Domenico Palli

National Cancer Institute (USA), 베서스다, Maryland, United States

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Publications (713)4157.23 Total impact

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    ABSTRACT: Colorectal cancer is one of the major causes of cancer mortality world-wide. Prevention would improve if at-risk subjects could be identified. The aim of this study was to characterise plasma protein biomarkers associated with the risk of colorectal cancer in samples collected prospectively, before the disease diagnosis. After an exploratory study on the comprehensive plasma proteome analysis by liquid chromatography-tandem mass spectrometry from ten colorectal cancer cases enrolled at diagnosis, and ten matched controls (Phase 1), a similar preliminary study was performed on prospective plasma samples from ten colorectal cancer cases, enrolled years before disease development, and ten matched controls identified in a nested case-control study within the Florence cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) study (Phase 2); in Phase 3 the validation of the candidate biomarkers by targeted proteomics on 48 colorectal cancer cases and 48 matched controls from the Florence-EPIC cohort, and the evaluation of the disease risk were performed. Systems biology tools indicated that both in the Phase 1 and Phase 2 studies circulating protein levels differing in cases more than 1.5 times from controls, were involved in inflammation and/or immune response. Eight proteins including apolipoprotein C-II, complement C4-B, complement component C9, clusterin, alpha-2-HS-glycoprotein, mannan-binding lectin serine-protease, mannose-binding protein C, and N-acetylmuramoyl-L-alanine amidase were selected as promising candidate biomarkers. Targeted proteomics of the selected proteins in the EPIC samples showed significantly higher clusterin levels in cases than controls, but only in men (mean ± SD, 1.98 ± 0.46 and 1.61 ± 0.43 nmol/mL respectively, Mann-Whitney U, two-tailed P = 0.0173). The remaining proteins were unchanged. Using multivariate logistic models a significant positive association emerged for clusterin, with an 80% increase in the colorectal cancer risk with protein's unit increase, but only in men. The results show that plasma proteins can be altered years before colorectal cancer detection. The high circulating clusterin in pre-diagnostic samples suggests this biomarker can improve the identification of people at risk of colorectal cancer and might help in designing preventive interventions.
    BMC Cancer 12/2015; 15(1):1058. DOI:10.1186/s12885-015-1058-7 · 3.36 Impact Factor
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    ABSTRACT: Background Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. Methods To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. Results A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. Conclusion Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12916-015-0462-9) contains supplementary material, which is available to authorized users.
    BMC Medicine 09/2015; 13. DOI:10.1186/s12916-015-0462-9 · 7.25 Impact Factor
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    ABSTRACT: Acrylamide, classified in 1994 by IARC as 'probably carcinogenic to humans', was discovered in 2002 in some heat-treated, carbohydrate-rich foods. Four prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The purpose of this nested case-control study, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, was to evaluate, for the first time, the association between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) and the risk of developing EC in non-smoking postmenopausal women. Hemoglobin adducts were measured in red blood cells by HPLC/MS/MS. Four exposure variables were evaluated: HbAA, HbGA, their sum (HbAA+HbGA), and their ratio (HbGA/HbAA). The association between hemoglobin adducts and EC was evaluated using unconditional multivariable logistic regression models, and included 383 EC cases (171 were type-I EC), and 385 controls. Exposure variables were analyzed in quintiles based on control distributions. None of the biomarker variables had an effect on overall EC (HRHbAA;Q5vsQ1 : 0.84, 95%CI: 0.49-1.48; HRHbGA;Q5vsQ1 : 0.94, 95%CI: 0.54-1.63) or type-I EC risk. Additionally, none of the subgroups investigated (BMI <25 vs ≥25 kg/m(2) , alcohol drinkers vs never drinkers, oral contraceptive users vs non-users) demonstrated effect measure modification. Hemoglobin adducts of acrylamide or glycidamide were not associated with EC or type-I EC risk in 768 non-smoking postmenopausal women from the EPIC cohort. This article is protected by copyright. All rights reserved.
