Adonina Tardón

University of Oviedo, Oviedo, Asturias, Spain

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Publications (171)828.52 Total impact

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    ABSTRACT: BACKGROUND: Vitamin D status during prenatal brain development may influence risk of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood. However, there are no prospective studies addressing this hypothesis. We aimed to examine whether maternal vitamin D status in pregnancy is associated with risk of ADHD-like symptoms in offspring. METHODS: We conducted a prospective study analyzing data from 1,650 mother-child pairs from five birth cohorts embedded in the INMA Project (Spain, 1997-2008). Maternal vitamin D status in pregnancy was estimated by measuring plasma concentration of 25-hydroxyvitamin D3 [25(OH)D3] at 13 weeks of gestation. Children were assessed by teachers for ADHD-like symptoms at ages 4-5 years using the Diagnostic and Statistical Manual of Mental Disorders ADHD form list. RESULTS: After adjustment, the number of total ADHD-like symptoms in children decreased by 11% per 10 ng/ml increment of maternal 25(OH)D3 concentration (incidence rate ratio [IRR] = 0.89; 95% confidence interval [CI] = 0.80, 0.98). Similarly, the number of symptoms in the ADHD subscales decreased in relation to higher maternal 25(OH)D3 concentration (IRR per 10 ng/ml increment = 0.89; 95% CI = 0.79, 0.99 for the inattention scale; and IRR = 0.88; 95% CI = 0.78, 0.99 for the hyperactivity-impulsivity scale). Using diagnostic criteria, we found an association of increasing maternal 25(OH)D3 with a lower risk of ADHD DSM-IV (relative risk ratio per 10 ng/ml increment = 0.87; 95% CI = 0.72, 1.06) and ICD-10 hyperkinetic disorder (relative risk ratio = 0.72; 95% CI = 0.49, 1.04) in children. CONCLUSION: Higher maternal circulating levels of 25(OH)D3 in pregnancy are associated with lower risk of developing ADHD-like symptoms in childhood.
    Epidemiology 04/2015; · 6.18 Impact Factor
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    ABSTRACT: Vitamin D status during prenatal brain development may influence risk of attention deficit and hyperactivity disorder (ADHD) symptoms in childhood. However, there are no prospective studies addressing this hypothesis. We aimed to examine whether maternal vitamin D status in pregnancy is associated with risk of ADHD-like symptoms in offspring. We conducted a prospective study analyzing data from 1,650 mother-child pairs from five birth cohorts embedded in the INMA Project (Spain, 1997-2008). Maternal vitamin D status in pregnancy was estimated by measuring plasma concentration of 25-hydroxyvitamin D3 [25(OH)D3] at 13 weeks of gestation. Children were assessed by teachers for ADHD-like symptoms at ages 4-5 years using the Diagnostic and Statistical Manual of Mental Disorders ADHD form list. After adjustment, the number of total ADHD-like symptoms in children decreased by 11% per 10 ng/ml increment of maternal 25(OH)D3 concentration (incidence rate ratio [IRR] = 0.89; 95% confidence interval [CI] = 0.80, 0.98). Similarly, the number of symptoms in the ADHD subscales decreased in relation to higher maternal 25(OH)D3 concentration (IRR per 10 ng/ml increment = 0.89; 95% CI = 0.79, 0.99 for the inattention scale; and IRR = 0.88; 95% CI = 0.78, 0.99 for the hyperactivity-impulsivity scale). Using diagnostic criteria, we found an association of increasing maternal 25(OH)D3 with a lower risk of ADHD DSM-IV (relative risk ratio per 10 ng/ml increment = 0.87; 95% CI = 0.72, 1.06) and ICD-10 hyperkinetic disorder (relative risk ratio = 0.72; 95% CI = 0.49, 1.04) in children. Higher maternal circulating levels of 25(OH)D3 in pregnancy are associated with lower risk of developing ADHD-like symptoms in childhood.
