Consumption of aspartame and other artificial sweeteners and risk of cancer in the Spanish multicase-control study (MCC-Spain).

Use of artificial sweeteners (AS) such as aspartame, cyclamate, saccharin and sucralose is widespread. We evaluated the association of use of aspartame and other AS with cancer. In total 1881 colorectal, 1510 breast, 972 prostate and 351 stomach cancer and 109 chronic lymphocytic leukaemia (CLL) cases and 3629 population controls from the Spanish Multicase-Control (MCC-Spain) study were recruited (2008-2013). The consumption of AS, from table-top sweeteners and artificially sweetened beverages, was assessed through a self-administered and validated food frequency questionnaire (FFQ). Sex-specific quartiles among controls were determined to compare moderate consumers (

Validity of type 2 diabetes diagnosis in a population-based electronic health record database.

BACKGROUND: The increasing burden of type 2 diabetes mellitus makes the continuous surveillance of its prevalence and incidence advisable. Electronic health records (EHRs) have great potential for research and surveillance purposes; however the quality of their data must first be evaluated for fitness for use. The aim of this study was to assess the validity of type 2 diabetes diagnosis in a primary care EHR database covering more than half a million inhabitants, 97% of the population in Navarra, Spain. METHODS: In the Navarra EPIC-InterAct study, the validity of the T90 code from the International Classification of Primary Care, Second Edition was studied in a primary care EHR database to identify incident cases of type 2 diabetes, using a multi-source approach as the gold standard. The sensitivity, specificity, positive predictive value, negative predictive value and the kappa index were calculated. Additionally, type 2 diabetes prevalence from the EHR database was compared with estimations from a health survey. RESULTS: The sensitivity, specificity, positive predictive value and negative predictive value of incident type 2 diabetes recorded in the EHRs were 98.2, 99.3, 92.2 and 99.8%, respectively, and the kappa index was 0.946. Overall prevalence of type 2 diabetes diagnosed in the EHRs among adults (35-84 years of age) was 7.2% (95% confidence interval [CI] 7.2-7.3) in men and 5.9% (95% CI 5.8-5.9) in women, which was similar to the prevalence estimated from the health survey: 8.5% (95% CI 7.1-9.8) and 5.5% (95% CI 4.4-6.6) in men and women, respectively. CONCLUSIONS: The high sensitivity and specificity of type 2 diabetes diagnosis found in the primary care EHRs make this database a good source for population-based surveillance of incident and prevalent type 2 diabetes, as well as for monitoring quality of care and health outcomes in diabetic patients.

Colorectal cancer risk and nitrate exposure through drinking water and diet.

Ingested nitrate leads to the endogenous synthesis of N-nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated with nitrate exposure in drinking water and diet. A case-control study in Spain and Italy during 2008-2013 was conducted. Hospital-based incident cases and population-based (Spain) or hospital-based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long-term waterborne ingested nitrate was derived from routine monitoring records, linked to subjects' residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors and other covariables. Generalized additive models (GAMs) were used to analyze exposure-response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. In total 1,869 cases and 3,530 controls were analyzed. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 versus ≤5 mg/day, overall. Associations were larger among men versus women, and among subjects with high red meat intake. GAMs showed increasing exposure-response relationship among men. Animal-derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research.

Risk of type 2 diabetes according to traditional and emerging anthropometric indices in Spain, a Mediterranean country with high prevalence of obesity: results from a large-scale prospective cohort study.

BACKGROUND: Obesity is a major risk factor for type 2 diabetes mellitus (T2DM). A proper anthropometric characterisation of T2DM risk is essential for disease prevention and clinical risk assessement. METHODS: Longitudinal study in 37 733 participants (63% women) of the Spanish EPIC (European Prospective Investigation into Cancer and Nutrition) cohort without prevalent diabetes. Detailed questionnaire information was collected at baseline and anthropometric data gathered following standard procedures. A total of 2513 verified incident T2DM cases occurred after 12.1 years of mean follow-up. Multivariable Cox regression was used to calculate hazard ratios of T2DM by levels of anthropometric variables. RESULTS: Overall and central obesity were independently associated with T2DM risk. BMI showed the strongest association with T2DM in men whereas waist-related indices were stronger independent predictors in women. Waist-to-height ratio revealed the largest area under the ROC curve in men and women, with optimal cut-offs at 0.60 and 0.58, respectively. The most discriminative waist circumference (WC) cut-off values were 99.4 cm in men and 90.4 cm in women. Absolute risk of T2DM was higher in men than women for any combination of age, BMI and WC categories, and remained low in normal-waist women. The population risk of T2DM attributable to obesity was 17% in men and 31% in women. CONCLUSIONS: Diabetes risk was associated with higher overall and central obesity indices even at normal BMI and WC values. The measurement of waist circumference in the clinical setting is strongly recommended for the evaluation of future T2DM risk in women.

