Paolo Vineis

Imperial College London, Londinium, England, United Kingdom

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Publications (765)4496.57 Total impact

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    ABSTRACT: Long-term exposure to particulate matter (PM) has been associated with increased cardiovascular morbidity and mortality but little is known about the role of the chemical composition of PM. This study examined the association of residential long-term exposure to PM components with incident coronary events. Eleven cohorts from Finland, Sweden, Denmark, Germany, and Italy participated in this analysis. 5,157 incident coronary events were identified within 100,166 persons followed on average for 11.5 years. Long-term residential concentrations of PM < 10 μm (PM10), PM < 2.5 μm (PM2.5), and a priori selected constituents (copper, iron, nickel, potassium, silicon, sulfur, vanadium, and zinc) were estimated with land-use regression models. We used Cox proportional hazard models adjusted for a common set of confounders to estimate cohort-specific component effects with and without including PM mass, and random effects meta-analyses to pool cohort-specific results. A 100 ng/m³ increase in PM10 K and a 50 ng/m³ increase in PM2.5 K were associated with a 6% (hazard ratio and 95% confidence interval: 1.06 [1.01, 1.12]) and 18% (1.18 [1.06, 1.32]) increase in coronary events. Estimates for PM10 Si and PM2.5 Fe were also elevated. All other PM constituents indicated a positive association with coronary events. When additionally adjusting for PM mass, the estimates decreased except for K. This multicenter study of 11 European cohorts pointed to an association between long-term exposure to PM constituents and coronary events, especially for indicators of road dust.
    Epidemiology (Cambridge, Mass.) 05/2015; DOI:10.1097/EDE.0000000000000300 · 6.18 Impact Factor
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    ABSTRACT: The relationship between coffee consumption and coronary heart disease (CHD) has been investigated in several studies with discrepant results. We examined the association between Italian-style (espresso and mocha) coffee consumption and CHD risk. We investigated 12,800 men and 30,449 women without history of cardiovascular disease recruited to the EPICOR prospective cohort study. Coffee consumption was assessed at baseline. In a random sub-cohort of 1472 subjects, plasma triglycerides, and total, LDL and HDL cholesterol were determined to investigate the effect of coffee consumption on plasma lipids. After a mean follow up of 10.9 years, 804 cases of CHD (500 acute events, 56 fatal events and 248 revascularizations, all first events) were identified. Multivariable adjusted hazard ratios for CHD were: 1.18 (95% CI 0.87-1.60) for drinking 1-2 cups/day, 1.37 (95% CI 1.03-1.82) for >2-4 cups/day and 1.52 (95% CI 1.11-2.07) for over 4 cups/day (P trend <0.001) compared to reference (<1 cup/day). Plasma triglycerides, and total, LDL and HDL cholesterol did not vary significantly (ANOVA) with coffee consumption. Consumption of over 2 cups/day of Italian-style coffee is associated with increased CHD risk, but coffee consumption was not associated with plasma lipid changes, so the adverse effect of consumption appears unrelated to lipid profile.
    PLoS ONE 05/2015; 10(5):e0126550. DOI:10.1371/journal.pone.0126550 · 3.53 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 · 5.66 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 · 9.20 Impact Factor
  • International Journal of Cancer 04/2015; DOI:10.1002/ijc.29559. · 5.01 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: journals.permissions@oup.com.
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    ABSTRACT: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause. Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health. We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000. Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale. Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM. Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes. Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ) and Federal Ministry of Education and Research (BMMF) (Germany); Ministry of Health and Social Solidarity, Stavros Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). None of the authors reported a conflict of interest. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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    ABSTRACT: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear. We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures. This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m(2)) (>30), and WC (≥102 cm for men, ≥88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures. Significant interactions (PA × BMI and PA × WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16-30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity. The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health.