    International Journal of Cancer 09/2015; DOI:10.1002/ijc.29853 · 5.09 Impact Factor
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    ABSTRACT: There is much evidence supporting the role of telomeres in cancer pathogenesis, however the studies that investigated the association between telomere length and skin cancer risk provided inconsistent results. To help clarify this issue, we performed a systematic review and meta-analysis of published papers on the association between peripheral leukocytes telomere length (PLTL) and the risk of cutaneous melanoma and non-melanoma skin cancer (NMSC). We calculated summary relative risks (SRR) and 95% confidence intervals (95%CI) using random effect models with maximum likelihood estimates, and explored causes of between-studies heterogeneity of risk estimates. We included 1629 cutaneous melanoma and 1439 NMSC from eight independent studies published until March 2015. The SRR of cutaneous melanoma for those in the lowest (vs. highest) category of PLTL distribution was 0.25 (95% CI 0.09-0.67). The results were less clear for NMSC, with two studies reporting no association and one study showing an increase in risk for those in the lowest (vs. highest) category of PLTL distribution. For both cutaneous melanoma and NMSC, the between-studies heterogeneity was large, mainly due to inclusion of hospital-based case-control studies. Our meta-analysis shows evidence of an association between short PLTL and reduced risk for cutaneous melanoma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Journal of dermatological science 08/2015; DOI:10.1016/j.jdermsci.2015.08.003 · 3.42 Impact Factor
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    ABSTRACT: An improved understanding of the contribution of the diet to health and disease risks requires accurate assessments of dietary exposure in nutritional epidemiologic studies. The use of dietary biomarkers may improve the accuracy of estimates. We applied a metabolomic approach in a large cohort study to identify novel biomarkers of intake for a selection of polyphenol-containing foods. The large chemical diversity of polyphenols and their wide distribution over many foods make them ideal biomarker candidates for such foods. Metabolic profiles were measured with the use of high-resolution mass spectrometry in 24-h urine samples from 481 subjects from the large European Prospective Investigation on Cancer and Nutrition cohort. Peak intensities were correlated to acute and habitual dietary intakes of 6 polyphenol-rich foods (coffee, tea, red wine, citrus fruit, apples and pears, and chocolate products) measured with the use of 24-h dietary recalls and food-frequency questionnaires, respectively. Correlation (r > 0.3, p < 0.01 after correction for multiple testing) and discriminant [pcorr (1) > 0.3, VIP > 1.5] analyses showed that >2000 mass spectral features from urine metabolic profiles were significantly associated with the consumption of the 6 selected foods. More than 80 polyphenol metabolites associated with the consumption of the selected foods could be identified, and large differences in their concentrations reflecting individual food intakes were observed within and between 4 European countries. Receiver operating characteristic curves showed that 5 polyphenol metabolites, which are characteristic of 5 of the 6 selected foods, had a high predicting ability of food intake. Highly diverse food-derived metabolites (the so-called food metabolome) can be characterized in human biospecimens through this powerful metabolomic approach and screened to identify novel biomarkers for dietary exposures, which are ultimately essential to better understand the role of the diet in the cause of chronic diseases. © 2015 American Society for Nutrition.
    American Journal of Clinical Nutrition 08/2015; DOI:10.3945/ajcn.114.101881 · 6.77 Impact Factor
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    ABSTRACT: Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation. In EPIC, we found that high epigenome-wide methylation was associated with lower risk of breast cancer (odds ratio (OR) per 1 SD = 0.61, 95 % confidence interval (CI) 0.47-0.80; -0.2 % average difference in epigenome-wide methylation for cases and controls). Specifically, this was observed in gene bodies (OR = 0.51, 95 % CI 0.38-0.69) but not in gene promoters (OR = 0.92, 95 % CI 0.64-1.32). The association was not replicated in NOWAC (OR = 1.03 95 % CI 0.81-1.30). The reasons for heterogeneity across studies are unclear. However, data from the BGS cohort was consistent with epigenome-wide hypomethylation in breast cancer cases across the overlapping 450k probe sites (difference in average epigenome-wide methylation in case and control DNA pools = -0.2 %). We conclude that epigenome-wide hypomethylation of DNA from pre-diagnostic blood samples may be predictive of breast cancer risk and may thus be useful as a clinical biomarker.
