Publications by authors named "Paolo Vineis"

760 Publications

Exposure to widespread drinking water chemicals, blood inflammation markers, and colorectal cancer.

Environ Int 2021 Sep 17;157:106873. Epub 2021 Sep 17.

ISGlobal, Barcelona, Spain; CIBER epidemiología y salud pública (CIBERESP), Madrid, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.

Background: Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water associated with colorectal cancer risk but mechanisms are not well understood.

Objectives: We explored the association between exposure to THMs and nitrate in drinking water and inflammation markers, and the link with colorectal cancer risk.

Methods: A subset of 198 colorectal cancer cases and 205 controls from the multicase-control study MCC-Spain were included. Average concentration of THMs (chloroform, bromodichloromethane, dibromochloromethane, bromoform) and nitrate in tap water at the residence was estimated from age 18 until 2 years before the interview ("long term") and for a recent period (3 years before diagnosis). Serum levels of EGF, eotaxin, G-CSF, IL-17E, IL-1rA, IL-8, IP-10, MDC, MPO, periostin, VEGF, and C-reactive protein (CRP) were measured. We estimated the linear association between inflammation markers and exposure among controls, and the odds ratio of colorectal cancer associated with THM and nitrate exposure, and inflammation markers. A mediation analysis was conducted to identify inflammation markers in the pathway between THM/nitrate exposure and colorectal cancer.

Results: Serum concentrations of EGF, IL-8, IL-17E and eotaxin increased with recent residential levels of brominated THMs, chloroforom and/or total THM. No associations were observed for nitrate and for long-term residential THM levels. All residential exposures except chloroform were positively associated with colorectal cancer. Serum concentrations of VEGF and periostin were positively associated with colorectal cancer, while EGF was inversely associated. One protein-exposure combination (periostin-recent ingested brominated THMs) slightly mediated the association with colorectal cancer risk.

Discussion: Results suggest that estimated THM exposure is involved in inflammation processes. However, the study design was limited to stablish etiologically relevant associations between the protein levels and colorectal cancer risk. The lack of association between nitrate exposure and inflammation markers suggests other biological mechanisms are involved in the link with colorectal cancer.
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http://dx.doi.org/10.1016/j.envint.2021.106873DOI Listing
September 2021

Consumption of ultra-processed foods associated with weight gain and obesity in adults: A multi-national cohort study.

Clin Nutr 2021 Sep 21;40(9):5079-5088. Epub 2021 Aug 21.

Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Background: There is a worldwide shift towards increased consumption of ultra-processed foods (UPF) with concurrent rising prevalence of obesity. We examined the relationship between the consumption of UPF and weight gain and risk of obesity.

Methods: This prospective cohort included 348 748 men and women aged 25-70 years. Participants were recruited between 1992 and 2000 from 9 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Two body weight measures were available, at baseline and after a median follow-up time of 5 years. Foods and drinks were assessed at baseline by dietary questionnaires and classified according to their degree of processing using NOVA classification. Multilevel mixed linear regression was used to estimate the association between UPF consumption and body weight change (kg/5 years). To estimate the relative risk of becoming overweight or obese after 5 years we used Poisson regression stratified according to baseline body mass index (BMI).

Results: After multivariable adjustment, higher UPF consumption (per 1 SD increment) was positively associated with weight gain (0·12 kg/5 years, 95% CI 0·09 to 0·15). Comparing highest vs. lowest quintile of UPF consumption was associated with a 15% greater risk (95% CI 1·11, 1·19) of becoming overweight or obese in normal weight participants, and with a 16% greater risk (95% CI 1·09, 1·23) of becoming obese in participants who were overweight at baseline.

Conclusions: These results are supportive of public health campaigns to substitute UPF for less processed alternatives for obesity prevention and weight management.
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http://dx.doi.org/10.1016/j.clnu.2021.08.009DOI Listing
September 2021

Seroprevalence of SARS-CoV-2 Among Workers in Northern Italy.

Ann Work Expo Health 2021 Aug 8. Epub 2021 Aug 8.

Department of Translation Medicine, Università del Piemonte Orientale, Via Solaroli 17 Novara, 20100, Italy.

Background: The spread of severe acute respiratory coronavirus 2 (SARS-CoV-2) among active workers is poor known. The aim of our study was to evaluate the seroprevalence of immunoglobulin G (IgG) among a convenience sample of workers and to identify high-risk job sectors during the first pandemic way.

Methods: We conducted a cross-sectional study among workers tested for SARS-CoV-2 between 28 March and 7 August 2020, recorded by a private healthcare center located in North-West Italy. Association among seroprevalence and demographic and occupational variables was evaluated using chi square test and the seroprevalence and 95% confidence intervals (CI) were calculated.

Results: We collected the results for 23568 serological tests from a sample of 22708 workers from about 1000 companies. Median age was 45 years and about 60% of subjects were male. The overall seroprevalence was 4.97% [95%CI 4.69-5.25]. No statistical difference was found among gender while seroprevalence was associated with subjects' age, geographical location, and occupational sector. Significantly higher values of positivity were observed for the logistics sector (31.3%), weaving factory (12.6%), nursing homes (9.8%), and chemical industry (6.9%) workers. However, we observed some clusters of cases in single companies independently from the sector.Then, a detailed focus on 940 food workers shown a seroprevalence of 5.21% [95%CI 3.79-6.63] and subjects who self-reported COVID-19 symptoms and who worked during lockdown had a higher probability of being infected (p < 0.001).

Conclusions: Data obtained might be useful for future public health decision; more than occupation sector, it seems that failure on prevention system in single companies increase the SARS-CoV-2 transmission.
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http://dx.doi.org/10.1093/annweh/wxab062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385866PMC
August 2021

Inflammation-Related Marker Profiling of Dietary Patterns and All-cause Mortality in the Melbourne Collaborative Cohort Study.

J Nutr 2021 Jul 28. Epub 2021 Jul 28.

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

Background: Nutritional epidemiology research using self-reported dietary intake is prone to measurement error. Objective methods are being explored to overcome this limitation.

Objectives: We aimed to examine 1) the association between plasma markers related to inflammation and derive marker scores for dietary patterns [Mediterranean dietary score (MDS), energy-adjusted Dietary Inflammatory Index (E-DIITM), Alternative Healthy Eating Index 2010 (AHEI)] and 2) the associations of these marker scores with mortality.

Methods: Weighted marker scores were derived from the cross-sectional association between 30 plasma markers and each dietary score (assessed using food-frequency questionnaires) using linear regression for 770 participants in the Melbourne Collaborative Cohort Study (aged 50-82 y). Prospective associations between marker scores and mortality (n = 249 deaths) were assessed using Cox regression (median follow-up: 14.4 y).

Results: The MDS, E-DII, and AHEI were associated (P < 0.05) with 9, 14, and 11 plasma markers, respectively. Healthier diets (higher MDS and AHEI, and lower anti-inflammatory, E-DII) were associated with lower concentrations of kynurenines, neopterin, IFN-γ, cytokines, and C-reactive protein. Five of 6 markers common to the 3 dietary scores were components of the kynurenine pathway. The 3 dietary-based marker scores were highly correlated (Spearman ρ: -0.74, -0.82, and 0.93). Inverse associations (for 1-SD increment) were observed with all-cause mortality for the MDS marker score (HR: 0.84; 95% CI: 0.72-0.98) and the AHEI marker score (HR: 0.76; 95% CI: 0.66-0.89), whereas a positive association was observed with the E-DII marker score (HR: 1.18; 95% CI: 1.01-1.39). The same magnitude of effect was not observed for the respective dietary patterns.

Conclusions: Markers involved in inflammation-related processes are associated with dietary quality, including a substantial overlap between markers associated with the MDS, the E-DII, and the AHEI, especially kynurenines. Unfavorable marker scores, reflecting poorer-quality diets, were associated with increased mortality.
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http://dx.doi.org/10.1093/jn/nxab231DOI Listing
July 2021

Transdisciplinary research and clinical priorities for better health.

PLoS Med 2021 Jul 27;18(7):e1003699. Epub 2021 Jul 27.

Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.

Modern medicine makes it possible for many people to live with multiple chronic diseases for decades, but this has enormous social, financial, and environmental consequences. Preclinical, epidemiological, and clinical trial data have shown that many of the most common chronic diseases are largely preventable with nutritional and lifestyle interventions that are targeting well-characterized signaling pathways and the symbiotic relationship with our microbiome. Most of the research priorities and spending for health are focused on finding new molecular targets for the development of biotech and pharmaceutical products. Very little is invested in mechanism-based preventive science, medicine, and education. We believe that overly enthusiastic expectations regarding the benefits of pharmacological research for disease treatment have the potential to impact and distort not only medical research and practice but also environmental health and sustainable economic growth. Transitioning from a primarily disease-centered medical system to a balanced preventive and personalized treatment healthcare system is key to reduce social disparities in health and achieve financially sustainable, universal health coverage for all. In this Perspective article, we discuss a range of science-based strategies, policies, and structural reforms to design an entire new disease prevention-centered science, educational, and healthcare system that maximizes both human and environmental health.
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http://dx.doi.org/10.1371/journal.pmed.1003699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315511PMC
July 2021

Plasma concentrations of persistent organic pollutants and pancreatic cancer risk.

Int J Epidemiol 2021 Jul 14. Epub 2021 Jul 14.

Cancer Registry and Histopathology Department, "Civic-M.P. Arezzo" Hospital, ASP Ragusa, Ragusa, Italy.

Background: Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts.

Methods: We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline.

Results: Some associations were observed at higher concentrations of p, p'-DDT, trans-nonachlor, β-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95% confidence interval 1.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted >6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted >6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk.

Conclusions: Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.
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http://dx.doi.org/10.1093/ije/dyab115DOI Listing
July 2021

Cord blood metabolic signatures predictive of childhood overweight and rapid growth.

Int J Obes (Lond) 2021 Jul 12. Epub 2021 Jul 12.

Μedical Research Council Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.

Introduction: Metabolomics may identify biological pathways predisposing children to the risk of overweight and obesity. In this study, we have investigated the cord blood metabolic signatures of rapid growth in infancy and overweight in early childhood in four European birth cohorts.

Methods: Untargeted liquid chromatography-mass spectrometry metabolomic profiles were measured in cord blood from 399 newborns from four European cohorts (ENVIRONAGE, Rhea, INMA and Piccolipiu). Rapid growth in the first year of life and overweight in childhood was defined with reference to WHO growth charts. Metabolome-wide association scans for rapid growth and overweight on over 4500 metabolic features were performed using multiple adjusted logistic mixed-effect models and controlling the false discovery rate (FDR) at 5%. In addition, we performed a look-up analysis of 43 pre-annotated metabolites, previously associated with birthweight or rapid growth.

Results: In the Metabolome-Wide Association Study analysis, we identified three and eight metabolites associated with rapid growth and overweight, respectively, after FDR correction. Higher levels of cholestenone, a cholesterol derivative produced by microbial catabolism, were predictive of rapid growth (p = 1.6 × 10). Lower levels of the branched-chain amino acid (BCAA) valine (p = 8.6 × 10) were predictive of overweight in childhood. The area under the receiver operator curve for multivariate prediction models including these metabolites and traditional risk factors was 0.77 for rapid growth and 0.82 for overweight, compared with 0.69 and 0.69, respectively, for models using traditional risk factors alone. Among the 43 pre-annotated metabolites, seven and five metabolites were nominally associated (P < 0.05) with rapid growth and overweight, respectively. The BCAA leucine, remained associated (1.6 × 10) with overweight after FDR correction.

Conclusion: The metabolites identified here may assist in the identification of children at risk of developing obesity and improve understanding of mechanisms involved in postnatal growth. Cholestenone and BCAAs are suggestive of a role of the gut microbiome and nutrient signalling respectively in child growth trajectories.
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http://dx.doi.org/10.1038/s41366-021-00888-1DOI Listing
July 2021

Longitudinal associations of physical activity with plasma metabolites among colorectal cancer survivors up to 2 years after treatment.

Sci Rep 2021 Jul 2;11(1):13738. Epub 2021 Jul 2.

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.

We investigated longitudinal associations of moderate-to-vigorous physical activity (MVPA) and light-intensity physical activity (LPA) with plasma concentrations of 138 metabolites after colorectal cancer (CRC) treatment. Self-reported physical activity data and blood samples were obtained at 6 weeks, and 6, 12 and 24 months post-treatment in stage I-III CRC survivors (n = 252). Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQp180 kit). Linear mixed models were used to evaluate confounder-adjusted longitudinal associations. Inter-individual (between-participant differences) and intra-individual associations (within-participant changes over time) were assessed as percentage difference in metabolite concentration per 5 h/week of MVPA or LPA. At 6 weeks post-treatment, participants reported a median of 6.5 h/week of MVPA (interquartile range:2.3,13.5) and 7.5 h/week of LPA (2.0,15.8). Inter-individual associations were observed with more MVPA being related (FDR-adjusted q-value < 0.05) to higher concentrations of arginine, citrulline and histidine, eight lysophosphatidylcholines, nine diacylphosphatidylcholines, 13 acyl-alkylphosphatidylcholines, two sphingomyelins, and acylcarnitine C10:1. No intra-individual associations were found. LPA was not associated with any metabolite. More MVPA was associated with higher concentrations of several lipids and three amino acids, which have been linked to anti-inflammatory processes and improved metabolic health. Mechanistic studies are needed to investigate whether these metabolites may affect prognosis.
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http://dx.doi.org/10.1038/s41598-021-92279-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253824PMC
July 2021

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.

Genome Biol 2021 06 29;22(1):194. Epub 2021 Jun 29.

Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.

Background: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.

Results: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.

Conclusion: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
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http://dx.doi.org/10.1186/s13059-021-02398-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243879PMC
June 2021

Association of markers of inflammation, the kynurenine pathway and B vitamins with age and mortality, and a signature of inflammaging.

J Gerontol A Biol Sci Med Sci 2021 Jun 12. Epub 2021 Jun 12.

Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.

Background: Inflammation is a key feature of aging. We aimed to i) investigate the association of 34 blood markers potentially involved in inflammatory processes with age and mortality, ii) develop a signature of 'inflammaging'.

Methods: Thirty-four blood markers relating to inflammation, B vitamin status and the kynurenine pathway were measured in 976 participants in the Melbourne Collaborative Cohort Study at baseline (median age=59 years) and follow-up (median age=70 years). Associations with age and mortality were assessed using linear and Cox regression, respectively. A parsimonious signature of inflammaging was developed and its association with mortality was compared with two marker scores calculated across all markers associated with age and mortality, respectively.

Results: The majority of markers (30/34) were associated with age, with stronger associations observed for neopterin, cystatin C, IL-6, TNF-α, several markers of the kynurenine pathway and derived indices KTR (kynurenine/tryptophan ratio), PAr index (ratio of 4-pyridoxic acid and the sum of pyridoxal 5´-phosphate and pyridoxal), and HK:XA (3-hydroxykynurenine/xanthurenic acid ratio). Many markers (17/34) showed an association with mortality, in particular IL-6, neopterin, CRP, quinolinic acid, PAr index, and KTR. The inflammaging signature included ten markers and was strongly associated of mortality (HR per SD=1.40, 95%CI:1.24-1.57, P=2x10 -8), similar to scores based on all age-associated (HR=1.38, 95%CI:1.23-1.55, P=4x10 -8) and mortality-associated markers (HR=1.43, 95%CI:1.28-1.60, P=1x10 -10), respectively. Strong evidence of replication of the inflammaging signature association with mortality was found in the Hordaland Health Study.

Conclusion: Our study highlights the key role of the kynurenine pathway and vitamin B6 catabolism in aging, along with other well-established inflammation-related markers. A signature of inflammaging based on ten markers was strongly associated with mortality.
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http://dx.doi.org/10.1093/gerona/glab163DOI Listing
June 2021

Are antigenic tests useful for detecting SARS-CoV-2 infections in patients accessing to emergency departments? Results from a North-West Italy hospital.

J Infect 2021 08 21;83(2):237-279. Epub 2021 May 21.

Department of Clinical and Biological Science, University of Turin, Regione Gonzole 10, Orbassano 10043, Italy; Epidemiology Unit, Regional Health Service ASL TO3, Grugliasco. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139186PMC
August 2021

Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption.

Nat Commun 2021 05 14;12(1):2830. Epub 2021 May 14.

Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.

Coffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. Here we report the results from epigenome-wide association studies (EWAS) on coffee and tea consumption in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis of coffee consumption reveals 11 CpGs surpassing the epigenome-wide significance threshold (P-value <1.1×10), which annotated to the AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH genes. Among them, cg14476101 is significantly associated with expression of the PHGDH and risk of fatty liver disease. Knockdown of PHGDH expression in liver cells shows a correlation with expression levels of genes associated with circulating lipids, suggesting a role of PHGDH in hepatic-lipid metabolism. EWAS meta-analysis on tea consumption reveals no significant association, only two CpGs annotated to CACNA1A and PRDM16 genes show suggestive association (P-value <5.0×10). These findings indicate that coffee-associated changes in DNA methylation levels may explain the mechanism of action of coffee consumption in conferring risk of diseases.
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http://dx.doi.org/10.1038/s41467-021-22752-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121846PMC
May 2021

Strategy for primary prevention of non-communicable diseases (NCD) and mitigation of climate change in Italy.

J Epidemiol Community Health 2021 Sep 29;75(9):917-924. Epub 2021 Apr 29.

International Agency for Research on Cancer, Lyon, Rhône-Alpes, France.

This paper derives from a document commissioned in 2019 by the Italian Minister of Health, and outlines a general strategy for primary prevention of non-communicable diseases in Italy, with a special focus on cobenefits of climate change mitigation. Given that action against climate change is primarily taken via energy choices, limiting the use of fossil fuels and promoting renewable sources, an effective strategy is one in which interventions are designed to prevent diseases and jointly mitigate climate change, the so-called cobenefits. For policies capable of producing relevant co-benefits we focus on three categories of interventions, urban planning, diet and transport that are of special importance. For example, policies promoting active transport (cycling, walking) have the triple effect of mitigating greenhouse gas emissions, preventing diseases related to atmospheric pollution, and increasing physical activity, thus preventing obesity and diabetes.In particular, we propose that for 2025 the following goals are achieved: reduce the prevalence of smokers by 30%, with particular emphasis on young people; reduce the prevalence of childhood obesity by 20%; reduce the proportion of calories obtained from ultraprocessed foods by 20%; reduce the consumption of alcohol by 10%; reduce the consumption of salt by 30%; reduce the consumption of sugary drinks by 20%; reduce the average consumption of meat by 20%; increase the weekly hours of exercise by 10%. The aim is to complement individual health promotion with structural policies (such as urban planning, taxation and incentives) which render the former more effective and result in a reduction in inequality. We strongly encourage the inclusion of primary prevention in all policies, in light of the described cobenefits. Italy's role as the cohost of the 2020 (now 2021) UN climate negotiations (COP26) presents the opportunity for international leadership in addressing health as an integral component of the response to climate change.
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http://dx.doi.org/10.1136/jech-2020-215726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372375PMC
September 2021

COVID-19 Research: Challenges to Interpret Numbers and Propose Solutions.

Front Public Health 2021;9:651089. Epub 2021 Apr 12.

School of Public Health, Imperial College, London, United Kingdom.

The response of the scientific community to the COVID-19 pandemic has been unprecedented in size, speed and discovery output. Within months of virus emergence, the SARS-CoV-2 genomics, replication, evolution and dissemination dynamics as well as natural history, infection risk and prognostic factors and biology of the disease have been gradually deciphered. More than 250 articles on COVID-19 published in Frontiers in Public Health have contributed to these insights. We discuss here some of the key research themes and challenges that have been addressed. We provide our perspective on current research issues with surveillance data quality and limitations of epidemiological methods. We warn against the potential misuse or misleading interpretation of public data of variable quality and the use of inadequate study designs for the evaluation of effect of non-pharmaceutical interventions. We conclude by interrogating possible public health strategies for pandemic control as well as discuss the ethical responsibilities and democratic accountability of researchers in their role as experts and policy advisors.
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http://dx.doi.org/10.3389/fpubh.2021.651089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072001PMC
May 2021

A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC.

Clin Gastroenterol Hepatol 2021 Apr 24. Epub 2021 Apr 24.

Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Background & Aims: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk.

Methods: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci.

Results: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04-1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02-1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04-1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93-0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90-0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90-0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92-0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94-0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93-0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92-0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons.

Conclusions: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.
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http://dx.doi.org/10.1016/j.cgh.2021.04.028DOI Listing
April 2021

Prospective Identification of Elevated Circulating CDCP1 in Patients Years before Onset of Lung Cancer.

Cancer Res 2021 Jul 11;81(13):3738-3748. Epub 2021 Feb 11.

MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.

Increasing evidence points to a role for inflammation in lung carcinogenesis. A small number of circulating inflammatory proteins have been identified as showing elevated levels prior to lung cancer diagnosis, indicating the potential for prospective circulating protein concentration as a marker of early carcinogenesis. To identify novel markers of lung cancer risk, we measured a panel of 92 circulating inflammatory proteins in 648 prediagnostic blood samples from two prospective cohorts in Italy and Norway (women only). To preserve the comparability of results and protect against confounding factors, the main statistical analyses were conducted in women from both studies, with replication sought in men (Italian participants). Univariate and penalized regression models revealed for the first time higher blood levels of CDCP1 protein in cases that went on to develop lung cancer compared with controls, irrespective of time to diagnosis, smoking habits, and gender. This association was validated in an additional 450 samples. Associations were stronger for future cases of adenocarcinoma where CDCP1 showed better explanatory performance. Integrative analyses combining gene expression and protein levels of CDCP1 measured in the same individuals suggested a link between CDCP1 and the expression of transcripts of LRRN3 and SEM1. Enrichment analyses indicated a potential role for CDCP1 in pathways related to cell adhesion and mobility, such as the WNT/β-catenin pathway. Overall, this study identifies lung cancer-related dysregulation of CDCP1 expression years before diagnosis. SIGNIFICANCE: Prospective proteomics analyses reveal an association between increased levels of circulating CDCP1 and lung carcinogenesis irrespective of smoking and years before diagnosis, and integrating gene expression indicates potential underlying mechanisms..
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611235PMC
July 2021

Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies.

Sci Rep 2021 Feb 4;11(1):3100. Epub 2021 Feb 4.

Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.

Individuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.
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http://dx.doi.org/10.1038/s41598-021-82714-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862626PMC
February 2021

Education, biological ageing, all-cause and cause-specific mortality and morbidity: UK biobank cohort study.

EClinicalMedicine 2020 Dec 19;29-30:100658. Epub 2020 Nov 19.

Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, Netherlands.

Background: Socioeconomic position as measured by education may be embodied and affect the functioning of key physiological systems. Links between social disadvantage, its biological imprint, and cause-specific mortality and morbidity have not been investigated in large populations, and yet may point towards areas for public health interventions beyond targeting individual behaviours.

Methods: Using data from 366,748 UK Biobank participants with 13 biomarker measurements, we calculated a Biological Health Score (BHS, ranging from 0 to 1) capturing the level of functioning of five physiological systems. Associations between BHS and incidence of cardiovascular disease (CVD) and cancer, and mortality from all, CVD, cancer, and external causes were examined. We explored the role of education in these associations. Mendelian randomisation using genetic evidence was used to triangulate these findings.

Findings: An increase in BHS of 0.1 was associated with all-cause (HR = 1.14 [1.12-1.16] and 1.09 [1.07-1.12] in men and women respectively), cancer (HR = 1.11 [1.09-1.14] and 1.07 [1.04-1.10]) and CVD (HR = 1.25 [1.20-1.31] and 1.21 [1.11-1.31]) mortality, CVD incidence (HR = 1.15 [1.13-1.16] and 1.17 [1.15-1.19]). These associations survived adjustment for education, lifestyle-behaviours, body mass index (BMI), co-morbidities and medical treatments. Mendelian randomisation further supported the link between the BHS and CVD incidence (HR = 1.31 [1.21-1.42]). The BHS contributed to CVD incidence prediction (age-adjusted C-statistic = 0.58), other than through education and health behaviours.

Interpretation: The BHS captures features of the embodiment of education, health behaviours, and more proximal unknown factors which all complementarily contribute to all-cause, cancer and CVD morbidity and premature death.
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http://dx.doi.org/10.1016/j.eclinm.2020.100658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788440PMC
December 2020

Comparison of smoking reduction with improvement of social conditions in early life: simulation in a British cohort.

Int J Epidemiol 2021 07;50(3):797-808

UMR1027, Toulouse III University, Inserm, Toulouse, France.

Background: Health care evaluation models can be useful to assign different levels of priority to interventions or policies targeting different age groups or different determinants of health. We aimed to assess early mortality in counterfactual scenarios implying reduced adverse childhood experience (ACE) and/or improved educational attainment (childhood and early life characteristics), compared with a counterfactual scenario implying reduced smoking in adulthood.

Methods: We used data from the 1958 National Child Development Study British birth cohort, which initially included 18 558 subjects. Applying a potential outcome approach, scenarios were simulated to estimate the expected mortality between ages 16 and 55 under a counterfactual decrease by half of the observed level of exposure to (i) ACE, (ii) low educational attainment (at age 22), (iii) ACE and low educational attainment (a combined exposure) and (iv) smoking at age 33. Estimations were obtained using g-computation, separately for men and women. Analyses were further stratified according to the parental level of education, to assess social inequalities.

Results: The study population included 12 164 members. The estimated decrease in mortality in the counterfactual scenarios with reduced ACE and improved educational attainment was close to the decreased mortality in the counterfactual scenario with reduced smoking, showing a relative difference in mortality of respectively -7.2% [95% CI (confidence interval) = (-12.2% to 1.2%)] versus -7.0% (-13.1% to +1.2%) for women, and -9.9% (-15.6% to -6.2%) versus -12.3% (-17.0% to -5.9%) for men.

Conclusions: Our results highlight the potential value of targeting early social characteristics such as ACE and education, compared with well-recognized interventions on smoking.
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http://dx.doi.org/10.1093/ije/dyaa244DOI Listing
July 2021

Commentary: Climate change and health: the importance of experiments.

Int J Epidemiol 2021 07;50(3):929-930

Department of Civil and Environmental Engineering, Imperial College London, London, UK.

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http://dx.doi.org/10.1093/ije/dyaa261DOI Listing
July 2021

Short-term personal and outdoor exposure to ultrafine and fine particulate air pollution in association with blood pressure and lung function in healthy adults.

Environ Res 2021 03 4;194:110579. Epub 2020 Dec 4.

Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, the Netherlands; Julius Center, University Medical Center Utrecht, Utrecht, the Netherlands.

Studies reporting on associations between short-term exposure to outdoor fine (PM), and ultrafine particles (UFP) and blood pressure and lung function have been inconsistent. Few studies have characterized exposure by personal monitoring, which especially for UFP may have resulted in substantial exposure measurement error. We investigated the association between 24-h average personal UFP, PM, and soot exposure and dose and the health parameters blood pressure and lung function. We further assessed the short-term associations between outdoor concentrations measured at a central monitoring site and near the residences and these health outcomes. We performed three 24-h personal exposure measurements for UFP, PM, and soot in 132 healthy adults from Basel (Switzerland), Amsterdam and Utrecht (the Netherlands), and Turin (Italy). Monitoring of each subject was conducted in different seasons in a one-year study period. Subject's activity levels and associated ventilation rates were measured using actigraphy to calculate the inhaled dose. After each 24-h monitoring session, blood pressure and lung function were measured. Contemporaneously with personal measurements, UFP, PM and soot were measured outdoor at the subject's residential address and at a central site in the research area. Associations between short-term personal and outdoor exposure and dose to UFP, PM, and soot and health outcomes were tested using linear mixed effect models. The 24-h mean personal, residential and central site outdoor UFP exposures were not associated with blood pressure or lung function. UFP mean exposures in the 2-h prior to the health test was also not associated with blood pressure and lung function. Personal, central site and residential PM exposure were positively associated with systolic blood pressure (about 1.4 mmHg increase per Interquartile range). Personal soot exposure and dose were positively associated with diastolic blood pressure (1.2 and 0.9 mmHg increase per Interquartile range). No consistent associations between PM or soot exposure and lung function were observed. Short-term personal, residential outdoor or central site exposure to UFP was not associated with blood pressure or lung function. Short-term personal PM and soot exposures were associated with blood pressure, but not lung function.
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http://dx.doi.org/10.1016/j.envres.2020.110579DOI Listing
March 2021

Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort.

Clin Gastroenterol Hepatol 2020 Dec 29. Epub 2020 Dec 29.

CIBER Epidemiología y Salud Pública, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.

Background & Aims: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

Methods: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression.

Results: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29-0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50-0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86-1.00) overall. Signature associations were stronger in male compared with female participants.

Conclusions: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.
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http://dx.doi.org/10.1016/j.cgh.2020.11.045DOI Listing
December 2020

The use of silicone wristbands to evaluate personal exposure to semi-volatile organic chemicals (SVOCs) in France and Italy.

Environ Pollut 2020 Dec 10;267:115490. Epub 2020 Sep 10.

O'Neill School of Public and Environmental Affairs, Indiana University, Bloomington, IN, United States. Electronic address:

In this exploratory study, we measured for the first-time human exposure to about 90 semi-volatile organic chemicals (SVOCs) in France and Italy using silicone wristbands. Participants in France (n = 40) and in Italy (n = 31) wore a silicone wristband for five days during 2018 and 2019. Samples were analyzed for 39 polybrominated diphenyl ethers (PBDEs), 10 novel brominated flame retardants (nBFRs), 25 organophosphate esters (OPEs), and 18 polycyclic aromatic hydrocarbons (PAHs). In both groups, the most commonly detected chemicals were BDE-209, BEHTBP, tris[(2R)-1-chloro-2-propyl] phosphate (TCIPP), and phenanthrene among PBDEs, nBFRs, OPEs, and PAHs, respectively. The concentrations of ∑ PBDEs, ∑ nBFRs, ∑ OPEs, ∑ PAHs, and of most individual chemicals were generally significantly higher in samples from France than in those from Italy, except for BDE-209 and TCIPP. On a broader scale, the chemical concentrations were generally significantly lower in this study than those measured in the United States in previous studies using the same type of wristbands. Efforts to standardize the protocols for the use of silicone wristbands are still needed but this study shows that wristbands are capable of capturing regional differences in human exposure to a large variety of SVOCs and, therefore, can be used as personal exposure monitor for studies with global coverage.
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http://dx.doi.org/10.1016/j.envpol.2020.115490DOI Listing
December 2020

The COVID-19 pandemic and global environmental change: Emerging research needs.

Environ Int 2021 01 19;146:106272. Epub 2020 Nov 19.

RECETOX, Masaryk University, Czech Republic.

The outbreak of COVID-19 raised numerous questions on the interactions between the occurrence of new infections, the environment, climate and health. The European Union requested the H2020 HERA project which aims at setting priorities in research on environment, climate and health, to identify relevant research needs regarding Covid-19. The emergence and spread of SARS-CoV-2 appears to be related to urbanization, habitat destruction, live animal trade, intensive livestock farming and global travel. The contribution of climate and air pollution requires additional studies. Importantly, the severity of COVID-19 depends on the interactions between the viral infection, ageing and chronic diseases such as metabolic, respiratory and cardiovascular diseases and obesity which are themselves influenced by environmental stressors. The mechanisms of these interactions deserve additional scrutiny. Both the pandemic and the social response to the disease have elicited an array of behavioural and societal changes that may remain long after the pandemic and that may have long term health effects including on mental health. Recovery plans are currently being discussed or implemented and the environmental and health impacts of those plans are not clearly foreseen. Clearly, COVID-19 will have a long-lasting impact on the environmental health field and will open new research perspectives and policy needs.
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http://dx.doi.org/10.1016/j.envint.2020.106272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674147PMC
January 2021

The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk.

BMC Cancer 2020 Nov 23;20(1):1138. Epub 2020 Nov 23.

UMR LEASP, Université de Toulouse III, UPS, Inserm, Toulouse, France.

Background: Women with an advantaged socioeconomic position (SEP) have a higher risk of developing breast cancer (BC). The reasons for this association do not seem to be limited to reproductive factors and remain to be understood. We aimed to investigate the impact of lifecourse SEP from childhood and social mobility on the risk of BC considering a broad set of potential mediators.

Methods: We used a discovery-replication strategy in two European prospective cohorts, E3N (N = 83,436) and EPIC-Italy (N = 20,530). In E3N, 7877 women were diagnosed with BC during a median 24.4 years of follow-up, while in EPIC-Italy, 893 BC cases were diagnosed within 15.1 years. Hazard ratios (HR) were estimated using Cox proportional hazard models on imputed data.

Results: In E3N, women with higher education had a higher risk of BC (HR [95%CI] = 1.21 [1.12, 1.30]). This association was attenuated by adjusting for reproductive factors, in particular age at first childbirth (HR[95%CI] = 1.13 [1.04, 1.22]). Health behaviours, anthropometric variables, and BC screening had a weaker effect on the association. Women who remained in a stable advantaged SEP had a higher risk of BC (HR [95%CI] = 1.24 [1.07; 1.43]) attenuated after adjustment for potential mediators (HR [95%CI] = 1.13 [0.98; 1.31]). These results were replicated in EPIC-Italy.

Conclusions: These results confirm the important role of reproductive factors in the social gradient in BC risk, which does not appear to be fully explained by the large set of potential mediators, including cancer screening, suggesting that further research is needed to identify additional mechanisms.
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http://dx.doi.org/10.1186/s12885-020-07648-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684912PMC
November 2020

Metabolic profiles of socio-economic position: a multi-cohort analysis.

Int J Epidemiol 2021 07;50(3):768-782

Department of Epidemiology and Biostatistics, MRC Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.

Background: Low socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear.

Methods: We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in ∼30 000 adults and 4000 children across 10 UK and Finnish cohort studies.

Results: In risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared with non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids.

Conclusions: Our work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavourable metabolic profile, consistent across ages and cohorts. The metabolites we found to be associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities.
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http://dx.doi.org/10.1093/ije/dyaa188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271201PMC
July 2021

Life-course socioeconomic disadvantage and lung function: a multicohort study of 70 496 individuals.

Eur Respir J 2021 03 18;57(3). Epub 2021 Mar 18.

Center for Primary Care and Public Health (UNISANTE), University of Lausanne, Lausanne, Switzerland.

Background: Lung function is an important predictor of health and a marker of physical functioning at older ages. This study aimed to quantify the years of lung function lost according to disadvantaged socioeconomic conditions across the life-course.

Methods: This multicohort study used harmonised individual-level data from six European cohorts with information on life-course socioeconomic disadvantage and lung function assessed by forced expiratory volume in 1 s (FEV) and forced vital capacity (FVC). 70 496 participants (51% female) aged 18-93 years were included. Socioeconomic disadvantage was measured in early life (low paternal occupational position), early adulthood (low educational level) and adulthood (low occupational position). Risk factors for poor lung function ( smoking, obesity, sedentary behaviour, cardiovascular and respiratory diseases) were included as potential mediators. The years of lung function lost due to socioeconomic disadvantage were computed at each life stage.

Results: Socioeconomic disadvantage during the life-course was associated with a lower FEV. By the age of 45 years, individuals experiencing disadvantaged socioeconomic conditions had lost 4-5 years of healthy lung function their more advantaged counterparts (low educational level -4.36 (95% CI -7.33--2.37) for males and -5.14 (-10.32--2.71) for females; low occupational position -5.62 (-7.98--4.90) for males and -4.32 (-13.31--2.27) for females), after accounting for the risk factors for lung function. By the ages of 65 years and 85 years, the years of lung function lost due to socioeconomic disadvantage decreased by 2-4 years, depending on the socioeconomic indicator. Sensitivity analysis using FVC yielded similar results to those using FEV.

Conclusion: Life-course socioeconomic disadvantage is associated with lower lung function and predicts a significant number of years of lung function loss in adulthood and at older ages.
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http://dx.doi.org/10.1183/13993003.01600-2020DOI Listing
March 2021

GrimAge Outperforms Other Epigenetic Clocks in the Prediction of Age-Related Clinical Phenotypes and All-Cause Mortality.

J Gerontol A Biol Sci Med Sci 2021 04;76(5):741-749

Department of Medical Gerontology, Trinity College Dublin, Ireland.

The aging process is characterized by the presence of high interindividual variation between individuals of the same chronical age prompting a search for biomarkers that capture this heterogeneity. Epigenetic clocks measure changes in DNA methylation levels at specific CpG sites that are highly correlated with calendar age. The discrepancy resulting from the regression of DNA methylation age on calendar age is hypothesized to represent a measure of biological aging with a positive/negative residual signifying age acceleration (AA)/deceleration, respectively. The present study examines the associations of 4 epigenetic clocks-Horvath, Hannum, PhenoAge, GrimAge-with a wide range of clinical phenotypes (walking speed, grip strength, Fried frailty, polypharmacy, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), Sustained Attention Reaction Time, 2-choice reaction time), and with all-cause mortality at up to 10-year follow-up, in a sample of 490 participants in the Irish Longitudinal Study on Ageing (TILDA). HorvathAA and HannumAA were not predictive of health; PhenoAgeAA was associated with 4/9 outcomes (walking speed, frailty MOCA, MMSE) in minimally adjusted models, but not when adjusted for other social and lifestyle factors. GrimAgeAA by contrast was associated with 8/9 outcomes (all except grip strength) in minimally adjusted models, and remained a significant predictor of walking speed, .polypharmacy, frailty, and mortality in fully adjusted models. Results indicate that the GrimAge clock represents a step-improvement in the predictive utility of the epigenetic clocks for identifying age-related decline in an array of clinical phenotypes promising to advance precision medicine.
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http://dx.doi.org/10.1093/gerona/glaa286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087266PMC
April 2021
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