    American Journal of Clinical Nutrition 03/2015; 101(3):613-21. DOI:10.3945/ajcn.114.100065 · 6.92 Impact Factor
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    ABSTRACT: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed. We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
    Environmental Health Perspectives 02/2015; DOI:10.1289/ehp.1409149 · 7.03 Impact Factor
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    ABSTRACT: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality. Our aim was to study the association between natural cause mortality and long-term exposure to elemental components of particulate matter. Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori selected components of particulate matter (PM) was characterized following a strictly standardized protocol. Annual average concentrations of Copper (Cu), Iron (Fe), Potassium (K), Nickel (Ni), Sulfur (S), Silicon (Si), Vanadium (V) and Zinc (Zn) within PM size fractions <2.5 µm (PM2.5) and <10 µm (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis. The total study population consisted of 291,816 participants, of which 25,466 died from a natural cause during follow-up (average time of follow-up 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 S (1.14; 95% CI: 1.06, 1.23 per 200 ng/m(3)). In a two-pollutant model, the association with PM2.5 S was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. Long-term exposure to PM2.5 S was associated with natural cause mortality. This association was robust to adjustment for other pollutants and PM2.5.
    Environmental Health Perspectives 02/2015; DOI:10.1289/ehp.1408095 · 7.03 Impact Factor
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    ABSTRACT: Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend<.0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids. These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids.
    PLoS ONE 02/2015; 10(2):e0118206. DOI:10.1371/journal.pone.0118206 · 3.53 Impact Factor
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    ABSTRACT: Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non-type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis. HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers. © 2015 by American Society of Clinical Oncology.
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    ABSTRACT: Alcohol intake has been associated to breast cancer in pre and postmenopausal women; however results are inconclusive regarding tumor hormonal receptor status, and potential modifying factors like age at start drinking. Therefore, we investigated the relation between alcohol intake and the risk of breast cancer using prospective observational data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Up to 334,850 women, aged 35-70 years at baseline, were recruited in ten European countries and followed up an average of 11 years. Alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. The study outcomes were the Hazard ratios (HR) of developing breast cancer according to hormonal receptor status. During 3,670,439 person-years, 11,576 incident breast cancer cases were diagnosed. Alcohol intake was significantly related to breast cancer risk, for each 10g/day increase in alcohol intake the HR increased by 4.2% (95% CI: 2.7%-5.8%). Taking 0 to 5g/day as reference, alcohol intake of >5 to 15g/day was related to a 5.9% increase in breast cancer risk (95% CI: 1%-11%). Significant increasing trends were observed between alcohol intake and ER+/PR+, ER-/PR-, HER2- and ER-/PR-/HER2- tumors. Breast cancer risk was stronger among women who started drinking prior to first full-time pregnancy. Overall, our results confirm the association between alcohol intake and both hormone receptor positive and hormone receptor negative breast tumors, suggesting that timing of exposure to alcohol drinking may affect the risk. Therefore, women should be advised to control their alcohol consumption. This article is protected by copyright. All rights reserved. © 2015 UICC.
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    ABSTRACT: Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval - CI - 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer. This article is protected by copyright. All rights reserved. © 2015 UICC.
  • Paolo Vineis, Rodolfo Saracci
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    ABSTRACT: A conflict of interest arises by having two conflicting goals in one's research. The primary goal of research relevant to public health is to produce impartial evidence on health hazards for humans. Several entities - including industry - may have public health as a goal among others, but this is not their primary goal. Primary goals are in those cases profit or career, that conflict with the goal of health. It is a role of the State to foster research whose primary goal is impartial evidence on factors affecting population health. Disclosure of conflicts of interest is not enough: the view that disclosure solves all problems amounts to say that a declaration of having produced unbiased evidence is a self-fulfilling guarantee that the evidence will not be affected by conflicts of interest. This concept is seriously misleading. A conflict of interest arises from the circumstances in which research occurs and does not exist only in the opinion of some people or groups (or the authors of a paper). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of Epidemiology &amp Community Health 01/2015; DOI:10.1136/jech-2014-205012 · 3.29 Impact Factor