    Epidemiology (Cambridge, Mass.) 04/2015; DOI:10.1097/EDE.0000000000000292 · 6.18 Impact Factor
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    ABSTRACT: OBJECTIVE: To assess nutrient intakes and compliance with nutritional recommendations in pregnant women according to selected sociodemographic characteristics and lifestyles. METHODS: Cross-sectional study based on data from Spanish INMA cohort which recruited 2,585 pregnant women between 2003 and 2008 from four different regions of Spain. Sociodemographic information and anthropometry was collected and dietary intake was assessed through Food Frequency Questionnaires. The adequacy of food group intake was assessed considering current recommendations and from the Spanish Society of Nutrition. Moreover, intake of vitamin A, vitamin C and vitamin E, were compared with the Dietary Reference Intakes of the US Institute of Medicine. RESULTS: Percentage of women that did not fulfil the recommendations for cereals and legumes (3-4 servings/day) was 70.0%, for fruit intake (2-3 servings/day) it was 39.2%, for vegetables (2-4 servings/day) 47.3% and for dairy (3-4 servings/day) it was 51.6%. Intake of fruit and vegetables increased with age, educational degree and with physical activity (p<0.05). Also non-Spanish achieved better the recommendations. Percentage of pregnant women that did not fulfil the requirements (DRI) of vitamins A and C was 13.2 % and 16.2 % respectively. More than 65% of the women did not met the recommended diary intake of vitamin E of 19 mg/day during the lactation period. CONCLUSIONS: Maternal age, education, having healthy habits, as well as country of origin are factors strongly associated with the composition of the diet. Sedentary women and those with a low education are at risk for low vitamin and antioxidant intake and non-optimal food choices during pregnancy.
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    ABSTRACT: Background Maternal clinical thyroid disorders can cause reproductive complications. However, the effects of mild thyroid dysfunctions are not yet well established. The aim was to evaluate the association of maternal thyroid function during the first half of pregnancy with birthweight and preterm delivery.Methods We analysed data on 2170 pregnant women and their children from a prospective population-based cohort study in four Spanish areas. Mid-gestation maternal serum and urine samples were gathered to determine thyroid-stimulating hormone (TSH), free thyroxine (fT4), and urinary iodine concentration (UIC). Thyroid status was defined according to percentile distribution as: euthyroid (TSH and fT4 >5th and <95th percentiles); hypothyroxinaemia (fT4 < 5th percentile and TSH normal), hypothyroidism (TSH > 95th percentile and fT4 normal or <5th percentile), hyperthyroxinaemia (fT4 > 95th percentile and TSH normal), and hyperthyroidism (TSH < 5th percentile and fT4 normal or >95th percentile). Response variables were birthweight, small and large for gestational age (SGA/LGA), and preterm delivery.ResultsAn inverse association of fT4 and TSH with birthweight was found, the former remaining when restricted to euthyroid women. High fT4 levels were also associated with an increased risk of SGA [odds ratio, 95% confidence interval (CI) 1.28 (95% CI 1.08, 1.51)]. Mean birthweight was higher in the hypothyroxinaemic group (β = 109, P < 0.01). Iodine intake and UIC were not associated with birth outcomes.Conclusions High maternal fT4 levels during the first half of pregnancy were related to lower birthweight and increased risk of SGA newborns, suggesting that maternal thyroid function may affect fetal growth, even within the normal range.
    Paediatric and Perinatal Epidemiology 02/2015; 29(2). DOI:10.1111/ppe.12172 · 2.81 Impact Factor
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    ABSTRACT: To investigate the risk of lung cancer among cooks, while controlling for smoking habits. We used data from the SYNERGY project including pooled information on lifetime work histories and smoking habits from 16 case-control studies conducted in Europe, Canada, New Zealand, and China. Before adjustment for smoking, we observed an increased risk of lung cancer in male cooks, but not in female cooks. After adjusting, there was no increased risk and no significant exposure-response relationship. Nevertheless, subgroup analyses highlighted some possible excess risks of squamous cell carcinoma and small cell carcinoma in female cooks. There is evidence that lung cancer risks among cooks may be confounded by smoking. After adjustment, cooks did not experience an increased risk of lung cancer overall. The subgroup analyses showing some excess risks among female cooks require cautious interpretation.
    Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine 02/2015; 57(2):202-9. DOI:10.1097/JOM.0000000000000337 · 1.80 Impact Factor
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    ABSTRACT: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.
