Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

Application of a digital PCR method for WT1 to myeloid neoplasms in CR and deep ELN WT1 molecular response (< 10 copies).

Bone marrow WT1 mRNA levels assessed by the ELN method are useful to establish prognostic correlations in myeloid malignancies treated with chemotherapy or hematopoietic stem cell transplantation (HCT). Those patients with WT1 levels below ten copies have a good outcome. However, some of these patients relapse. To further characterize this group of cases, we applied a new and sensitive digital (ddPCR) WT1 method. A consecutive series of 49 patients with treated myeloid malignancies and with an ELN WT1 quantitation of < 10 copies were included in the study. All cases (47 AML and 2 MDS) have received intensive chemotherapy or HCT. One to four micrograms of total RNA were retrotranscribed to obtain ≥ 10,000 ABL1 copies using the ELN protocol. Only those cases with a good quality cDNA were used in the ddPCR WT1 test. The ddPCR Gene Expression WT1 Assay of Bio-Rad© was used to perform the PCR amplification, and the microdroplets were quantified in the Bio-Rad's QX200 droplet reader. Eighteen patients showed a negative WT1 ddPCR assay (0 copies/µl), whereas 31 cases were positive (results ranged from 1 to 15.2 copies/µl). Survival analysis showed statistically significant differences in terms of OS between both groups, 83 ± 8% vs. 46 ± 9% (p = 0.024). A statistically significant correlation was also found between ddPCRWT1 results and CD123+ cell number detected by flow cytometry (p = 0.024). Larger series of patients tested with the current ddPCRWT1 method will solve whether it could be used to stratify patients with myeloid malignancies achieving deep WT1 molecular response (< 10 copies).

Impact of anaemia on health-related quality of life and cardiac remodelling in patients with lower risk myelodysplastic syndromes. Results of GlobQoL study.

The aim of this study was to analyse the eventual changes in health-related quality of life (HRQoL) and left ventricular function (LVF) over a 1-year follow-up period in a cohort of patients with lower risk myelodysplastic syndromes (MDS) receiving standard supportive treatment, in order to identify potential clues for early clinical intervention, as well as to analyse how they relate to haemoglobin levels and other aspects of the disease. A total of 39 adult anaemic patients with lower risk MDS were included in a prospective, observational, multi-centre study. Changes in performance status, functional capacity and HRQoL were collected by using standardised measures (ECOG scale; SPPB, Short Physical Performance Battery; SF-36, Short-Form 36 questionnaire; QLQ-C30, Quality of Life Core Questionnaire; FACT-An, Functional Assessment of Cancer Therapy-Anaemia scale questionnaires respectively). Need for transfusion (Linear Analogue Scale Assessment), as perceived independently by the patient and the haematologist, was also recorded. No changes in HRQoL (or LVF) were found, except for slight reductions in SF-36 physical function (P = 0.034), SPPB gait speed (P = 0.038) and FACT-An score (P = 0.029), all without apparent immediate clinical relevance for HRQoL, that were unrelated to changes in haemoglobin level. Periodical evaluation of gait speed may assist the clinician in early detection of patient's occult functional decline before it becomes clinically relevant.

Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct.

AIMS/HYPOTHESIS: Consumption of sugar-sweetened beverages has been shown, largely in American populations, to increase type 2 diabetes incidence. We aimed to evaluate the association of consumption of sweet beverages (juices and nectars, sugar-sweetened soft drinks and artificially sweetened soft drinks) with type 2 diabetes incidence in European adults. METHODS: We established a case-cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. After exclusions, the final sample size included 11,684 incident cases and a subcohort of 15,374 participants. Cox proportional hazards regression models (modified for the case-cohort design) and random-effects meta-analyses were used to estimate the association between sweet beverage consumption (obtained from validated dietary questionnaires) and type 2 diabetes incidence. RESULTS: In adjusted models, one 336 g (12 oz) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 (95% CI 1.09, 1.38) and 1.52 (95% CI 1.26, 1.83), respectively. After further adjustment for energy intake and BMI, the association of sugar-sweetened soft drinks with type 2 diabetes persisted (HR 1.18, 95% CI 1.06, 1.32), but the association of artificially sweetened soft drinks became statistically not significant (HR 1.11, 95% CI 0.95, 1.31). Juice and nectar consumption was not associated with type 2 diabetes incidence. CONCLUSIONS/INTERPRETATION: This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults.

Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort.

BACKGROUND: Evidence on associations between self-reported diabetes mellitus, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce. PATIENTS AND METHODS: We conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case-control subset, analyses were carried out in HCV/HBV-negative individuals. RESULTS: During 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00-3.13) and 2.17 (1.36-3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17-6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals. CONCLUSION(S): This study supports the hypothesis that diabetes is a risk factor for BTC (particularly GBC) and HCC. Further research is required to establish whether diabetes treatment or duration is associated with these cancers.

Caspofungin for the treatment of invasive fungal disease in hematological patients (ProCAS Study).

Caspofungin is an echinocandin with proven efficacy in invasive candidiasis (IC) and invasive aspergillosis (IA). This multicenter, prospective, non-comparative, observational ProCAS study was aimed to assess the effectiveness and safety of caspofungin in adult hematological patients with IC or IA under everyday clinical conditions. Favorable outcomes included complete and partial responses on the last day of caspofungin therapy. Safety was assessed up to 14 days post-caspofungin. A total of 115 patients (69 male) with a median age of 52 years (range, 23-78 years) were analyzed. Underlying disease was acute myeloid leukemia in 45 patients (39%), and 21 (18%) were allogeneic stem cell transplant recipients. Thirty-four (29.5%) patients had a diagnosis of IA and 26 (22.6%) had IC (candidemia). The median duration of caspofungin therapy was 14 days (range, 1-100). The overall favorable response rate was 77% (20/26) for patients with IC (69% first-line) and 79% (27/34) for those with IA. Antifungal therapy with caspofungin was generally well tolerated, only two (1.7%) patients having a non-serious drug-related adverse reaction. These results suggest that caspofungin, either alone or in combination, should be considered an effective and safe option for the treatment of invasive mycoses in patients with severe hematological disorders.

Incidence and prognostic impact of U2AF1 mutations and other gene alterations in myelodysplastic neoplasms with isolated 20q deletion.

BACKGROUND: In myelodysplastic neoplasms (MDS), the 20q deletion [del(20q)] is a recurrent chromosomal abnormality that it has a high co-occurrence with U2AF1 mutations. Nevertheless, the prognostic impact of U2AF1 in these MDS patients is uncertain and the possible clinical and/or prognostic differences between the mutation type and the mutational burden are also unknown. METHODS: Our study analyzes different molecular variables in 100 MDS patients with isolated del(20q). RESULTS & CONCLUSIONS: We describe the high incidence and negative prognostic impact of U2AF1 mutations and other alterations such as in ASXL1 gene to identify prognostic markers that would benefit patients to receive earlier treatment.

Alcohol consumption and risk of type 2 diabetes in European men and women: influence of beverage type and body size The EPIC-InterAct study.