    08/2015; 7(1):67. DOI:10.1186/s13148-015-0104-2
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    ABSTRACT: Increasing evidence indicates that common genetic variants may contribute to the heritable risk of breast cancer (BC). In this study, we investigated whether single nucleotide polymorphisms (SNPs), within the 8q24.21 multi-cancer susceptibility region and within BC-associated loci widespread in the genome, may influence the risk of BC in men, and whether they may be associated with specific clinical-pathologic characteristics of male BC (MBC). In the frame of the ongoing Italian Multicenter Study on MBC, we performed a case-control study on 386 MBC cases, including 50 BRCA1/2 mutation carriers, and 1105 healthy male controls, including 197 unaffected BRCA1/2 mutation carriers. All 1491 subjects were genotyped by Sequenom iPLEX technology for a total of 29 susceptibility SNPs. By logistic regression models, we found a significant association with MBC risk for five SNPs: rs1562430 (p=0.002) and rs445114 (p=0.026) both within the 8q24.21 region; rs1011970/9p21.3 (p=0.011), rs614367/11q13.3 (p=0.016) and rs1314913/14q24.1 (p<0.0001). Differences in the distribution of rs614367/11q13.3 genotypes according to oestrogen receptor (ER) status (p=0.006), and of rs1011970/9p21.3 genotypes according to human epidermal growth factor receptor 2 (HER2) status (p=0.002) emerged. Association of rs1011970/9p21.3 risk genotype with HER2+MBC was confirmed by a multivariate analysis. rs1314913/14q24.1 was associated with increased MBC risk in analyses restricted to male BRCA1/2 mutation carriers (p=0.041). In conclusion, we provided the first evidence that the 8q24.21 region is associated with MBC risk. Furthermore, we showed that the SNPs rs1562430/8q24.21 and rs1314913/14q24.1 strongly influence BC risk in men and suggested that the SNP rs1314913/14q24.1 may act as a risk modifier locus in male BRCA1/2 mutation carriers. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European journal of cancer (Oxford, England: 1990) 08/2015; DOI:10.1016/j.ejca.2015.07.020 · 5.42 Impact Factor
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    ABSTRACT: The crosstalk between microRNAs (miRNAs) and other epigenetic factors may lead to novel hypotheses about carcinogenesis identifying new targets for research. Since a single miRNA can regulate multiple downstream target genes, its altered expression may potentially be a sensitive biomarker to detect early malignant transformation and improve diagnosis and prognosis. In the current study, we tested the hypothesis that altered methylation of miRNA encoding genes, associated with deregulated mature miRNA expression, may be related to dietary and lifestyle factors and may contribute to cancer development.In a case-control study nested in a prospective cohort (EPIC-Italy), we analysed DNA methylation levels of miRNA encoding genes (2,191 CpG probes related to 517 genes) that are present in the Infinium Human Methylation450 BeadChip array in prediagnostic peripheral white blood cells of subjects who developed Colorectal Cancer (CRC, n=159) or Breast Cancer (BC, n=166) and matched subjects who remained clinically healthy.In the whole cohort, several differentially methylated miRNA genes were observed in association with age, sex, smoking habits and physical activity. Interestingly, in the case-control study, 8 differentially methylated miRNAs were identified in subjects who went on to develop BC (miR-328, miR-675, miR-1307, miR-1286, miR-1275, miR-1910, miR-24-1, and miR-548a-1; all Bonferroni-adjusted p-values < 0.05). No significant associations were found with CRC.Assuming that altered methylation of miRNAs detectable in blood may be present before diagnosis, it may represent a biomarker for early detection or risk of cancer and may help to understand the cascade of events preceding tumour onset. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email:
    Carcinogenesis 07/2015; 75(15 Supplement). DOI:10.1093/carcin/bgv102 · 5.33 Impact Factor
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    ABSTRACT: Metabolomics is a potentially powerful tool for identification of biomarkers associated with lifestyle exposures and risk of various diseases. This is the rationale of the 'meeting-in-the-middle' concept, for which an analytical framework was developed in this study. In a nested case-control study on hepatocellular carcinoma (HCC) within the European Prospective Investigation into Cancer and nutrition (EPIC), serum (1)H nuclear magnetic resonance (NMR) spectra (800 MHz) were acquired for 114 cases and 222 matched controls. Through partial least square (PLS) analysis, 21 lifestyle variables (the 'predictors', including information on diet, anthropometry and clinical characteristics) were linked to a set of 285 metabolic variables (the 'responses'). The three resulting scores were related to HCC risk by means of conditional logistic regressions. The first PLS factor was not associated with HCC risk. The second PLS metabolomic factor was positively associated with tyrosine and