    Gaceta Sanitaria 01/2015; DOI:10.1016/j.gaceta.2014.12.003 · 1.25 Impact Factor
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    ABSTRACT: Nitrate is a widespread contaminant in drinking water and ingested nitrate under conditions resulting in endogenous nitrosation is suspected to be carcinogenic. However, the suggested association between nitrate in drinking water and bladder cancer remains inconsistent. We evaluated the long-term exposure to drinking water nitrate as a risk factor for bladder cancer, considering endogenous nitrosation modifiers and other covariables. We conducted a hospital-based case-control study of bladder cancer in Spain (1998-2001). Residential histories and water consumption information were ascertained through personal interviews. Historical nitrate levels (1940-2000) were estimated in study municipalities based on monitoring records and water source. Residential histories of study subjects were linked with nitrate estimates by year and municipality to calculate individual exposure from age 18 to recruitment. We calculated odds ratios (OR) and 95% confidence intervals (CI) for bladder cancer among 531 cases and 556 controls with reliable interviews and nitrate exposure information covering at least 70% of years from age 18 to interview. Average residential levels ranged from 2.1mg/L to 12.0mg/L among regions. Adjusted OR (95%CI) for average residential levels relative to ≤5mg/L were 1.2 (0.7-2.0) for >5-10mg/L and 1.1 (0.6-1.9) for >10mg/L. The OR for subjects with longest exposure duration (>20 years) to highest levels (>9.5mg/L) was 1.4 (0.9-2.3). Stratification by intake of vitamin C, vitamin E, meat, and gastric ulcer diagnosis did not modify these results. A non-significant negative association was found with waterborne ingested nitrate with an OR of 0.7 (0.4-1.0) for >8 vs. ≤4mg/day. Adjustment for several covariables showed similar results to crude analyses. Bladder cancer risk was inconsistently associated with chronic exposure to drinking water nitrate at levels below the current regulatory limit. Elevated risk is suggested only among subjects with longest exposure duration to the highest levels. No evidence of interaction with endogenous nitrosation modifiers was observed. Copyright © 2014 Elsevier Inc. All rights reserved.
    Environmental Research 01/2015; 137C:299-307. DOI:10.1016/j.envres.2014.10.034 · 3.95 Impact Factor
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    ABSTRACT: Resumen Introducción y objetivos: El déficit de vitamina D du-rante el embarazo se ha relacionado con sucesos adversos durante la gestación y con el desarrollo infantil postna-tal. En este estudio examinamos los niveles plasmáticos de vitamina D [25(OH)D3] y los factores asociados a su deficiencia e insuficiencia plasmática en embarazadas del norte de España. Material y método: Se han analizado los datos de 453 gestantes participantes en la cohorte INMA-Asturias a las que se determinó la 25(OH)D3 mediante cromatografía líquida de alta resolución. Se ha estimado la ingesta dieté-tica de vitamina D mediante un cuestionario de frecuencia alimentaria validado. Se han estimado las prevalencias de deficiencia [25(OH)D3<20 ng/ml] e insuficiencia [20–29,9 ng/ml] de vitamina D y se ha analizado la distribución de 25(OH)D3 por mes de extracción y otros factores. Resultados: La concentración media de 25(OH)D3 fue 27,7 ng/ml (rango 6,4-69,5). Un 27,4% de gestantes presentaron niveles deficientes y un 35,3% insuficientes. Los niveles de 25(OH)D3 fueron mayores en los meses de verano (mediana 34,1 ng/ml). Hubo un mayor porcenta-je de deficiencia en las gestantes con sobrepeso/obesidad (34,5%) y en las menores de 25 años (47,8%). La inges-ta media diaria de vitamina D fue 5,48 µg/día (DT 2,82 rango 1,09-32,52). Durante los meses de octubre a mayo la ingesta se relacionó con los niveles de 25(OH)D3. Un 8,6% refirieron tomar suplementos de vitamina D. Conclusiones: Se ha detectado una elevada proporción de embarazadas con niveles de vitamina D considerados como deficientes o insuficientes, especialmente en los me-ses de octubre a mayo, en las gestantes con sobrepeso y obesidad y en las de menor edad. Abstract Background and objectives: The vitamin D deficiency during pregnancy has been associated with adverse events during pregnancy and the postnatal child development. In this study we examined plasma levels of vitamin D [25(OH)D3] and factors associated with plasma deficiency and insufficiency in pregnant women in northern Spain. Methods: We analyzed data from 453 pregnant women participating in the INMA-Asturias cohort in which was determined 25(OH)D3 by high resolution liquid chromatography. Dietary intake of vitamin D was estimated through a food frequency validated questionnaire. We estimated the prevalence of deficiency [25(OH)D3 <20 ng / ml] and insufficiency [20 to 29.9 ng / ml] of vitamin D and analyzed the distribution of 25(OH)D3 per month extraction and other factors. Results: The mean concentration of 25(OH)D3 was 27.7 ng/ml (range 6.4 to 69.5). 27.4% of pregnant women had deficient levels and 35.3% inssuficient. Levels of 25(OH)D3 were higher in the summer months (median 34.1 ng/ml). There was a higher percentage of deficiency in pregnant women with overweight/obesity (34.5%) and under 25 years (47.8%). The average daily intake of vitamin D was 5.48 mg / day (SD 2.82 range 1.09 to 32.52). Intake during the months of October to May was associated with levels of 25(OH)D3. 8.6% reported taking supplements of vitamin D. Conclusions: We detected a high proportion of pregnant women with deficient or insufficient vitamin D levels, especially in the months of October to May, in pregnant women with overweight and obesity, and the youngest.
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    ABSTRACT: Abstract DNA methylation changes contribute to bladder carcinogenesis. Trihalomethanes (THM), a class of disinfection by-products, are associated with increased urothelial bladder cancer (UBC) risk. THM exposure in animal models produces DNA hypomethylation. We evaluated the relationship of LINE-1 5-methylcytosine levels (LINE-1%5mC) as outcome of long-term THM exposure among controls and as an effect modifier in the association between THM exposure and UBC risk. We used a case-control study of UBC conducted in Spain. We obtained personal lifetime residential THM levels and measured LINE-1%5mC by pyrosequencing in granulocyte DNA from blood samples in 548 incident cases and 559 hospital controls. Two LINE-1%5mC clusters (above and below 64%) were identified through unsupervised hierarchical cluster analysis. The association between THM levels and LINE-1%5mC was evaluated with beta regression analyses and logistic regression was used to estimate odds ratios (OR) adjusting for covariables. LINE-1%5mC change between percentiles 75(th) and 25(th) of THM levels was 1.8% (95% confidence interval (CI): 0.1, 3.4%) among controls. THM levels above vs. below the median (26 μg/L) were associated with increased UBC risk, OR = 1.86 (95% CI: 1.25, 2.75), overall and among subjects with low levels of LINE-1%5mC (n = 975), OR = 2.14 (95% CI: 1.39, 3.30), but not associated with UBC risk among subjects' high levels of LINE-1%5mC (n = 162), interaction P = 0.03. Results suggest a positive association between LINE-1%5mC and THM levels among controls, and LINE-1%5mC status may modify the association between UBC risk and THM exposure. Because reverse causation and chance cannot be ruled out, confirmation studies are warranted.
    Epigenetics: official journal of the DNA Methylation Society 12/2014; 9(11):1532--1539. DOI:10.4161/15592294.2014.983377 · 5.11 Impact Factor
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    ABSTRACT: Night shift work has been classified as a probable human carcinogen based on experimental studies and limited human evidence on breast cancer. Evidence on other common cancers, such as prostate cancer, is scarce. Chronotype is an individual characteristic that may relate to night work adaptation. We evaluated night shift work with relation to prostate cancer, taking into account chronotype and disease severity in a population based case-control study in Spain. We included 1095 prostate cancer cases and 1388 randomly selected population controls. We collected detailed information on shift schedules (permanent vs rotating, time schedules, duration, frequency), using lifetime occupational history. Socio-demographic and lifestyle factors were assessed by face-to-face interviews and chronotype through a validated questionnaire. We used unconditional logistic regression analysis adjusting for potential confounders. Subjects who had worked at least for one year in night shift work had a slightly higher prostate cancer risk (Odds Ratio (OR) 1.14; 95%CI 0.94, 1.37) compared to never night workers; this risk increased with longer duration of exposure (≥28 years: OR 1.37; 95%CI 1.05, 1.81) (p-trend=0.047). Risks were more pronounced for high risk tumors (D'Amico classification, Relative Risk Ratio (RRR) 1.40; 95%CI 1.05, 1.86), particularly among subjects with longer duration of exposure (≥28 years: RRR 1.63; 95%CI 1.08, 2.45) (p-trend=0.027). Overall risk was higher among subjects with an evening chronotype, but also increased in morning chronotypes after long-term night work. In this large population based study we found an association between night shift work and prostate cancer particularly for tumors with worse prognosis. This article is protected by copyright. All rights reserved.
    International Journal of Cancer 12/2014; DOI:10.1002/ijc.29400 · 5.01 Impact Factor
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    ABSTRACT: Folate intake during pregnancy has been associated with improved neuropsychological development in children, although the effects of high dosages of folic acid (FA) supplements are unclear.