[Survival of cancer patients in Navarre and comparison with Spain].

BACKGROUND: To analyze the survival of adult cancer patients in Navarre, describe its trend, and compare the data for this Spanish Autonomous Community against that reported for Spain. METHODS: Records of adult cancer patients were retrieved from the Navarre´s population-based cancer registry for two periods (1999-2007 and 2008-2016). The vital status had been updated to 2020. Observed survival, net survival and age-standardized net survival at five years with 95% confidence intervals were estimated overall and for twenty-nine cancer groups. RESULTS: We analyzed 57,564 cases. Age-standardized net survival was 59.9% (59.1-60.8) and 63.8% (62.8-64.7) for males and females diagnosed with cancer during the 2008-2016 period, respectively. Age-standardized net survival ranged from 13.4% (10.4-17.4) for pancreatic cancer to 94.0% (88.1-100) for thyroid cancer in male patients, and from 11.9% (7.2-19.7) for liver cancer to 95.6% (92.6-98.6-%) for thyroid cancer in female patients. Compared with cases diagnosed in the 1999-2007 period, age-standardized net survival increased in 10 cancer groups, resulting in an overall increase of 5.1 (4.1-6.0) percentage points. The age-standardized net survival in Navarre was 2.7 (1.9-3.4) percentage points higher than that described for Spain for the 2008-2013 period. CONCLUSIONS: In Navarre, the survival of cancer patients diagnosed during the 2008-2016 period improved significantly in comparison to the 1999-2007 period. Different factors may explain this improvement, including earlier diagnoses, more effective treatment options, and better healthcare processes. Overall, survival was higher in women than in men. Our results suggest a higher survival rate in Navarre than in Spain.

Circulating miRNAs signature on breast cancer: the MCC-Spain project.

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.

Use of medical care during pandemic (H1N1) 2009, Navarre, Spain.

Of 233 households with laboratory-confirmed pandemic (H1N1) 2009 in Navarre, Spain, only 64% (107/166) of contacts with influenza-like illness had sought medical care. This value was lower for adults (53%, 39/74) than for children <15 years of age (74%, 68/92), as well as for those with cases secondary to another household case (58%, 64/111).

Supervivencia de los pacientes con cáncer en Navarra y comparación con España / Survival of cancer patients in Navarre and comparison with Spain

Fundamento: Analizar la supervivencia de pacientes adultosdiagnosticados de cáncer en Navarra, describir su tendencia ycompararla con la supervivencia en España. Métodos: Los casos de personas adultas diagnosticadas decáncer en los periodos 1999-2007 y 2008-2016 fueron seleccionados del registro poblacional de cáncer de Navarra; su esta-do vital se había actualizado hasta 2020. La supervivencia observada, la supervivencia neta (SN) y la SN estandarizada poredad (SNe) a cinco años, junto con sus intervalos de confianzaal 95%, fueron estimados globalmente y para veintinueve grupos de cáncer. Resultados. Se analizaron 57.564 casos. La SNe de los hombresy mujeres diagnosticados en 2008-2016 fue 59,9% (59,1-60,8) y63,8% (62,8-64,7), respectivamente. En hombres varió desde13,4% (10,4-17,4) en cáncer de páncreas hasta 94,0% (88,1-100) en el de tiroides, y en mujeres desde 11,9% (7,2-19,7) enel cáncer de hígado hasta 95,6% (92,6-98,6) en el de tiroides. Encomparación con los casos diagnosticados en 1999-2007, la SNeaumentó en diez grupos de cáncer, resultando un incrementoglobal de 5,1 (4,1-6,0) puntos porcentuales. La SNe en Navarrafue 2,7 (1,9-3,4) puntos porcentuales mayor que la descrita enEspaña en 2008-2013. Conclusiones: En Navarra la supervivencia de pacientes diagnosticados de cáncer en el periodo 2008-2016 mejoró significativamente respecto al periodo 1999-2007. Esta mejora obedece probablemente a múltiples factores, incluyendo diagnósticos mástempranos, opciones terapéuticas más efectivas y mejora delproceso asistencial. La supervivencia global fue mayor en las mujeres que en los hombres. Además, los resultados sugieren unasupervivencia más alta en Navarra en comparación con España.(AU)