glucose, and was related to a significantly increased HCC risk with OR = 1.11 (95% CI: 1.02, 1.22, P = 0.02) for a 1SD change in the responses score, and a similar association was found for the corresponding lifestyle component of the factor. The third PLS lifestyle factor was associated with lifetime alcohol consumption, hepatitis and smoking, and had negative loadings on vegetables intake. Its metabolomic counterpart displayed positive loadings on ethanol, glutamate and phenylalanine. These factors were positively and statistically significantly associated with HCC risk, with 1.37 (1.05, 1.79, P = 0.02) and 1.22 (1.04, 1.44, P = 0.01), respectively. Evidence of mediation was found in both the second and third PLS factors, where the metabolomic signals mediated the relation between the lifestyle component and HCC outcome. This study devised a way to bridge lifestyle variables to HCC risk through NMR metabolomics data. This implementation of the 'meeting-in-the-middle' approach finds natural applications in settings characterised by high-dimensional data, increasingly frequent in the omics generation. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail:
    Mutagenesis 06/2015; DOI:10.1093/mutage/gev045 · 2.79 Impact Factor
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    Dataset: IJC2015
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    ABSTRACT: Polyphenols are plant secondary metabolites with a large variability in their chemical structure and dietary occurrence that have been associated with some protective effects against several chronic diseases. To date, limited data exist on intake of polyphenols in populations. The current cross-sectional analysis aimed at estimating dietary intakes of all currently known individual polyphenols and total intake per class and subclass, and to identify their main food sources in the European Prospective Investigation into Cancer and Nutrition cohort. Dietary data at baseline were collected using a standardized 24-h dietary recall software administered to 36,037 adult subjects. Dietary data were linked with Phenol-Explorer, a database with data on 502 individual polyphenols in 452 foods and data on polyphenol losses due to cooking and food processing. Mean total polyphenol intake was the highest in Aarhus-Denmark (1786 mg/day in men and 1626 mg/day in women) and the lowest in Greece (744 mg/day in men and 584 mg/day in women). When dividing the subjects into three regions, the highest intake of total polyphenols was observed in the UK health-conscious group, followed by non-Mediterranean (non-MED) and MED countries. The main polyphenol contributors were phenolic acids (52.5-56.9 %), except in men from MED countries and in the UK health-conscious group where they were flavonoids (49.1-61.7 %). Coffee, tea, and fruits were the most important food sources of total polyphenols. A total of 437 different individual polyphenols were consumed, including 94 consumed at a level >1 mg/day. The most abundant ones were the caffeoylquinic acids and the proanthocyanidin oligomers and polymers. This study describes the large number of dietary individual polyphenols consumed and the high variability of their intakes between European populations, particularly between MED and non-MED countries.
    European Journal of Nutrition 06/2015; DOI:10.1007/s00394-015-0950-x · 3.47 Impact Factor
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    ABSTRACT: Aims/hypothesis: Intake of dietary fibre has been associated with a reduced risk of type 2 diabetes, but few European studies have been published on this. We evaluated the association between intake of dietary fibre and type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study and in a meta-analysis of prospective studies. Methods: During 10.8 years of follow-up, 11,559 participants with type 2 diabetes were identified and a subcohort of 15,258 participants was selected for the case-cohort study. Country-specific HRs were estimated using Prentice-weighted Cox proportional hazards models and were pooled using a random effects meta-analysis. Eighteen other cohort studies were identified for the meta-analysis. Results: In the EPIC-InterAct Study, dietary fibre intake was associated with a lower risk of diabetes (HRQ4 vs Q1 0.82; 95% CI 0.69, 0.97) after adjustment for lifestyle and dietary factors. Similar inverse associations were observed for the intake of cereal fibre and vegetable fibre, but not fruit fibre. The associations were attenuated and no longer statistically significant after adjustment for BMI. In the meta-analysis (19 cohorts), the summary RRs per 10 g/day increase in intake were 0.91 (95% CI 0.87, 0.96) for total fibre, 0.75 (95% CI 0.65, 0.86) for cereal fibre, 0.95 (95% CI 0.87, 1.03) for fruit fibre and 0.93 (95% CI 0.82, 1.05) for vegetable fibre. Conclusions/interpretation: The overall evidence indicates that the intake of total and cereal fibre is inversely related to the risk of type 2 diabetes. The results of the EPIC-InterAct Study suggest that the association may be partially explained by body weight.