    JAMA Pediatrics 11/2014; 168(11):e142611. DOI:10.1001/jamapediatrics.2014.2611 · 4.25 Impact Factor
  • Epidemiology (Cambridge, Mass.) 11/2014; 25(6):934-935. DOI:10.1097/EDE.0000000000000183 · 6.18 Impact Factor
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    ABSTRACT: A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) ≥ 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 × 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (Ptrend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. Cancer Res; 74(20); 5808-18. ©2014 AACR.
    Cancer Research 10/2014; 74(20):5808-18. DOI:10.1158/0008-5472.CAN-14-1531. · 9.28 Impact Factor
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    ABSTRACT: Background Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks. Objectives In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation. Methods The biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retroviruses (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated. Results A significant sex interaction was observed for AluYb8 (p-value for interaction < 0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p-value < 0.001), while no significant effects were found in girls (p-value = 0.134). Conclusions Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development.
    Environment International 10/2014; 71:81–87. · 5.66 Impact Factor
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    ABSTRACT: To investigate the association of maternal circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration with pregnancy and birth outcomes.
    BJOG An International Journal of Obstetrics & Gynaecology 09/2014; DOI:10.1111/1471-0528.13074 · 3.86 Impact Factor
  • Adonina Tardon
    Medicina Clínica 08/2014; DOI:10.1016/j.medcli.2013.12.004 · 1.25 Impact Factor
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    ABSTRACT: Accumulating evidence from laboratory animal and human studies suggests that air pollution exposure during pregnancy affects cognitive and psychomotor development in childhood.
    Epidemiology (Cambridge, Mass.) 07/2014; DOI:10.1097/EDE.0000000000000133 · 6.18 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
    Human Molecular Genetics 07/2014; DOI:10.1093/hmg/ddu363 · 6.68 Impact Factor
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    ABSTRACT: To build a predictive model for urothelial carcinoma of the bladder (UCB) risk combining both genomic and nongenomic data, 1,127 cases and 1,090 controls from the Spanish Bladder Cancer/EPICURO study were genotyped using the HumanHap 1M SNP array. After quality control filters, genotypes from 475,290 variants were available. Nongenomic information comprised age, gender, region, and smoking status. Three Bayesian threshold models were implemented including: (1) only genomic information, (2) only nongenomic data, and (3) both sources of information. The three models were applied to the whole population, to only nonsmokers, to male smokers, and to extreme phenotypes to potentiate the UCB genetic component. The area under the ROC curve allowed evaluating the predictive ability of each model in a 10-fold cross-validation scenario. Smoking status showed the highest predictive ability of UCB risk (AUCtest = 0.62). On the other hand, the AUC of all genetic variants was poorer (0.53). When the extreme phenotype approach was applied, the predictive ability of the genomic model improved 15%. This study represents a first attempt to build a predictive model for UCB risk combining both genomic and nongenomic data and applying state-of-the-art statistical approaches. However, the lack of genetic relatedness among individuals, the complexity of UCB etiology, as well as a relatively small statistical power, may explain the low predictive ability for UCB risk. The study confirms the difficulty of predicting complex diseases using genetic data, and suggests the limited translational potential of findings from this type of data into public health interventions.
    Genetic Epidemiology 07/2014; 38(5). DOI:10.1002/gepi.21809 · 2.95 Impact Factor

Publication Stats

3k Citations
828.52 Total Impact Points

Institutions

  • 1999–2015
    • University of Oviedo
      • • Department of Medicine
      • • Medicina Preventiva y Salud Pública
      Oviedo, Asturias, Spain
  • 2013
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
  • 2011–2013
    • National Cancer Institute (USA)
      • • Division of Cancer Epidemiology and Genetics
      • • Laboratory of Translational Genomics
      • • Occupational and Environmental Epidemiology
      Maryland, United States
  • 2012
    • University of Murcia
      Murcia, Murcia, Spain
    • Universidad del País Vasco / Euskal Herriko Unibertsitatea
      Leioa, Basque Country, Spain
    • Centro Superior de Investigación en Salud Pública (CSISP)
      Valenza, Valencia, Spain
  • 2007–2011
    • CREAL Center for Research in Environmental Epidemiology
      Barcino, Catalonia, Spain
  • 2006
    • University Pompeu Fabra
      Barcino, Catalonia, Spain
    • Hospital General Universitario de Elche
      Elche, Valencia, Spain
    • IMIM Hospital del Mar Medical Research Institute
      Barcino, Catalonia, Spain
  • 2005
    • Universidad de Jaén
      Jaén, Andalusia, Spain