1078 results found
Francavilla A, Ferrero G, Pardini B, et al., 2023, Gluten-free diet affects fecal small non-coding RNA profiles and microbiome composition in celiac disease supporting a host-gut microbiota crosstalk, GUT MICROBES, Vol: 15, ISSN: 1949-0976
Wu WY-Y, Haider Z, Feng X, et al., 2023, Assessment of the EarlyCDT-Lung test as an early biomarker of lung cancer in ever-smokers - A retrospective nested case-control study in two prospective cohorts, International Journal of Cancer, Vol: 152, Pages: 2002-2010, ISSN: 0020-7136
The EarlyCDT-Lung test is a blood-based autoantibody assay intended to identify high-risk individuals for low-dose computed tomography lung cancer screening. However, there is a paucity of evidence on the performance of the EarlyCDT-Lung test in ever-smokers. We conducted a nested case-control study within two prospective cohorts to evaluate the risk-discriminatory performance of the EarlyCDT-Lung test using pre-diagnostic blood samples from 154 future lung cancer cases and 154 matched controls. Cases were selected from those who had ever smoked and had a pre-diagnostic blood samples less than 3 years prior to diagnosis. Conditional logistic regression was used to estimate the association between EarlyCDT-Lung test results and lung cancer risk. Sensitivity and specificity of the EarlyCDT-Lung test were calculated in all subjects and subgroups based on age, smoking history, lung cancer stage, sample collection time before diagnosis and year of sample collection. The overall lung cancer odds ratios were 0.89 (95% CI, 0.34-2.30) for a moderate risk EarlyCDT-Lung test result and 1.09 (95% CI, 0.48-2.47) for a high-risk test result compared to no significant test result. The overall sensitivity was 8.4% (95% CI, 4.6-14) and overall specificity was 92% (95% CI, 87-96) when considering a high-risk result as positive. Stratified analysis indicated higher sensitivity (17%, 95% CI, 7.2-32.1) in subjects with blood drawn up to 1 year prior to diagnosis. In conclusion, our study does not support a role of the EarlyCDT-Lung test in identifying the high-risk subjects in ever-smokers for lung cancer screening in the EPIC and NSHDS cohorts.
Ciccarelli D, Christopher Braddock D, Surman AJ, et al., 2023, Enhanced selectivity for acidic contaminants in drinking water: From suspect screening to toxicity prediction, Journal of Hazardous Materials, Vol: 448, Pages: 1-12, ISSN: 0304-3894
A novel analytical workflow for suspect screening of organic acidic contaminants in drinking water is presented, featuring selective extraction by silica-based strong anion-exchange solid-phase extraction, mixed-mode liquid chromatography-high resolution accurate mass spectrometry (LC-HRMS), peak detection, feature reduction and compound identification. The novel use of an ammonium bicarbonate-based elution solvent extended strong anion-exchange solid-phase extraction applicability to LC-HRMS of strong acids. This approach performed with consistently higher recovery and repeatability (88 ± 7 % at 500 ng L-1), improved selectivity and lower matrix interference (mean = 12 %) over a generic mixed-mode weak anion exchange SPE method. In addition, a novel filter for reducing full-scan features from fulvic and humic acids was successfully introduced, reducing workload and potential for false positives. The workflow was then applied to 10 London municipal drinking water samples, revealing the presence of 22 confirmed and 37 tentatively identified substances. Several poorly investigated and potentially harmful compounds were found which included halogenated hydroxy-cyclopentene-diones and dibromomethanesulfonic acid. Some of these compounds have been reported as mutagenic in test systems and thus their presence here requires further investigation. Overall, this approach demonstrated that employing selective extraction improved detection and helped shortlist suspects and potentially toxic chemical contaminants with higher confidence.
Schroers-Martin JG, Soo J, Brisou G, et al., 2023, Tracing founder mutations in circulating and tissue-resident follicular lymphoma precursors., Cancer Discov
Follicular lymphomas (FL) are characterized by BCL2 translocations, often detectable in blood years before FL diagnosis, but also observed in aging healthy individuals suggesting additional lesions are required for lymphomagenesis. We directly characterized early cooperating mutations by ultra-deep sequencing of pre-diagnostic blood and tissue specimens from 48 subjects who ultimately developed FL. Strikingly, CREBBP lysine acetyltransferase (KAT) domain mutations were the most commonly observed precursor lesions, and largely distinguished patients developing FL (14/48, 29%) from healthy adults with or without detected BCL2 rearrangements (0/13, p=0.03 and 0/20, p=0.007, respectively). CREBBP variants were detectable a median of 5.8 years before FL diagnosis, were clonally selected in FL tumors, and appeared restricted to the committed B-cell lineage. These results suggest that mutations affecting the CREBBP KAT domain are common lesions in FL cancer precursor cells (CPC), with potential for discriminating subjects at risk of developing FL or monitoring residual disease.
