Carmen Martínez

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.

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.

Validity of self-reported prevalent cases of stroke and acute myocardial infarction in the Spanish cohort of the EPIC study

Background Information on the validity of self-reported cases of stroke and acute myocardial infarction (AMI) is varied. The aim of this study was to assess the validity and agreement of self-reported prevalent cases of stroke and AMI in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods At recruitment, 1992–1996, and in the follow-up (3 years after recruitment), each participant in the Spanish EPIC cohort (15 630 men and 25 808 women) was asked if a doctor had ever said that they had had a stroke or AMI, and the results were compared with information available in medical records. Validity of self-reported prevalent cases of stroke and AMI was examined by calculating sensitivity, specificity, positive predictive values and κ statistics. Results The sensitivity of self-reported prevalent cases of stroke was 81.3% and that for AMI was 97.7%. The positive predictive value was 22.2% and 60.7% for stroke and AMI, respectively, whereas specificity was very high (>99%) for both diseases. The agreement between self-report questionnaire results and medical records was substantial (κ=0.75) for AMI but not for stroke (κ=0.35). Conclusion Self-reported information on stroke and AMI included in the EPIC questionnaire is a valid instrument for the assessment of AMI disease but should be used with caution in stroke.

Vitamins B2 and B6 and Genetic Polymorphisms Related to One-Carbon Metabolism as Risk Factors for Gastric Adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition

B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5′-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC risk were calculated with conditional logistic regression, adjusted for Helicobacter pylori infection status and smoking status. Adjusted relative risks per quartile (95% confidence interval, Ptrend) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and 0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in individuals with severe chronic atrophic gastritis. The polymorphisms were not associated with GC risk and did not modify the observed vitamin-cancer associations. In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk. Cancer Epidemiol Biomarkers Prev; 19(1); 28–38

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.

Photocatalytic degradation of five sulfonylurea herbicides in aqueous semiconductor suspensions under natural sunlight

In the present study, the photocatalytic degradation of five sulfonylurea herbicides (chlorsulfuron, flazasulfuron, nicosulfuron, sulfosulfuron and triasulfuron) has been investigated in aqueous suspensions of zinc oxide (ZnO), tungsten (VI) oxide (WO(3)), tin (IV) oxide (SnO(2)) and zinc sulfide (ZnS) at pilot plant scale under natural sunlight. Photocatalytic experiments, especially those involving ZnO photocatalysis, showed that the addition of semiconductors in tandem with the oxidant (Na(2)S(2)O(8)) strongly enhances the degradation rate of the herbicides in comparisons carried out with photolytic tests. The degradation of the herbicides follows a first order kinetics according to the Langmuir-Hinshelwood model. In our conditions, the amount of time required for 50% of the initial pesticide concentration to dissipate (t(½)) ranged from 8 to 27 min (t(30W)=0.3-1.2 min) for sulfosulfuron and chlorsulfuron, respectively in the ZnO/Na(2)S(2)O(8) system. None of the studied herbicides was found after 120 min of illumination (except chlorsulfuron, 0.2 μg L(-1)).

Validity of self reported diagnoses of cancer in a major Spanish prospective cohort study

Introduction: This study aims to assess the validity of self reported diagnoses of cancer by persons recruited for the Spanish EPIC (European prospective investigation into cancer and nutrition) cohort study and to identify variables associated with correctly reporting a diagnosis of cancer. Methods: 41 440 members of EPIC were asked at the time of recruitment whether they had been diagnosed with cancer and the year of diagnosis and site. The process of validating self reported diagnoses of cancer included comparison of the cohort database with the data from the population based cancer registries. Cancer diagnostic validity tests were calculated. The association between a correct report and certain sociodemographic, tumour related, or health related variables were analysed by logistic regression. Results: The overall sensitivity of self reported diagnoses of cancer is low (57.5%; 95% CI: 51.9 to 63.0), the highest values being shown by persons with a higher level of education or with a family history of cancer and the lowest values by smokers. Breast and thyroid cancers are those with the highest diagnostic validity and uterus, bladder, and colon-rectum those with the lowest. In both sexes the variables showing a significant association with a correct report of cancer are: higher education level, number of previous pathologies, invasive tumour, and, in women, a history of gynaecological surgery. Conclusions: The overall sensitivity of self reported diagnoses of cancer is comparatively low and it is not recommended in epidemiological studies for identifying tumours. However, self reported diagnoses might be highly valid for certain tumour sites, malignant behaviour, and average to high levels of education.

Involvement of KATP channels in diethylstilbestrol-induced relaxation in rat aorta

The estrogens prevent cardiovascular diseases that among other effects could be related to the modulation of the vascular tone via modifying ionic channel permeability. ATP-sensitive K(+) (K(ATP)) channels seem to be involved in diethylstilbestrol-induced relaxation in isolated rat aorta precontracted by noradrenaline (30 nM), since the effect is inhibited by glibenclamide (1--10 microM), and 1 mM tetraethylammonium, but not by 30 mM tetraethylammonium or paxilline. The antiestrogen tamoxifen, the inhibitor of protein kinase A, Rp-cAMPS, and the inhibitor of ornithine decarboxylase, difluoromethylornithine, antagonized diethylstilbestrol-induced relaxation. The association of glibenclamide with these compounds separately did not modify the effect of glibenclamide alone on diethylstilbestrol-induced relaxation. Functional K(ATP) channels are present in rat aorta, since diazoxide induced relaxation sensitive to glibenclamide. Papaverine, dibutyryl cyclic AMP and spermine relaxed isolated rat aorta although this was not sensitive to glibenclamide. The relaxation to forskolin was antagonized by glibenclamide. We conclude that diethylstilbestrol-induced relaxation in rat aorta is related to the modulation of K(ATP) channels. Cyclic AMP-dependent mechanisms and polyamine synthesis may mediate this modulation.

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.

Gonadectomy Eliminates Endothelium-Dependent Diethylstilbestrol-Induced Relaxant Effect in Rat Aorta

The effects of gender and castration of rats on diethylstilbestrol-induced, endothelium-dependent and endothelium-independent relaxation in rat aorta strips were studied. For this, male and female control and castrated rats were used. Diethylstilbestrol elicited a concentration-dependent (1–30 µmol/l) relaxation of isolated rat aorta. The effect was significantly higher in the presence of endothelium in aorta strips of the control group and also in female as compared with male rats. This effect is NO-dependent, since it is inhibited by NG-methyl-L-arginine. Castration of the rats suppressed the endothelium-dependent relaxation, and it was similar to that induced in the absence of endothelium. Acetylcholine-induced relaxation was not suppressed by castration. The acetylcholine-induced relaxation was decreased in aorta strips previously relaxed by diethylstilbestrol. There are no gender differences in the diethylstilbestrol-induced, endothelium-independent component of the relaxation, nor is it modified by the hormonal environment. Therefore, diethylstilbestrol-induced, endothelium-dependent relaxation in rat aorta strips is modulated by the hormonal status of the rats.