Background: To analyze the survival of adult cancer patients inNavarre, describe its trend, and compare the data for this Spanish Autonomous Community against that reported for Spain. Methods: Records of adult cancer patients were retrieved fromthe Navarre’s population-based cancer registry for two periods(1999-2007 and 2008-2016). The vital status had been updated to2020. Observed survival, net survival and age-standardized netsurvival at five years with 95% confidence intervals were estimated overall and for twenty-nine cancer groups. Results: We analyzed 57,564 cases. Age-standardized net survival was 59.9% (59.1-60.8) and 63.8% (62.8-64.7) for males and females diagnosed with cancer during the 2008-2016 period,respectively. Age-standardized net survival ranged from 13.4%(10.4-17.4) for pancreatic cancer to 94.0% (88.1-100) for thyroidcancer in male patients, and from 11.9% (7.2-19.7) for livercancer to 95.6% (92.6-98.6-%) for thyroid cancer in female patients. Compared with cases diagnosed in the 1999-2007 period,age-standardized net survival increased in 10 cancer groups, resulting in an overall increase of 5.1 (4.1-6.0) percentage points.The age-standardized net survival in Navarre was 2.7 (1.9-3.4)percentage points higher than that described for Spain for the2008-2013 period. Conclusions: In Navarre, the survival of cancer patients diagnosed during the 2008-2016 period improved significantlyin comparison to the 1999-2007 period. Different factors mayexplain this improvement, including earlier diagnoses, moreeffective treatment options, and better healthcare processes.Overall, survival was higher in women than in men. Our resultssuggest a higher survival rate in Navarre than in Spain.(AU)

Long-term exposure to trihalomethanes in drinking water and breast cancer in the Spanish multicase-control study on cancer (MCC-SPAIN).

BACKGROUND: Exposure to trihalomethanes (THMs) in drinking water has consistently been associated with an increased risk of bladder cancer, but evidence on other cancers including the breast is very limited. OBJECTIVES: We assessed long-term exposure to THMs to evaluate the association with female breast cancer (BC) risk. METHODS: A multi case-control study was conducted in Spain from 2008 to 2013. We included 1003 incident BC cases (women 20-85years old) recruited from 14 hospitals and 1458 population controls. Subjects were interviewed to ascertain residential histories and major recognized risk factors for BC. Mean residential levels of chloroform, brominated THMs (Br-THMs) and the sum of both as total THM (TTHMs) during the adult-lifetime were calculated. RESULTS: Mean adult-lifetime residential levels ranged from 0.8 to 145.7µg/L for TTHM (median=30.8), from 0.2 to 62.4µg/L for chloroform (median=19.7) and from 0.3 to 126.0µg/L for Br-THMs (median=9.7). Adult-lifetime residential chloroform was associated with BC (adjusted OR=1.47; 95%CI=1.05, 2.06 for the highest (>24µg/L) vs. lowest (<8µg/L) quartile; p-trend=0.024). No association was detected for residential Br-THMs (OR=0.91; 95%CI=0.68, 1.23 for >31µg/L vs. <6µg/L) or TTHMs (OR=1.14; 95%CI=0.83, 1.57 for >48µg/L vs. <22µg/L). CONCLUSIONS: At common levels in Europe, long-term residential total THMs were not related to female breast cancer. A moderate association with chloroform was suggested at the highest exposure category. This large epidemiological study with extensive exposure assessment overcomes several limitations of previous studies but further studies are needed to confirm these results.

Care patterns and changes in treatment for nonmetastatic breast cancer in 2013-2014 versus 2005: a population-based high-resolution study.