OBJECTIVE: To investigate the association between alcohol consumption and type 2 diabetes, and determine whether this is modified by sex, body mass index (BMI) and beverage type. DESIGN: Multicentre prospective case-cohort study. SETTING: Eight countries from the European Prospective Investigation into Cancer and Nutrition cohort. SUBJECTS: A representative baseline sample of 16 154 participants and 12 403 incident cases of type 2 diabetes. INTERVENTIONS: Alcohol consumption assessed using validated dietary questionnaires. MAIN OUTCOME MEASURES: Occurrence of type 2 diabetes based on multiple sources (mainly self-reports), verified against medical information. RESULTS: Amongst men, moderate alcohol consumption was nonsignificantly associated with a lower incidence of diabetes with a hazard ratio (HR) of 0.90 (95% CI: 0.78-1.05) for 6.1-12.0 versus 0.1-6.0 g day(-1) , adjusted for dietary and diabetes risk factors. However, the lowest risk was observed at higher intakes of 24.1-96.0 g day(-1) with an HR of 0.86 (95% CI: 0.75-0.98). Amongst women, moderate alcohol consumption was associated with a lower incidence of diabetes with a hazard ratio of 0.82 (95% CI: 0.72-0.92) for 6.1-12.0 g day(-1) (P interaction gender <0.01). The inverse association between alcohol consumption and diabetes was more pronounced amongst overweight (BMI ≥ 25 kg m(-2) ) than normal-weight men and women (P interaction < 0.05). Adjusting for waist and hip circumference did not alter the results for men, but attenuated the association for women (HR=0.90, 95% CI: 0.79-1.03 for 6.1-12.0 g day(-1) ). Wine consumption for men and fortified wine consumption for women were most strongly associated with a reduced risk of diabetes. CONCLUSIONS: The results of this study show that moderate alcohol consumption is associated with a lower risk of type 2 diabetes amongst women only. However, this risk reduction is in part explained by fat distribution. The relation between alcohol consumption and type 2 diabetes was stronger for overweight than normal-weight women and men.

Major dietary patterns and risk of coronary heart disease in middle-aged persons from a Mediterranean country: the EPIC-Spain cohort study.

BACKGROUND AND AIM: No previous study has assessed the association between major dietary patterns and the risk of coronary heart disease (CHD) in a large cohort from a Mediterranean country. METHODS AND RESULTS: We studied prospectively 40,757 persons, aged 29-69 years, participating in the Spanish cohort of the EPIC study. Food consumption was collected between 1992 and 1996 with a validated history method. Individuals were followed-up until 2004 through record linkage with hospital discharge registers, population-based registers of myocardial infarction, and mortality registers to ascertain CHD events (fatal and non-fatal acute myocardial infarction or angina requiring revascularization). Two major dietary patterns were identified from factor analysis. The first pattern was labeled as Westernized, because of the frequent consumption of refined cereals and red meat; the second was called the evolved Mediterranean pattern, because of the frequent intake of plant-based foods and olive oil. During a median follow-up of 11 years, 606 CHD events were ascertained. No association was found between the Westernized pattern and CHD risk. In contrast, the score for the evolved Mediterranean pattern was inversely associated with CHD risk (p for trend = 0.0013); when compared with the lowest quintile of the evolved Mediterranean pattern score, the multivariable hazard ratios for CHD were 0.77 (95% confidence interval 0.61-0.98) for the second quintile, 0.64 (95% CI 0.50-0.83) for the third quintile, 0.56 (95% CI 0.43-0.73) for the fourth quintile, and 0.73 (95% CI 0.57-0.94) for the fifth quintile. CONCLUSION: A Mediterranean diet, as consumed in this study population, was associated with a lower risk of CHD.

Design and cohort description of the InterAct Project: an examination of the interaction of genetic and lifestyle factors on the incidence of type 2 diabetes in the EPIC Study.

AIMS/HYPOTHESIS: Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. This case-cohort study aims to investigate how genetic and potentially modifiable lifestyle and behavioural factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes. METHODS: Incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from eight of the ten EPIC countries were ascertained and verified. Prentice-weighted Cox regression and random-effects meta-analyses were used to investigate differences in diabetes incidence by age and sex. RESULTS: A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre-stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes who were randomly selected into the subcohort (n = 778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years; 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist circumference values were 29.4 kg/m(2) and 102.7 cm in men, and 30.1 kg/m(2) and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall HR of 1.56 (95% CI 1.48-1.64) for a 10 year age difference, adjusted for sex. A male excess in the risk of incident diabetes was consistently observed across all countries, with a pooled HR of 1.51 (95% CI 1.39-1.64), adjusted for age. CONCLUSIONS/INTERPRETATION: InterAct is a large, well-powered, prospective study that will inform our understanding of the interplay between genes and lifestyle factors on the risk of type 2 diabetes development.

Association of plasma markers of cholesterol homeostasis with metabolic syndrome components. A cross-sectional study.