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    ABSTRACT: Background Following wider acceptance of “the thrifty phenotype” hypothesis and the convincing evidence that early life exposures can influence adult health even decades after the exposure, much interest has been placed on the mechanisms through which early life exposures become biologically embedded.Methods In this review, we summarize the current literature regarding biological embedding of early life experiences. To this end we conducted a literature search to identify studies investigating early life exposures in relation to DNA methylation changes. In addition, we summarize the challenges faced in investigations of epigenetic effects, stemming from the peculiarities of this emergent and complex field. A proper systematic review and meta-analyses were not feasible given the nature of the evidence.ResultsWe identified 7 studies on early life socioeconomic circumstances, 10 studies on childhood obesity, and 6 studies on early life nutrition all relating to DNA methylation changes that met the stipulated inclusion criteria. The pool of evidence gathered, albeit small, favours a role of epigenetics and DNA methylation in biological embedding, but replication of findings, multiple comparison corrections, publication bias, and causality are concerns remaining to be addressed in future investigations.Conclusions Based on these results, we hypothesize that epigenetics, in particular DNA methylation, is a plausible mechanism through which early life exposures are biologically embedded. This review describes the current status of the field and acts as a stepping stone for future, better designed investigations on how early life exposures might become biologically embedded through epigenetic effects.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 01/2015; 45(3). DOI:10.1111/eci.12406 · 2.83 Impact Factor
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    ABSTRACT: Several studies have recently identified strong epigenetic signals related to tobacco smoking. However, an aspect that did not receive much attention is the evolution of epigenetic changes with time since smoking cessation. We conducted a series of epigenome wide association studies to capture the dynamics of smoking-induced epigenetic changes after smoking cessation, using genome-wide methylation profiles obtained from blood samples in 745 women from two European populations. Two distinct classes of CpG sites were identified: sites whose methylation reverts to levels typical of never smokers within decades after smoking cessation, and sites remaining differentially methylated, even more than 35 years after smoking cessation. Our results suggest that the dynamics of methylation changes following smoking cessation are driven by a differential and site-specific magnitude of the smoking-induced alterations (with persistent sites being most affected) irrespective of the intensity and duration of smoking. Analyses of the link between methylation and expression levels revealed that methylation predominantly and remotely down-regulates gene expression. Among genes whose expression was associated to our candidate CpG sites, LRRN3 appeared to be particularly interesting as it was one of the few genes whose methylation and expression were directly associated, and the only gene in which both methylation and gene expression were found associated to smoking. Our study highlights persistent epigenetic markers of smoking, which can potentially be detected decades after cessation. Such historical signatures are promising biomarkers to refine individual risk profiling of smoking-induced chronic disease such as lung cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Human Molecular Genetics 01/2015; 24(8). DOI:10.1093/hmg/ddu751 · 6.68 Impact Factor
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    ABSTRACT: Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.
    Nature Communications 01/2015; 6:5751. DOI:10.1038/ncomms6751 · 10.74 Impact Factor
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    ABSTRACT: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend <0.0001), compared to participants with the lowest concordance with the recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall mortality were observed (P for trend 0.004). Meeting the recommendations on body fatness and plant food consumption were associated with improved survival among CRC cases in mutually adjusted models. Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.
    BMC Medicine 01/2015; 13(1):107. DOI:10.1186/s12916-015-0332-5 · 7.28 Impact Factor