Studies on recent trends in patterns of care for breast cancer patients are scarce. This study aims to examine the patterns and trends in the treatment of women with nonmetastatic breast cancer according to major recommended treatment options. A population-based study was carried out in Navarra, Spain, including all women with a primary invasive nonmetastasized breast cancer, diagnosed in 2005 and in 2013-2014. We compared patients' characteristics and treatment patterns between periods. Factors associated with receipt of recommended treatment were examined by multivariate logistic regression. Of the 719 patients included, 90% received guideline-adherent locoregional treatment. Over the two periods, there was an increasing use of sentinel lymph node biopsy as opposed to axillary lymph node dissection as the first axillary procedure. Among women with oestrogen receptor-positive tumours, 96% received endocrine therapy. The proportion of high-risk patients who were treated with chemotherapy increased between the two periods from 65 to 74% (P=0.079) and, among patients with human epidermal growth factor receptor 2-positive tumours, the receipt of targeted treatment increased from 37 to 72% (P<0.001). The main factors associated independently with a lower probability of receiving recommended treatment were age 70 years or older for all treatment modalities and comorbidity for locoregional treatment and chemotherapy. The proportion of women with breast cancer who received treatment according to recent European guidelines in Navarra has increased from 2005 to 2013-2014, resulting in a high level of adherence to standard care. Most failures in adherence to these standards are related to older age or comorbidities.

Physical activity domains and risk of gastric adenocarcinoma in the MCC-Spain case-control study.

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

Household transmission of influenza A(H1N1)pdm09 in the pandemic and post-pandemic seasons.

BACKGROUND: The transmission of influenza viruses occurs person to person and is facilitated by contacts within enclosed environments such as households. The aim of this study was to evaluate secondary attack rates and factors associated with household transmission of laboratory-confirmed influenza A(H1N1)pdm09 in the pandemic and post-pandemic seasons. METHODS: During the 2009-2010 and 2010-2011 influenza seasons, 76 sentinel physicians in Navarra, Spain, took nasopharyngeal and pharyngeal swabs from patients diagnosed with influenza-like illness. A trained nurse telephoned households of those patients who were laboratory-confirmed for influenza A(H1N1)pdm09 to ask about the symptoms, risk factors and vaccination status of each household member. RESULTS: In the 405 households with a patient laboratory-confirmed for influenza A(H1N1)pdm09, 977 susceptible contacts were identified; 16% of them (95% CI 14-19%) presented influenza-like illness and were considered as secondary cases. The secondary attack rate was 14% in 2009-2010 and 19% in the 2010-2011 season (p=0.049), an increase that mainly affected persons with major chronic conditions. In the multivariate logistic regression analysis, the risk of being a secondary case was higher in the 2010-2011 season than in the 2009-2010 season (adjusted odds ratio: 1.72; 95% CI 1.17-2.54), and in children under 5 years, with a decreasing risk in older contacts. Influenza vaccination was associated with lesser incidence of influenza-like illness near to statistical significance (adjusted odds ratio: 0.29; 95% CI 0.08-1.03). CONCLUSION: The secondary attack rate in households was higher in the second season than in the first pandemic season. Children had a greater risk of infection. Preventive measures should be maintained in the second pandemic season, especially in high-risk persons.

[Factors associated with household transmission of influenza (H1N1) 2009]. / Factores asociados a la transmisión a los convivientes de gripe (H1N1) 2009.

BACKGROUND: A good part of the transmission of influenza occurs in the household context. The main objective of this study was to evaluate the factors associated with the index cases generating secondary cases in household. METHODS: We designed an observational, retrospective, multicenter through the implementation of a telephone survey in three regions of Spain. The study population were hospitalized and outpatient cases of confirmed H1N1 (2009) reported to the surveillance units from week 44 of 2009. We calculated the secondary attack rate within the household (TAI) and confidence interval of 95%. Factors associated with household transmission were analyzed by logistic regression, calculating odds ratios and confidence intervals at 95%. RESULTS: the secondary attack rate was 11.3% (95% CI 9.9 to 12.7) within the household. The number of household contacts was the main factor associated with the transmission (OR: 5,02 CI95% 1,78-14,13). CONCLUSION: The factor most associated with the generation of secondary cases is the family size, being greater the larger the group of cohabiting, which is consistent with the data provided by WHO.