    Diabetologia 05/2015; 58(7):1394-1408. DOI:10.1007/s00125-015-3585-9 · 6.67 Impact Factor
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    ABSTRACT: Endometrial cancer (EC) is the fourth most frequent cancer in women in Europe, and as its incidence is increasing, prevention strategies gain further pertinence. Risk prediction models can be a useful tool for identifying women likely to benefit from targeted prevention measures. On the basis of data from 201,811 women (mostly aged 30-65 years) including 855 incident EC cases from eight countries in the European Prospective Investigation into Cancer and Nutrition cohort, a model to predict EC was developed. A step-wise model selection process was used to select confirmed predictive epidemiologic risk factors. Piece-wise constant hazard rates in 5-year age-intervals were estimated in a cause-specific competing risks model, five-fold-cross-validation was applied for internal validation. Risk factors included in the risk prediction model were body-mass index (BMI), menopausal status, age at menarche and at menopause, oral contraceptive use, overall and by different BMI categories and overall duration of use, parity, age at first full-term pregnancy, duration of menopausal hormone therapy and smoking status (specific for pre, peri- and post-menopausal women). These variables improved the discriminating capacity to predict risk over 5 years from 71 % for a model based on age alone to 77 % (overall C statistic), and the model was well-calibrated (ratio of expected to observed cases = 0.99). Our model could be used for the identification of women at increased risk of EC in Western Europe. To achieve an EC-risk model with general validity, a large-scale cohort-consortium approach would be needed to assess and adjust for population variation.
    European Journal of Epidemiology 05/2015; DOI:10.1007/s10654-015-0030-9 · 5.34 Impact Factor
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    ABSTRACT: To test whether the inflammatory potential of diet, as measured using the dietary inflammatory index (DII), is associated with risk of lung cancer or other respiratory conditions and to compare results obtained with those based on the aMED score, an established dietary index that measures adherence to the traditional Mediterranean diet. In 4336 heavy smokers enrolled in a prospective, non-randomized lung cancer screening program, we measured participants' diets at baseline using a self-administered food frequency questionnaire from which dietary scores were calculated. Cox proportional hazards and logistic regression models were used to assess association between the dietary indices and lung cancer diagnosed during annual screening, and other respiratory outcomes that were recorded at baseline, respectively. In multivariable analysis, adjusted for baseline lung cancer risk (estimated from age, sex, smoking history, and asbestos exposure) and total energy, both DII and aMED scores were associated with dyspnoea (p trend = 0.046 and 0.02, respectively) and radiological evidence of emphysema (p trend = 0.0002 and 0.02). After mutual adjustment of the two dietary scores, only the association between DII and radiological evidence of emphysema (Q4 vs. Q1, OR 1.30, 95 % CI 1.01-1.67, p trend = 0.012) remained statistically significant. At univariate analysis, both DII and aMED were associated with lung cancer risk, but in fully adjusted multivariate analysis, only the association with aMED remained statistically significant (p trend = 0.04). Among heavy smokers, a pro-inflammatory diet, as indicated by increasing DII score, is associated with dyspnoea and radiological evidence of emphysema. A traditional Mediterranean diet, which is associated with a lower DII, may lower lung cancer risk.
