high intakes observed in Mallorca and Valencia and low for both food groups in A Coruña. The olive oil intake was high in all centers except Burgos with 74.3% of the women studied below the recommended 3 servings per day. Conclusions: A diet with less fat and protein and a higher consumption of vegetables, nuts and foods rich in carbohydrate might balance the energy intake and improve the quality of the diet correcting the low intakes of vitamins D and E. These recommendations are especially important in cities far from the Mediterranean coast where more breaches have been detected over the current recommendations with a lower adherence to the Mediterranean diet.Este estudio ha recibido financiación del Fondo de Investigación Sanitaria (proyecto PI060386) y de Astra-Zéneca (convenio de colaboración entre Astra- Zeneca y el Instituto de salud Carlos III 1306-1306 EPY

BRCA1 and BRCA2 5′ noncoding region variants identified in breast cancer patients alter promoter activity and protein binding

© 2018 The Authors. Human Mutation published by Wiley Periodicals, Inc. The widespread use of next generation sequencing for clinical testing is detecting an escalating number of variants in noncoding regions of the genome. The clinical significance of the majority of these variants is currently unknown, which presents a significant clinical challenge. We have screened over 6,000 early-onset and/or familial breast cancer (BC) cases collected by the ENIGMA consortium for sequence variants in the 5′ noncoding regions of BC susceptibility genes BRCA1 and BRCA2, and identified 141 rare variants with global minor allele frequency \u3c 0.01, 76 of which have not been reported previously. Bioinformatic analysis identified a set of 21 variants most likely to impact transcriptional regulation, and luciferase reporter assays detected altered promoter activity for four of these variants. Electrophoretic mobility shift assays demonstrated that three of these altered the binding of proteins to the respective BRCA1 or BRCA2 promoter regions, including NFYA binding to BRCA1:c.-287C\u3eT and PAX5 binding to BRCA2:c.-296C\u3eT. Clinical classification of variants affecting promoter activity, using existing prediction models, found no evidence to suggest that these variants confer a high risk of disease. Further studies are required to determine if such variation may be associated with a moderate or low risk of BC

Compliance with current dietary recommendations and geographical variability of diet in women participating in 7 screening programs for breast cancer in Spain.

[ES] Introducción:Una dieta saludable es especialmenteimportante durante la menopausia, periodo en el queaumenta el riesgo de varios problemas de salud. Analiza-mos la dieta de mujeres peri y postmenopáusicas españo-las y el grado de cumplimiento de las recomendacionesactuales. Material y métodos:Estudio transversal en 3.574 muje-res de 45-68 años que acuden al cribado de cáncer demama en 7 centros (A Coruña, Barcelona, Burgos, Palmade Mallorca, Pamplona, Valencia y Zaragoza). Se recogióla dieta mediante un cuestionario de frecuencia de ali-mentos validado para población española. Para la valora-ción del cumplimiento de las recomendaciones actuales seutilizaron los rangos recomendados por la SociedadEspañola de Nutrición Comunitaria para ingesta de gru-pos de alimentos y las Ingestas Diarias Recomendadas(IDR) para energía, vitaminas y minerales de la Federa-ción Española de Nutrición, Alimentación y Dietética. Resultados:El 29% de las mujeres eran obesas y un42% tenía sobrepeso. El aporte calórico medio fue de2.053 kcal (DE: 480). El perfil calórico general fue de: 43% de la energía aportada por lo carbohidratos, 36%por las grasas, 20% por las proteínas. Se evidenció unaingesta deficiente de vitamina D en todos los nodos delestudio, con una ingesta media general de 2,14 μg/día. Sedetectó a su vez una ingesta deficitaria de vitamina E en ACoruña y Burgos. Todos los centros presentaron unaingesta elevada de productos lácteos y de legumbres. Elconsumo de frutas y verduras fue muy heterogéneosiendo especialmente elevada su ingesta en Mallorca yValencia mientras que fue baja para ambos grupos de ali-mentos en A Coruña. La ingesta de aceite de oliva fue ele-vada en todos los centros exceptuando Burgos con un74,3% de las mujeres estudiadas por debajo de las 3raciones al día recomendadas. Conclusiones:Una dieta con menos grasas y proteínasy más rica en vegetales, frutos secos y alimentos ricos enhidratos de carbono equilibraría el balance energético ymejoraría la calidad de la dieta corrigiendo las bajasingestas de vitaminas D y E. Estas recomendaciones sonespecialmente importantes en las ciudades más alejadasde la costa mediterránea donde se han detectado mayoresincumplimientos de las recomendaciones vigentes y unadieta más alejada de la dieta mediterránea. [EN] A healthy diet is especially important during menopause, a period which increases the risk of various health problems. We analyzed the diet of periand postmenopausal Spanish women and the degree of compliance with current recommendations. We studied 3574 women 45-68 years old who attended breast cancer screening programmes in 7 centres (A Coruña, Barcelona, Burgos, Palma de Mallorca, Pamplona, Valencia and Zaragoza). Diet information was collected using a food frequency questionnaire validated for the Spanish population. For the assessment of compliance with current guidelines we used the recommendations by the Spanish Society of Community Nutrition for food groups intake and by the Spanish Federation of Nutrition, Food and Dietetics for energy, vitamins and minerals intake. The 29% of women were obese and 42% overweight. The average caloric intake was 2.053 kcal (SD 480). The general energy profile was: 43% of the energy from the carbohydrates, 36% from fats, and 20% from proteins. There was a low vitamin D intake in all centres of the study, with an overall mean intake of 2.14 mg/day. A deficit of vitamin E intake in A Coruña and Burgos was also detected. Intake of dairy products and vegetables was high in all the study centers. The consumption of fruits and vegetables was very heterogeneous, with high intakes observed in Mallorca and Valencia and low for both food groups in A Coruña. The olive oil intake was high in all centers except Burgos with 74.3% of the women studied below the recommended 3 servings per day. A diet with less fat and protein and a higher consumption of vegetables, nuts and foods rich in carbohydrate might balance the energy intake and improve the quality of the diet correcting the low intakes of vitamins D and E. These recommendations are especially important in cities far from the Mediterranean coast where more breaches have been detected over the current recommendations with a lower adherence to the Mediterranean diet.Este estudio ha recibido financiación del Fondo deInvestigación Ssanitaria (proyecto PI060386) y de Astra-Zéneca (convenio de colaboración entre Astra-Zeneca y el Instituto de salud Carlos III 1306-1306EPY).S