Publication Stats

25k Citations
4,496.57 Total Impact Points

Institutions

  • 2005–2015
    • Imperial College London
      • • Department of Epidemiology and Biostatistics
      • • Faculty of Medicine
      Londinium, England, United Kingdom
    • University of New Mexico
      Albuquerque, New Mexico, United States
    • Mario Negri Institute for Pharmacological Research
      • Department of Environmental Health Sciences
      Milano, Lombardy, Italy
  • 1991–2015
    • National Cancer Institute (USA)
      • • Division of Cancer Epidemiology and Genetics
      • • Radiation Epidemiology
      베서스다, Maryland, United States
  • 2014
    • Centre d'Immunologie de Marseille-Luminy
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2011–2014
    • Human Genetics Foundation Torino
      Torino, Piedmont, Italy
    • Change Institute
      Londinium, England, United Kingdom
    • University of Cambridge
      • MRC Epidemiology Unit
      Cambridge, ENG, United Kingdom
    • National Institutes of Health
      • Division of Cancer Epidemiology and Genetics
      Bethesda, MD, United States
    • University of São Paulo
      • Faculdade de Saúde Pública (FSP) (São Paulo)
      Ribeirão Preto, Estado de Sao Paulo, Brazil
  • 2004–2014
    • Utrecht University
      • • Institute for Risk Assessment Sciences (IRAS)
      • • Division of Environmental Epidemiology
      Utrecht, Utrecht, Netherlands
    • Maastricht University
      Maestricht, Limburg, Netherlands
    • Cornell University
      Итак, New York, United States
  • 1982–2014
    • Università degli Studi di Torino
      • • Department of Medical Science
      • • Dipartimento di Biotecnologie Molecolari e Scienze per la Salute
      Torino, Piedmont, Italy
  • 2013
    • Johns Hopkins Medicine
      • Department of Pathology
      Baltimore, Maryland, United States
    • University of Naples Federico II
      • Department of Clinical Medicine and Surgery
      Napoli, Campania, Italy
    • Danish Cancer Society
      København, Capital Region, Denmark
    • Universitätsklinikum Freiburg
      • Center for Chronic Immunodeficiency (CCI)
      Freiburg, Lower Saxony, Germany
  • 2005–2013
    • University Medical Center Utrecht
      • Julius Center for Health Sciences and Primary Care
      Utrecht, Utrecht, Netherlands
  • 2002–2013
    • German Institute of Human Nutrition
      • Department of Epidemiology
      Potsdam, Brandenburg, Germany
  • 2012
    • University of Bristol
      • School of Experimental Psychology
      Bristol, England, United Kingdom
    • Brown University
      • Division of Biology and Medicine
      Providence, RI, United States
    • University of Texas MD Anderson Cancer Center
      • Division of Cancer Prevention & Population Sciences
      Houston, TX, United States
    • Otto-von-Guericke-Universität Magdeburg
      • Institute for Clinical Chemistry and Pathobiochemistry
      Magdeburg, Saxony-Anhalt, Germany
  • 2010–2012
    • University of Oxford
      • • Cancer Epidemiology Unit
      • • Nuffield Department of Clinical Medicine
      Oxford, ENG, United Kingdom
    • Icahn School of Medicine at Mount Sinai
      Borough of Manhattan, New York, United States
    • Radboud University Medical Centre (Radboudumc)
      Nymegen, Gelderland, Netherlands
  • 2008–2012
    • Catalan Institute of Oncology
      • • Nutrition, Environment and Cancer Unit
      • • Cancer Epidemiology Research Programme (PREC)
      • • Translational Research Laboratory
      Badalona, Catalonia, Spain
    • Lund University
      • Department of Occupational and Environmental Medicine
      Lund, Skane, Sweden
  • 1990–2012
    • International Agency for Research on Cancer
      • Nutritional Epidemiology Group
      Lyons, Rhône-Alpes, France
  • 2009–2011
    • National Institute for Public Health and the Environment (RIVM)
      • Centre for Nutrition and Health
      Utrecht, Utrecht, Netherlands
    • IDIBELL Bellvitge Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 2006–2011
    • German Cancer Research Center
      • Division of Cancer Epidemiology
      Heidelberg, Baden-Wuerttemberg, Germany
  • 2003–2011
    • ISI Foundation
      Torino, Piedmont, Italy
  • 2008–2009
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      Milano, Lombardy, Italy
    • Umeå University
      • Department of Surgical and Perioperative Sciences
      Umeå, Västerbotten, Sweden
    • Imperial Valley College
      Imperial, California, United States
  • 2007
    • University of Bergen
      • Institute of Medicine
      Bergen, Hordaland Fylke, Norway
  • 2000–2007
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
    • Memorial Sloan-Kettering Cancer Center
      • Epidemiology & Biostatistics Group
      New York City, NY, United States
  • 1994–2006
    • University of Milan
      Milano, Lombardy, Italy
    • University of Verona
      Verona, Veneto, Italy
  • 2000–2004
    • CRO Centro di Riferimento Oncologico di Aviano
      Aviano, Friuli Venezia Giulia, Italy
  • 2000–2003
    • Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica in Piemonte
      Torino, Piedmont, Italy
  • 1999–2003
    • Ospedale San Giovanni Battista, ACISMOM
      Torino, Piedmont, Italy
    • IMIM Hospital del Mar Medical Research Institute
      Barcino, Catalonia, Spain
    • Regional Environmental Protection Agency, Piedmont, Italy
      Torino, Piedmont, Italy
  • 2001
    • Malmö University
      Malmö, Skåne, Sweden
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
  • 1995
    • University of Antwerp
      Antwerpen, Flemish, Belgium
  • 1992–1995
    • Istituto per lo Studio e la Prevenzione Oncologica (ISPO)
      Florens, Tuscany, Italy
  • 1991–1993
    • University of Cincinnati
      • Department of Environmental Health
      Cincinnati, Ohio, United States
  • 1990–1993
    • Istituto Superiore di Sanità
      Roma, Latium, Italy
  • 1988–1993
    • Rhein Main Medical Center
      Wiesbaden, Hesse, Germany
  • 1989
    • Massachusetts Institute of Technology
      • Division of Toxicology
      Cambridge, Massachusetts, United States