    European Journal of Nutrition 05/2015; DOI:10.1007/s00394-015-0920-3 · 3.47 Impact Factor
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    ABSTRACT: We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid associated loci. We used data of the EPIC-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries. During a mean (SD) follow-up of 10 (4) years, 10,576 verified incident type 2 diabetes cases were ascertained. Higher uric acid associated with higher diabetes risk following adjustment for confounders, with a HR of 1.20 (95%CI: 1.11,1.30) per 59.48 micromol/L (1 mg/dL) uric acid. The genetic score raised uric acid by 17 micromol/L (95%CI: 15,18) per SD increase, and explained 4% of uric acid variation. Using the genetic score to estimate the unconfounded effect found that a 59.48 micromol/L higher uric acid concentration did not have a causal effect on diabetes (HR 1.01, 95%CI: 0.87,1.16). Including data from DIAGRAM consortium, increasing our dataset to 41,508 diabetes cases, the summary OR estimate was 0.99 (95%CI: 0.92, 1.06). In conclusion, our study does not support a causal effect of circulating uric acid on diabetes risk. Uric acid lowering therapies may therefore not be beneficial in reducing diabetes risk.
    Diabetes 04/2015; 64(8). DOI:10.2337/db14-0742 · 8.10 Impact Factor
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    ABSTRACT: Long-term exposure to ambient air pollution can lead to chronic health effects such as cancer, cardiovascular and respiratory disease. Systemic inflammation has been hypothesized as a putative biological mechanism contributing to these adverse health effects. We evaluated the effect of long-term exposure to air pollution on blood markers of systemic inflammation. We measured a panel of 28 inflammatory markers in peripheral blood samples from 587 individuals that were biobanked as part of a prospective study. Participants were from Varese and Turin (Italy) and Umea (Sweden). Long-term air pollution estimates of nitrogen oxides (NOx) were available from the European Study of Cohorts for Air Pollution Effects (ESCAPE). Linear mixed models adjusted for potential confounders were applied to assess the association between NOx and the markers of inflammation. Long-term exposure to NOx was associated with decreased levels of interleukin (IL)-2, IL-8, IL-10 and tumor necrosis factor-α in Italy, but not in Sweden. NOx exposure levels were considerably lower in Sweden than in Italy (Sweden: median (5th, 95th percentiles) 6.65μg/m(3) (4.8, 19.7); Italy: median (5th, 95th percentiles) 94.2μg/m(3) (7.8, 124.5)). Combining data from Italy and Sweden we only observed a significant association between long-term exposure to NOx and decreased levels of circulating IL-8. We observed some indication for perturbations in the inflammatory markers due to long-term exposure to NOx. Effects were stronger in Italy than in Sweden, potentially reflecting the difference in air pollution levels between the two cohorts. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Environment international 04/2015; 81:1-7. DOI:10.1016/j.envint.2015.04.003 · 5.56 Impact Factor
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    ABSTRACT: In humans, low socioeconomic status (SES) across the life course is associated with greater diurnal cortisol production, increased inflammatory activity and higher circulating antibodies for several pathogens, all suggesting a dampened immune response. Recent evidence suggests that DNA methylation of pro-inflammatory genes may be implicated in the biological embedding of the social environment. The present study examines the association between life-course SES and DNA methylation of candidate genes, selected on the basis of their involvement in SES-related inflammation, in the context of a genome-wide methylation study. Participants were 857 healthy individuals sampled from the EPIC Italy prospective cohort study. Indicators of SES were associated with DNA methylation of genes involved in inflammation. NFATC1, in particular, was consistently found to be less methylated in individuals with low vs high SES, in a dose-dependent manner. IL1A, GPR132 and genes belonging to the MAPK family were also less methylated among individuals with low SES. In addition, associations were found between SES and CXCL2 and PTGS2, but these genes were consistently more methylated among low SES individuals. Our findings support the hypothesis that the social environment leaves an epigenetic signature in cells. Although the functional significance of SES-related DNA methylation is still unclear, we hypothesize that it may link SES to chronic disease risk. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
    International Journal of Epidemiology 04/2015; DOI:10.1093/ije/dyv060 · 9.18 Impact Factor
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    ABSTRACT: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P difference = .87) and after excluding case patients diagnosed within the first four follow-up years. These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
    JNCI Journal of the National Cancer Institute 04/2015; 107(4). DOI:10.1093/jnci/djv010 · 12.58 Impact Factor
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    ABSTRACT: Thyroid cancer has a higher incidence in women than in men, and it has been hypothesized that hormonal factors may explain such disparity. We performed a meta-analysis of observational prospective studies to investigate the association between menstrual and reproductive variables and exogenous hormone use and the risk of thyroid cancer among women. We calculated summary relative risks and 95 % confidence intervals (95 % CI) using random effect models. Overall, 5,434 thyroid cancer cases from twenty-four papers were included. Increasing age at first pregnancy/birth (SRR 1.56, 95 % CI 1.01-2.42) and hysterectomy (SRR 1.43, 95 % CI 1.15-1.78) were associated with thyroid cancer risk. Women that were in menopause at enrolment had a reduced thyroid cancer risk (SRR 0.79, 95 % CI 0.62-1.01). No other menstrual, reproductive, and hormonal variable was associated with thyroid cancer risk. Menstrual and reproductive factors may play a role in the etiology of thyroid cancer, possibly through the mediation of estrogen receptors.