A European study on alcohol and drug use among young drivers : The TEND by night study design and methodology

Background. Young individuals are the age group with the highest risk of car accidents. One of main explanations relies on the use of psychoactive substances (alcohol, illegal and medicinal drugs), which are known to be major risk factors of road accidents, and whose consumption is almost universally more common among younger drivers. Although the correlation between psychoactive substances use and decrease in driving performance has been established in controlled experimental or laboratory settings, few studies were conducted in naturalistic circumstances. The TEND by Night project has been designed to evaluate the relationship between driving performance and psychoactive substances assumption in young drivers enrolled at typical places of consumption. Methods/Design. The TEND by Night project, endorsed by the European Commission, is a multidisciplinary, multi-centric, cross-sectional study conducted in six European countries (Italy, Belgium/Netherlands, Bulgaria, Spain, Poland and Latvia). The study population consists of 5000 young drivers aged 16-34 years, attending recreational sites during weekend nights. The intervention is based on the portal survey technique and includes several steps at the entrance and exit of selected sites, including the administration of semi-structured questionnaires, breath alcohol test, several drug assumption test, and measurement of the reaction time using a driving simulator. The main outcome is the difference in reaction time between the entrance and exit of the recreation site, and its correlation with psychoactive substances use. As a secondary outcome it will be explored the relationship between reaction time difference and the amount of consumption of each substance. All analyses will be multivariate. Discussion. The project methodology should provide some relevant advantages over traditional survey systems. The main strengths of the study include the large and multicentric sample, the objective measurement of substance assumption (which is typically self-reported), the application of a portal survey technique and the simultaneous evaluation of several psychoactive substances.publishersversionPeer reviewe

The Spectrum of FANCM Protein Truncating Variants in European Breast Cancer Cases

Germline protein truncating variants (PTVs) in the FANCM gene have been associated with a 2–4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of FANCM PTVs in Europe have never been investigated. In the present study, we collected the data of 114 European female breast cancer cases with FANCM PTVs ascertained in 20 centers from 13 European countries. We identified 27 different FANCM PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a maximum frequency in Finland and a lower relative frequency in Southern Europe. On the contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique FANCM PTVs, 15 have not been previously reported. We provide here the initial spectrum of FANCM PTVs in European breast cancer cases

Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors