Differences in breast cancer-risk factors between screen-detected and non-screen-detected cases (MCC-Spain study).

PURPOSE: The variation in breast cancer (BC)-risk factor associations between screen-detected (SD) and non-screen-detected (NSD) tumors has been poorly studied, despite the interest of this aspect in risk assessment and prevention. This study analyzes the differences in breast cancer-risk factor associations according to detection method and tumor phenotype in Spanish women aged between 50 and 69. METHODS: We examined 900 BC cases and 896 controls aged between 50 and 69, recruited in the multicase-control MCC-Spain study. With regard to the cases, 460 were detected by screening mammography, whereas 144 were diagnosed by other means. By tumor phenotype, 591 were HR+, 153 were HER2+, and 58 were TN. Lifestyle, reproductive factors, family history of BC, and tumor characteristics were analyzed. Logistic regression models were used to compare cases vs. controls and SD vs. NSD cases. Multinomial regression models (controls used as a reference) were adjusted for case analysis according to phenotype and detection method. RESULTS: TN was associated with a lower risk of SD BC (OR 0.30 IC 0.10-0.89), as were intermediate (OR 0.18 IC 0.07-0.44) and advanced stages at diagnosis (OR 0.11 IC 0.03-0.34). Nulliparity in postmenopausal women and age at menopause were related to an increased risk of SD BC (OR 1.60 IC 1.08-2.36; OR 1.48 IC 1.09-2.00, respectively). Nulliparity in postmenopausal women was associated with a higher risk of HR+ (OR 1.66 IC 1.15-2.40). Age at menopause was related to a greater risk of HR+ (OR 1.60 IC 1.22-2.11) and HER2+ (OR 1.59 IC 1.03-2.45) tumors. CONCLUSION: Reproductive risk factors are associated with SD BC, as are HR+ tumors. Differences in BC-risk factor associations according to detection method may be related to prevailing phenotypes among categories.

A prospective evaluation of plasma polyphenol levels and colon cancer risk.

Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre-diagnostic plasma polyphenols and colon cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (qvalues ) was computed to control for multiple comparisons. All statistical tests were two-sided. After false discovery rate correction and in continuous log2 -transformed multivariable models, equol (odds ratio [OR] per log2 -value, 0.86, 95% confidence interval [95% CI] = 0.79-0.93; qvalue = 0.01) and homovanillic acid (OR per log2 -value, 1.46, 95% CI = 1.16-1.84; qvalue = 0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR = 0.61, 95% CI = 0.41-0.91, ptrend = 0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR = 1.72, 95% CI = 1.17-2.53, ptrend < 0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis.

Reproductive risk factors in breast cancer and genetic hormonal pathways: a gene-environment interaction in the MCC-Spain project.

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.

Meat intake, cooking methods and doneness and risk of colorectal tumours in the Spanish multicase-control study (MCC-Spain).

PURPOSE: Although there is convincing evidence that red and processed meat intake increases the risk of colorectal cancer (CRC), the potential role of meat cooking practices has not been established yet and could partly explain the current heterogeneity of results among studies. Therefore, we aimed to investigate the association between meat consumption and cooking practices and the risk of CRC in a population-based case-control study. METHODS: A total of 1671 CRC cases and 3095 controls recruited in Spain between September 2008 and December 2013 completing a food frequency questionnaire with a meat-specific module were included in the analyses. Odds ratios (OR) and confidence intervals (CI) were estimated by logistic regression models adjusted for known confounders. RESULTS: Total meat intake was associated with increased risk of CRC (OR T3-T1 1.41; 95% CI 1.19-1.67; p trend < 0.001), and similar associations were found for white, red and processed/cured/organ meat. Rare-cooked meat preference was associated with low risk of CRC in red meat (ORrare vs. medium 0.66; 95% CI 0.51-0.85) and total meat (ORrare vs. medium 0.56; 95% CI 0.37-0.86) consumers, these associations being stronger in women than in men. Griddle-grilled/barbecued meat was associated with an increased CRC risk (total meat: OR 1.45; 95% CI 1.13-1.87). Stewing (OR 1.25; 95% CI 1.04-1.51) and oven-baking (OR 1.18; 95% CI 1.00-1.40) were associated with increased CRC risk of white, but not red, meat. CONCLUSIONS: Our study supports an association of white, red, processed/cured/organ and total meat intake with an increased risk of CRC. Moreover, our study showed that cooking practices can modulate such risk.

Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study.

BACKGROUND: The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear. OBJECTIVE: To examine whether coffee consumption is associated with all-cause and cause-specific mortality. DESIGN: Prospective cohort study. SETTING: 10 European countries. PARTICIPANTS: 521 330 persons enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition). MEASUREMENTS: Hazard ratios (HRs) and 95% CIs estimated using multivariable Cox proportional hazards models. The association of coffee consumption with serum biomarkers of liver function, inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort (n = 14 800). RESULTS: During a mean follow-up of 16.4 years, 41 693 deaths occurred. Compared with nonconsumers, participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality (men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend < 0.001; women: HR, 0.93 [CI, 0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend < 0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend < 0.001). Among women, there was a statistically significant inverse association of coffee drinking with circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend < 0.001) and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend = 0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI, 1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher coffee consumption was associated with lower serum alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; γ-glutamyltransferase; and, in women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels. LIMITATIONS: Reverse causality may have biased the findings; however, results did not differ after exclusion of participants who died within 8 years of baseline. Coffee-drinking habits were assessed only once. CONCLUSION: Coffee drinking was associated with reduced risk for death from various causes. This relationship did not vary by country. PRIMARY FUNDING SOURCE: European Commission Directorate-General for Health and Consumers and International Agency for Research on Cancer.

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.

Association of Streptococcus gallolyticus subspecies gallolyticus with colorectal cancer: Serological evidence.

The colonic opportunist Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC). Large-scale seroepidemiological data for SGG antibodies and their possible association with CRC is currently missing. Associations between CRC and antibody responses to SGG were examined in 576 CRC cases and 576 controls matched by sex, age and province from a population-based multicase-control project (MCC-Spain). MCC-Spain was conducted between 2008 and 2013 in 12 Spanish provinces. Antibody responses to recombinant affinity-purified SGG pilus proteins Gallo1569, 2039, 2178 and 2179 were analysed by multiplex serology. Polyomavirus (PyV) JC VP1 and PyV 6 VP1 proteins served as disease-specificity controls. In the control population, antibody responses to pilus proteins were mostly weak. Antibody responses to individual pilus proteins Gallo2039 (OR: 1.58, 95% CI: 1.09-2.28), Gallo2178 (OR: 1.58, 95% CI: 1.09-2.30) and Gallo2179 (OR: 1.45, 95% CI: 1.00-2.11) were significantly associated with CRC risk. The association was stronger for positivity to two or more pilus proteins of Gallo1569, Gallo2178 and Gallo2179 (OR:1.93, 95% CI: 1.04-3.56) and for double-positivity to Gallo2178 and Gallo2179 (OR: 3.54, 95% CI: 1.49-8.44). The association between SGG infection and CRC risk was stronger among individuals younger than 65 years. For the first time we demonstrated a statistically significant association of exposure to SGG antigens and CRC in a large seroepidemiological study. These results should stimulate further studies on the role of SGG in CRC pathogenesis.

Modifiable causes of premature death in middle-age in Western Europe: results from the EPIC cohort study.

BACKGROUND: Life expectancy is increasing in Europe, yet a substantial proportion of adults still die prematurely before the age of 70 years. We sought to estimate the joint and relative contributions of tobacco smoking, hypertension, obesity, physical inactivity, alcohol and poor diet towards risk of premature death. METHODS: We analysed data from 264,906 European adults from the EPIC prospective cohort study, aged between 40 and 70 years at the time of recruitment. Flexible parametric survival models were used to model risk of death conditional on risk factors, and survival functions and attributable fractions (AF) for deaths prior to age 70 years were calculated based on the fitted models. RESULTS: We identified 11,930 deaths which occurred before the age of 70. The AF for premature mortality for smoking was 31 % (95 % confidence interval (CI), 31-32 %) and 14 % (95 % CI, 12-16 %) for poor diet. Important contributions were also observed for overweight and obesity measured by waist-hip ratio (10 %; 95 % CI, 8-12 %) and high blood pressure (9 %; 95 % CI, 7-11 %). AFs for physical inactivity and excessive alcohol intake were 7 % and 4 %, respectively. Collectively, the AF for all six risk factors was 57 % (95 % CI, 55-59 %), being 35 % (95 % CI, 32-37 %) among never smokers and 74 % (95 % CI, 73-75 %) among current smokers. CONCLUSIONS: While smoking remains the predominant risk factor for premature death in Europe, poor diet, overweight and obesity, hypertension, physical inactivity, and excessive alcohol consumption also contribute substantially. Any attempt to minimise premature deaths will ultimately require all six factors to be addressed.

Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Ecological Study in the Basque Country, Spain (2000-2011).

Chronic obstructive pulmonary disease (COPD) is a prevalent condition in adults aged ≥40 years characterized by progressive airflow limitation associated with chronic inflammatory response to noxious particles in the airways and lungs. Smoking, genetics, air pollution, nutrition and other factors may influence COPD development. Most hospitalizations and deaths for COPD are caused by its acute exacerbations, which greatly affect the health and quality of life of COPD patients and pose a high burden on health services. The aims of this project were to identify trends, geographic patterns and risk factors for COPD exacerbations, as revealed by hospitalizations and deaths, in the Basque Country, Spain, over a period of 12 years (2000-2011). Hospitalization and mortality rates for COPD were 262 and 18 per 100,000 population, respectively, with clusters around the biggest cities. Hospital mortality was 7.4%. Most hospitalized patients were male (77.4%) and accounted for 72.1% of hospital mortality. Hospitalizations decreased during the study period, except for 50-64 year-old women, peaking significantly. Using a multivariate modeling approach it was shown that hospitalizations were positively correlated with increased atmospheric concentrations of NO2, CO, PM10, and SO2, and increased influenza incidence, but were negatively associated with increased temperatures and atmospheric O3 concentration. COPD exacerbations decreased in the Basque Country during 2000-2011, but not among 50-64-year-old women, reflecting the high smoking prevalence among Spanish women during the 1970-1990s. The main metropolitan areas were those with the highest risk for COPD exacerbations, calling attention to the role of heavy car traffic. Influenza virus, cold temperatures, and increased atmospheric NO2, CO, PM10, and SO2 (but decreased O3) concentrations were identified as potential contributors to the burden of COPD exacerbations in the community. These findings are important for both the understanding of the disease process and in providing potential targets for COPD-reducing initiatives and new avenues for research.

Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992-1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99% confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p < 0.000) with fatty fish consumption and total mortality and with total fish consumption and cancer mortality (p = 0.046).

Development of a prediction model for fatal and non-fatal coronary heart disease and cardiovascular disease in patients with newly diagnosed type 2 diabetes mellitus: the Basque Country Prospective Complications and Mortality Study risk engine (BASCORE).

AIMS/HYPOTHESIS: The aim of this study was to construct a model for predicting CHD and cardiovascular disease (CVD) risk in patients with newly diagnosed type 2 diabetes in a southern European region. External validation of two other cardiovascular risk models and internal validation of our model were assessed. METHODS: We studied 65,651 people attending a primary care setting in the Basque Country Health Service. A 10-year prospective population-based cohort study was performed with 777 patients newly diagnosed with type 2 diabetes older than 24 years in a Sentinel Practice Network. Cardiovascular risk factors, CVD events and mortality were registered. Coefficients for the significant predictors of CHD and CVD were estimated using Cox models. We assessed the discrimination and calibration of the UK Prospective Diabetes Study risk engine (UKPDS-RE), the Framingham Risk Score-Regicor Study (FRS-RS) and the cardiovascular risk model we developed. RESULTS: The incidence rate per 1,000 patients/year was calculated for microvascular and cardiovascular complications, and death. Age, the ratio of non-HDL- to HDL-cholesterol, HbA1c, systolic blood pressure and smoking were significant predictors of cardiovascular events. A risk model was developed using these predictors. The UKPDS-RE and FRS-RS showed inadequate discrimination (Uno's C statistics 0.62 and 0.58, respectively) and calibration (24% overestimation and 51% underestimation, respectively) for predicting CHD risk. The internal discrimination and calibration of the developed model were acceptable for predicting fatal/non-fatal 2- and 5-, but not 10-year CHD and CVD risk. CONCLUSIONS/INTERPRETATION: This study is the first southern European validated population-derived model for predicting 5-year fatal/non-fatal CHD and CVD risk in patients with newly diagnosed type 2 diabetes.

Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort--a factor analysis.

A "Western" lifestyle characterized by physical inactivity and excess weight is associated with a number of metabolic and hormonal dysregulations, including increased circulating estrogen levels, hyperinsulinemia, hyperglycemia, and chronic inflammation. The same hormonal and metabolic axes might mediate the association between this lifestyle and the development of endometrial cancer. Using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study carried out in 10 European countries during 1992-2000, we conducted a factor analysis to delineate important components that summarize the variation explained by a set of biomarkers and to examine their association with endometrial cancer risk. Prediagnostic levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, estrone, estradiol, C-peptide, insulin-like growth factor-binding proteins 1 and 2, adiponectin, high- and low-density lipoprotein cholesterol, glucose, triglycerides, tumor necrosis factor (TNF) α, soluble TNF receptors 1 and 2, C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist were measured in 233 incident endometrial cancer cases and 446 matched controls. Factor analysis identified 3 components associated with postmenopausal endometrial cancer risk that could be labeled "insulin resistance/metabolic syndrome," "steroids," and "inflammation" factors. A fourth component, "lipids," was not significantly associated with endometrial cancer. In conclusion, besides the well-known associations of risk with sex hormones and insulin-regulated physiological axes, our data further support the hypothesis that inflammation factors play a role in endometrial carcinogenesis.

Concentrations and correlations of disinfection by-products in municipal drinking water from an exposure assessment perspective.

Although disinfection by-products (DBPs) occur in complex mixtures, studies evaluating health risks have been focused in few chemicals. In the framework of an epidemiological study on cancer in 11 Spanish provinces, we describe the concentration of four trihalomethanes (THMs), nine haloacetic acids (HAA), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), four haloacetonitries, two haloketones, chloropicrin and chloral hydrate and estimate correlations. A total of 233 tap water samples were collected in 2010. Principal component analyses were conducted to reduce dimensionality of DBPs. Overall median (range) level of THMs and HAAs was 26.4 (0.8-98.1) and 26.4 (0.9-86.9) µg/l, respectively (N=217). MX analysed in a subset (N=36) showed a median (range) concentration of 16.7 (0.8-54.1)ng/l. Haloacetonitries, haloketones, chloropicrin and chloral hydrate were analysed in a subset (N=16), showing levels from unquantifiable (<1 µg/l) to 5.5 µg/l (dibromoacetonitrile). Spearman rank correlation coefficients between DBPs varied between species and across areas, being highest between dibromochloromethane and dibromochloroacetic acid (r(s)=0.87). Principal component analyses of 13 DBPs (4 THMs, 9 HAAs) led 3 components explaining more than 80% of variance. In conclusion, THMs and HAAs have limited value as predictors of other DBPs on a generalised basis. Principal component analysis provides a complementary tool to address the complex nature of the mixture.

Dietary factors and in situ and invasive cervical cancer risk in the European prospective investigation into cancer and nutrition study.

Some dietary factors could be involved as cofactors in cervical carcinogenesis, but evidence is inconclusive. There are no data about the effect of fruits and vegetables intake (F&V) on cervical cancer from cohort studies. We examined the association between the intake of F&V and selected nutrients and the incidence of carcinoma in situ (CIS) and invasive squamous cervical cancer (ISC) in a prospective study of 299,649 women, participating in the European Prospective Investigation into Cancer and Nutrition study. Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CI). A calibration study was used to control measurement errors in the dietary questionnaire. After a mean of 9 years of follow-up, 253 ISC and 817 CIS cases were diagnosed. In the calibrated model, we observed a statistically significant inverse association of ISC with a daily increase in intake of 100 g of total fruits (HR 0.83; 95% CI 0.72-0.98) and a statistically nonsignificant inverse association with a daily increase in intake of 100 g of total vegetables (HR 0.85: 95% CI 0.65-1.10). Statistically nonsignificant inverse associations were also observed for leafy vegetables, root vegetables, garlic and onions, citrus fruits, vitamin C, vitamin E and retinol for ISC. No association was found regarding beta-carotene, vitamin D and folic acid for ISC. None of the dietary factors examined was associated with CIS. Our study suggests a possible protective role of fruit intake and other dietary factors on ISC that need to be confirmed on a larger number of ISC cases.

Tumor necrosis factor (TNF)-α, soluble TNF receptors and endometrial cancer risk: the EPIC study.

Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-α (TNF-α), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case-control study nested within the European prospective investigation into cancer and nutrition (EPIC) to examine the association of TNF-α and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two-hundred-seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two-sided. We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF-α (odds ratio [OR]: 1.73, 95% CI: 1.09-2.73, P(trend) = 0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99-2.86, P(trend) = 0.07) and sTNFR2 (OR: 1.53, 95%CI: 0.92-2.55, P(trend) = 0.03) after adjustment for body-mass-index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C-peptide had minor effect on risk estimates. Our data show that elevated prediagnostic concentrations of TNF-α and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies.

Using surveillance data to estimate pandemic vaccine effectiveness against laboratory confirmed influenza A(H1N1)2009 infection: two case-control studies, Spain, season 2009-2010.

BACKGROUND: Physicians of the Spanish Influenza Sentinel Surveillance System report and systematically swab patients attended to their practices for influenza-like illness (ILI). Within the surveillance system, some Spanish regions also participated in an observational study aiming at estimating influenza vaccine effectiveness (cycEVA study). During the season 2009-2010, we estimated pandemic influenza vaccine effectiveness using both the influenza surveillance data and the cycEVA study. METHODS: We conducted two case-control studies using the test-negative design, between weeks 48/2009 and 8/2010 of the pandemic season. The surveillance-based study included all swabbed patients in the sentinel surveillance system. The cycEVA study included swabbed patients from seven Spanish regions. Cases were laboratory-confirmed pandemic influenza A(H1N1)2009. Controls were ILI patients testing negative for any type of influenza. Variables collected in both studies included demographic data, vaccination status, laboratory results, chronic conditions, and pregnancy. Additionally, cycEVA questionnaire collected data on previous influenza vaccination, smoking, functional status, hospitalisations, visits to the general practitioners, and obesity. We used logistic regression to calculate adjusted odds ratios (OR), computing pandemic influenza vaccine effectiveness as (1-OR)*100. RESULTS: We included 331 cases and 995 controls in the surveillance-based study and 85 cases and 351 controls in the cycEVA study. We detected nine (2.7%) and two (2.4%) vaccine failures in the surveillance-based and cycEVA studies, respectively. Adjusting for variables collected in surveillance database and swabbing month, pandemic influenza vaccine effectiveness was 62% (95% confidence interval (CI): -5; 87). The cycEVA vaccine effectiveness was 64% (95%CI: -225; 96) when adjusting for common variables with the surveillance system and 75% (95%CI: -293; 98) adjusting for all variables collected. CONCLUSION: Point estimates of the pandemic influenza vaccine effectiveness suggested a protective effect of the pandemic vaccine against laboratory-confirmed influenza A(H1N1)2009 in the season 2009-2010. Both studies were limited by the low vaccine coverage and the late start of the vaccination campaign. Routine influenza surveillance provides reliable estimates and could be used for influenza vaccine effectiveness studies in future seasons taken into account the surveillance system limitations.

Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta-analysis of prospective studies.

Several prospective studies have shown a moderate positive association between increasing circulating insulin-like growth factor-I (IGF-I) levels and colorectal cancer risk. However, the associations were often statistically nonsignificant, and the relationship of cancer risk with IGF-I's major binding protein, IGFBP-3, showed major discrepancies between studies. We investigated the association of colorectal cancer risk with serum IGF-I, total and intact IGFBP-3, in a case-control study nested within the EPIC cohort (1,121 cases of colorectal cancer and 1,121 matched controls). Conditional logistic regression was used to adjust for possible confounders. Our present study results were combined in a meta-analysis with those from 9 previous prospective studies to examine the overall evidence for a relationship of prediagnostic serum IGF-I with colorectal cancer risk. In the EPIC study, serum concentrations of IGF-I and IGFBP-3 showed no associations with risk of colorectal cancer overall. Only in subgroup analyses did our study show moderate positive associations of IGF-I levels with risk, either among younger participants only (and only for colon cancer) or among participants whose milk intakes were in the lowest tertile of the population distribution (RR for an increase of 100 ng/ml = 1.43 [95% CI = 1.13-1.93]). Nevertheless, in the meta-analysis a modest positive association remained between serum IGF-I and colorectal cancer risk overall (RR = 1.07 [1.01-1.14] for 1 standard deviation increase in IGF-I). Overall, data from our present study and previous prospective studies combined indicate a relatively modest association of colorectal cancer risk with serum IGF-I.

Author Correction: Validating a breast cancer score in Spanish women. The MCC-Spain study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The Relation of CUN-BAE Index with Body Mass Index and Waist Circumference in Adults Aged 50 to 85 Years: The MCC-Spain Study.

Backgound: Traditional anthropometrics such as body mass index (BMI) or waist circumference (WC) do not fully capture the complex biology of body fat (BF) in the elderly. The Clinica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) index, based on BMI, is proposed as a better indicator of BF. However, its relation with BMI is not clear. The aim was to compare the agreement between CUN-BAE, BMI, and WC in those aged ≥50 years. Methods: A cross-sectional sample of 3153 Caucasian healthy adults was taken from the MCC-Spain study. The Pearson's correlation and its 95% confidence interval (CI), adiposity distribution, and Kappa Index (95%CI) were calculated. Results: The correlation of CUN-BAE with WC is 0.18 (95%CI 0.14-0.21) and that with BMI is moderate (r 0.58; 95%CI 0.55-0.60), but both increased strongly by sex. Agreement (normal weight/overweight/obesity) of CUN-BAE with BMI is 7% and with WC is 18%. Conclusions: The correlation and the degree of agreement of CUN-BAE with BMI and WC are low in individuals aged over 50, but it is higher by sex. Thus, this different criterion of obesity may have clinical applications. More studies with a gold standard are needed to evaluate the CUN-BAE in elderly adults.

Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause.

Dyslipidemia and statin use have been associated with colorectal cancer (CRC), but prospective studies have shown mixed results. We aimed to determine whether dyslipidemia is causally linked to CRC risk using a Mendelian randomization approach and to explore the association of statins with CRC. A case-control study was performed including 1336 CRC cases and 2744 controls (MCC-Spain). Subjects were administered an epidemiological questionnaire and were genotyped with an array which included polymorphisms associated with blood lipids levels, selected to avoid pleiotropy. Four genetic lipid scores specific for triglycerides (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), or total cholesterol (TC) were created as the count of risk alleles. The genetic lipid scores were not associated with CRC. The ORs per 10 risk alleles, were for TG 0.91 (95%CI: 0.72-1.16, p = 0.44), for HDL 1.14 (95%CI: 0.95-1.37, p = 0.16), for LDL 0.97 (95%CI: 0.81-1.16, p = 0.73), and for TC 0.98 (95%CI: 0.84-1.17, p = 0.88). The LDL and TC genetic risk scores were associated with statin use, but not the HDL or TG. Statin use, overall, was a non-significant protective factor for CRC (OR 0.84; 95%CI: 0.70-1.01, p = 0.060), but lipophilic statins were associated with a CRC risk reduction (OR 0.78; 95%CI 0.66-0.96, p = 0.018). Using the Mendelian randomization approach, our study does not support the hypothesis that lipid levels are associated with the risk of CRC. This study does not rule out, however, a possible protective effect of statins in CRC by a mechanism unrelated to lipid levels.