BACKGROUND AND AIMS: Increased plasma phytosterols, which reflect enhanced cholesterol absorption, have been related to an increased risk of cardiovascular disease (CVD). However, high CVD risk conditions, such as obesity, diabetes and the metabolic syndrome (MetS) have been associated with reduced cholesterol absorption. We investigated associations between plasma noncholesterol sterols and MetS components. METHODS AND RESULTS: With a cross-sectional design, we related MetS components to plasma noncholesterol sterol-to-cholesterol ratios measured by gas chromatography in 674 dyslipidemic patients and 361 healthy subjects participating in a prospective cohort study. Plasma phytosterol-to-cholesterol ratios were inversely associated with all components of the MetS. In the dyslipidemic group, multivariable analyses showed that a 1-SD increase in sitosterol-to-cholesterol ratio was associated with a reduced risk for any MetS feature, ranging from 0.57 (95% CI, 0.45 to 0.71) for visceral adiposity to 0.82 (95% CI, 0.69 to 0.98) for high blood pressure. The risk of having MetS was nearly halved, with ORs of 0.49 (95% CI, 0.38 to 0.64) or 0.56 (95% CI, 0.44-0.70), depending on the definition. Results were opposed for plasma lathosterol, a marker of cholesterol synthesis. Most findings were reproduced in the healthy cohort. ApoE genotype was unrelated to plasma noncholesterol sterols. CONCLUSION: In both dyslipidemic and healthy populations, MetS is associated with increased plasma lathosterol, a cholesterol synthesis marker, and decreased plasma sitosterol, a marker of cholesterol absorption. Elevated plasma phytosterols related to a lower frequency of cardiometabolic risk factors, suggesting that they are associated with a reduced CVD risk.

Different methylation signatures at diagnosis in patients with high-risk myelodysplastic syndromes and secondary acute myeloid leukemia predict azacitidine response and longer survival.

BACKGROUND: Epigenetic therapy, using hypomethylating agents (HMA), is known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy and/or allogeneic stem cell transplantation. However, response rates to HMA are low and there is an unmet need in finding prognostic and predictive biomarkers of treatment response and overall survival. We performed global methylation analysis of 75 patients with high-risk MDS and secondary AML who were included in CETLAM SMD-09 protocol, in which patients received HMA or intensive treatment according to age, comorbidities and cytogenetic. RESULTS: Unsupervised analysis of global methylation pattern at diagnosis did not allow patients to be differentiated according to the cytological subtype, cytogenetic groups, treatment response or patient outcome. However, after a supervised analysis we found a methylation signature defined by 200 probes, which allowed differentiating between patients responding and non-responding to azacitidine (AZA) treatment and a different methylation pattern also defined by 200 probes that allowed to differentiate patients according to their survival. On studying follow-up samples, we confirmed that AZA decreases global DNA methylation, but in our cohort the degree of methylation decrease did not correlate with the type of response. The methylation signature detected at diagnosis was not useful in treated samples to distinguish patients who were going to relapse or progress. CONCLUSIONS: Our findings suggest that in a subset of specific CpGs, altered DNA methylation patterns at diagnosis may be useful as a biomarker for predicting AZA response and survival.

Double-strand break DNA repair genotype predictive of later mortality and cancer incidence in a cohort of non-smokers.

We followed-up for mortality and cancer incidence 1088 healthy non-smokers from a population-based study, who were characterized for 22 variants in 16 genes involved in DNA repair pathways. Follow-up was 100% complete. The association between polymorphism and mortality or cancer incidence was analyzed using Cox Proportional Hazard regression models. Ninety-five subjects had died in a median follow-up time of 78 months (inter-quartile range 59-93 months). None of the genotypes was clearly associated with total mortality, except variants for two Double-Strand Break DNA repair genes, XRCC3 18067 C>T (rs#861539) and XRCC2 31479 G>A (rs#3218536). Adjusted hazard ratios were 2.25 (1.32-3.83) for the XRCC3 C/T genotype and 2.04 (1.00-4.13) for the T/T genotype (reference C/C), and 2.12 (1.14-3.97) for the XRCC2 G/A genotype (reference G/G). For total cancer mortality, the adjusted hazard ratios were 3.29 (1.23-7.82) for XRCC3 C/T, 2.84 (0.81-9.90) for XRCC3 T/T and 3.17 (1.21-8.30) for XRCC2 G/A. With combinations of three or more adverse alleles, the adjusted hazard ratio for all cause mortality was 17.29 (95% C.I. 8.13-36.74), and for all incident cancers the HR was 5.28 (95% C.I. 2.17-12.85). Observations from this prospective study suggest that polymorphisms of genes involved in the repair of DNA double-strand breaks significantly influence the risk of cancer and non-cancer disease, and can influence mortality.

Physical activity and lung cancer among non-smokers: a pilot molecular epidemiological study within EPIC.

The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by (32)P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35-0.90), higher GSH levels (+1.87 micromol GSH g(-1) haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38-2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84-1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.

Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium.

The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.

Aromatic DNA adducts and polymorphisms in metabolic genes in healthy adults: findings from the EPIC-Spain cohort.

Aromatic compounds such as polycyclic aromatic hydrocarbons, arylamines and heterocyclic amines require metabolic activation to form metabolites able to bind to DNA, a process mediated by polymorphic enzymes. We measured aromatic DNA adducts in white blood cells by the (32)P-post-labelling assay in a sample of 296 healthy adults (147 men and 149 women) from five regions of Spain. We also analyzed functional polymorphisms in the metabolic genes CYP1A1, CYP1A2, EPHX1, GSTM1, GSTT1, NAT2 and SULT1A1. A significant increased level of DNA aromatic adducts was found related to the fast oxidation-hydrolysis phenotype defined by the polymorphism I462V in CYP1A1, the allele A in IVS1-154C>A of CYP1A2 and the combination Tyrosine-Arginine for Y113H and H139R of EPHX1. Geometric means (adducts per 10(-9) normal nucleotides) were 2.17, 4.04 and 6.30 for slow, normal and fast phenotypes, respectively (P-trend = 0.01). Slow acetylation by NAT2 was associated with a significant decrease in adduct level; subjects with slow alleles *5A and *7A/B had in average 1.56 x 10(-9)adducts, as compared with 5.60 for those with normal NAT2 activity (P-value = 0.01). No association was seen with polymorphisms of other metabolic genes such as GSTM1, GSTT1 or SULT1A1. We concluded that the metabolic pathways of oxidation, hydrolysis and acetylation are relevant to the formation of bulky DNA adducts. This could suggest a potential involvement of aromatic compounds in the formation of such adducts; however, given lack of specificity of the post-labeling assay, a firm conclusion cannot be drawn.

Prevalence of dementia and cognitive impairment in Southeastern Spain: the Ariadna study.

OBJECTIVES: To estimate the prevalence of amnestic mild cognitive impairment (aMCI), cognitive impairment, no dementia (CIND) and dementia in a general elderly population and to examine the associated socio-demographic factors. METHODS: The Ariadna study is a population-based cross-sectional study of cognitive function involving 1074 individuals aged 65-96 years from the Murcia Region of southeastern Spain. Prevalence, adjusted odds ratio (OR) and 95% confidence intervals (CI) were calculated. RESULTS: The overall prevalence was 8.7% (95% CI 7.1-10.5) for aMCI, 14.5% (95% CI 12.4-16.8) for CIND and 5.5% (95% CI 4.3-7.1) for dementia. Dementia was associated with age (OR 1.13 95% CI 1.09-1.18 for a 1-year increase in age). Illiterate subjects were more likely to present aMCI (OR 2.59; 95% CI 1.09-6.14) and dementia (OR 4.09; 95% CI 1.28-13.08) than subjects with secondary or higher education. Rural area residents (OR 2.13, 95% CI 1.07-4.24) and women (OR 1.53, 95% CI 1.06-2.22) were more likely to have CIND. CONCLUSION: The prevalence of dementia was low, despite a high prevalence of aMCI and CIND. Dementia was strongly associated with age and education. CIND was associated with living in a rural area and with female sex, while aMCI was associated with illiteracy.

Polychlorinated biphenyls in Spanish adults: determinants of serum concentrations.

BACKGROUND: Polychlorinated biphenyls (PCBs) are persistent compounds that may pose an environmental hazard to humans, food being the main source of exposure for the general population. OBJECTIVE: To measure the serum concentrations of the main PCBs in subjects from the general population in Spain, and to assess potential determinants of such concentrations. METHODS: Serum was obtained from blood samples of 953 subjects aged 35-64 years, residents in five Spanish regions (three from the North and two from the South), randomly selected from the EPIC-Spain cohort. Blood collection took place during 1992-1996 and four PCB congeners (118, 138, 153 and 180) were determined by means of gas chromatography with electron-capture detection (GC-ECD). RESULTS: The concentration of total PCBs was 459 ng/g lipids (or 3.1 microg/l); the corresponding figures for PCB 153 were 186 ng/g lipids and 1.25 microg/l. Men had higher values than women, PCB levels increased with age, and serum concentration of PCBs was higher in northern regions. Body mass index (BMI) was inversely related to PCB concentrations, and fish intake was the dietary factor showing the greatest association with serum PCBs. The pattern described was similar for each congener separately. CONCLUSIONS: We found concentrations similar to those reported in European countries where blood collection was carried during the same period. Regional differences within Spain are not fully explained by anthropometric or dietary factors. The inverse association with BMI suggests that in the mid-1990s there was still ongoing or recent exposure to PCBs in Spain.

Incidence of acute myocardial infarction in the Spanish epic cohort.

BACKGROUND: There is some evidence that Mediterranean diet reduces risk of ischemic heart disease, and this is to be investigated in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). In this paper we present the incidence of acute myocardial infarction (AMI) in four EPIC Spanish cohorts. METHOD: Incidence cases were ascertained in EPIC cohort during the follow up period (from recruitment to the end of 2004), by means of self-report questionnaires, hospital morbidity and mortality registries, and population AMI registries. Analysis was restricted to aged 45 to 74. The present study included data from 13,704 women and 19,410 men, after excluding a priori participants with prevalent AMI. Age standardized incidence rate for each cohort was estimated and compared with the available population rates. RESULTS: The Median duration of follow-up was 9.3 years, yielding a total of 297,704 person-years. 391 men and 99 women presented AMI in the four cohorts studied. Age standardized AMI rates in men of the EPIC cohorts go from the lowest 302 (CI: 268-335) per 100.000 person-year of Gipuzkoa to the highest 330 (CI: 293-367) of Navarra. Women in Navarra presented the lowest AMI incidence with 60 (CI: 43-77) per 100,000 and the highest was observed in Murcia (114, CI: 91-137). The AMI incidence in all EPIC centres are close to the population incidence rates and in any case these are within the EPIC 95% CI. CONCLUSIONS: The comparison of incidence in EPIC with population rates shows very good agreement for acute myocardial infarction.

Blood pressure and risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition.

Elevated blood pressure has been implicated as a risk factor for renal cell carcinoma (RCC), but prospective studies were confined to men and did not consider the effect of antihypertensive medication. The authors examined the relation among blood pressure, antihypertensive medication, and RCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). Blood pressure was measured in 296,638 women and men, recruited in eight European countries during 1992-1998, 254,935 of whom provided information on antihypertensive medication. During a mean follow-up of 6.2 years, 250 cases of RCC were identified. Blood pressure was independently associated with risk of RCC. The relative risks for the highest versus the lowest category of systolic (>/=160 mmHg vs. <120 mmHg) and diastolic (>/=100 mmHg vs. <80 mmHg) blood pressures were 2.48 (95% confidence interval: 1.53, 4.02) and 2.34 (95% confidence interval: 1.54, 3.55). Risk estimates did not significantly differ according to sex or use of antihypertensive medication. Individuals taking antihypertensive drugs were not at a significantly increased risk unless blood pressure was poorly controlled. These results support the hypothesis that hypertension, rather than its medications, increases the risk of RCC in both sexes, while effective blood pressure control may lower the risk.