    Cancer Causes and Control 03/2015; 26(4). DOI:10.1007/s10552-015-0546-z · 2.74 Impact Factor

Publication Stats

21k Citations
4,157.23 Total Impact Points


  • 2015
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      베서스다, Maryland, United States
  • 2008–2015
    • Breast Cancer Prevention Institute
      Сомерсвилл, New Jersey, United States
    • Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica in Piemonte
      Torino, Piedmont, Italy
  • 1986–2015
    • Istituto per lo Studio e la Prevenzione Oncologica (ISPO)
      Florens, Tuscany, Italy
  • 2014
    • Centre d'Immunologie de Marseille-Luminy
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2010–2014
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Berlín, Berlin, Germany
    • Icahn School of Medicine at Mount Sinai
      • Institute for Translational Epidemiology
      Borough of Manhattan, New York, United States
  • 2013
    • University Medical Center Utrecht
      • Department of Gastroenterology and Hepatology
      Utrecht, Utrecht, Netherlands
  • 2012
    • Catalan Institute of Oncology
      • Nutrition, Environment and Cancer Unit
      Badalona, Catalonia, Spain
  • 2009–2012
    • University of Oxford
      • Cancer Epidemiology Unit
      Oxford, ENG, United Kingdom
    • Istituto Superiore di Sanità
      • Department of Environment and Primary Prevention
      Roma, Latium, Italy
  • 2011
    • International Agency for Research on Cancer
      Lyons, Rhône-Alpes, France
    • Malmö University
      Malmö, Skåne, Sweden
  • 1991–2009
    • University of Florence
      • Dipartimento di Scienze Biomediche, Sperimentali e Cliniche
      Florens, Tuscany, Italy
  • 2007
    • Umeå University
      Umeå, Västerbotten, Sweden
    • National Centre for Oncological Treatment (Italy)
      Ticinum, Lombardy, Italy
  • 2002–2007
    • University of Naples Federico II
      • Section of Psychology
      Napoli, Campania, Italy
  • 2006
    • Istituto Toscano Tumori
      Florens, Tuscany, Italy
    • Universitetet i Tromsø
      • Department of Community Medicine
      Tromsø, Troms Fylke, Norway
  • 2005
    • Imperial College London
      • Department of Epidemiology and Biostatistics
      London, ENG, United Kingdom
  • 2003
    • Università degli Studi di Roma "La Sapienza"
      • Laboratory of Experimental Medicine and Pathology Environmental
      Roma, Latium, Italy
  • 1989–2001
    • Mario Negri Institute for Pharmacological Research
      • • Laboratory of Molecular Toxicology
      • • Department of Epidemiology
      Milano, Lombardy, Italy
  • 2000
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      Chieta, Abruzzo, Italy
  • 1999
    • University of Bologna
      • Department of Medical and Surgical Sciences DIMEC
      Bolonia, Emilia-Romagna, Italy
  • 1998
    • Azienda Ospedaliera Santa Maria Nuova di Reggio Emilia
      Reggio nell'Emilia, Emilia-Romagna, Italy
    • NCI-Frederick
      Maryland, United States
  • 1997
    • Sant´Andrea Hospital
      Roma, Latium, Italy
  • 1994
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      Meldola, Emilia-Romagna, Italy
  • 1988
    • CRO Centro di Riferimento Oncologico di Aviano
      • Division of Medical Oncology A
      Aviano, Friuli Venezia Giulia, Italy