Kliemann N, Rauber F, Levy R, et al., 2023, Food processing and cancer risk in Europe: results from the prospective EPIC cohort study, The Lancet Planetary Health, Vol: 7, Pages: E219-E232, ISSN: 2542-5196
BackgroundFood processing has been hypothesised to play a role in cancer development; however, data from large-scale epidemiological studies are scarce. This study investigated the association between dietary intake according to amount of food processing and risk of cancer at 25 anatomical sites using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.MethodsThis study used data from the prospective EPIC cohort study, which recruited participants between March 18, 1991, and July 2, 2001, from 23 centres in ten European countries. Participant eligibility within each cohort was based on geographical or administrative boundaries. Participants were excluded if they had a cancer diagnosis before recruitment, had missing information for the NOVA food processing classification, or were within the top and bottom 1% for ratio of energy intake to energy requirement. Validated dietary questionnaires were used to obtain information on food and drink consumption. Participants with cancer were identified using cancer registries or during follow-up from a combination of sources, including cancer and pathology centres, health insurance records, and active follow-up of participants. We performed a substitution analysis to assess the effect of replacing 10% of processed foods and ultra-processed foods with 10% of minimally processed foods on cancer risk at 25 anatomical sites using Cox proportional hazard models.Findings521 324 participants were recruited into EPIC, and 450 111 were included in this analysis (318 686 [70·8%] participants were female individuals and 131 425 [29·2%] were male individuals). In a multivariate model adjusted for sex, smoking, education, physical activity, height, and diabetes, a substitution of 10% of processed foods with an equal amount of minimally processed foods was associated with reduced risk of overall cancer (hazard ratio 0·96, 95% CI 0·95–0·9
Rothwell JA, Bešević J, Dimou N, et al., 2023, Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts, BMC Medicine, Vol: 21, Pages: 1-13, ISSN: 1741-7015
BACKGROUND: Amino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts. METHODS: Concentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases. RESULTS: Histidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69-0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87-0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75-0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89-1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded. CONCLUSIONS: Higher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted.
Allione A, Viberti C, Cotellessa I, et al., 2023, Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma: the EPIC prospective cohort, International Journal of Cancer, Vol: 152, Pages: 725-737, ISSN: 0020-7136
Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive non-invasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM pre-diagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within five years from enrolment (n=36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex, PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than five years before diagnosis [AUC (area under the curve) < 5 years=0.89; AUC 5-10 years=0.80; AUC >10 years=0.75; baseline AUC range=0.63-0.67)]. DNAm changes as non-invasive biomarkers in pre-diagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk in order to possibly adopt more intensive monitoring for early disease identification.
Vaccarella S, Georges D, Bray F, et al., 2023, Socioeconomic inequalities in cancer mortality between and within countries in Europe: a population-based study., Lancet Reg Health Eur, Vol: 25
BACKGROUND: Reducing socioeconomic inequalities in cancer is a priority for the public health agenda. A systematic assessment and benchmarking of socioeconomic inequalities in cancer across many countries and over time in Europe is not yet available. METHODS: Census-linked, whole-of-population cancer-specific mortality data by socioeconomic position, as measured by education level, and sex were collected, harmonized, analysed, and compared across 18 countries during 1990-2015, in adults aged 40-79. We computed absolute and relative educational inequalities; temporal trends using estimated-annual-percentage-changes; the share of cancer mortality linked to educational inequalities. FINDINGS: Everywhere in Europe, lower-educated individuals have higher mortality rates for nearly all cancer-types relative to their more highly-educated counterparts, particularly for tobacco/infection-related cancers [relative risk of lung cancer mortality for lower- versus higher-educated = 2.4 (95% confidence intervals: 2.1-2.8) among men; = 1.8 (95% confidence intervals: 1.5-2.1) among women]. However, the magnitude of inequalities varies greatly by country and over time, predominantly due to differences in cancer mortality among lower-educated groups, as for many cancer-types higher-educated have more similar (and lower) rates, irrespective of the country. Inequalities were generally greater in Baltic/Central/East-Europe and smaller in South-Europe, although among women large and rising inequalities were found in North-Europe (relative risk of all cancer mortality for lower- versus higher-educated ≥1.4 in Denmark, Norway, Sweden, Finland and the England/Wales). Among men, rate differences (per 100,000 person-years) in total-cancer mortality for lower-vs-higher-educated groups ranged from 110 (Sweden) to 559 (Czech Republic); among women from approximately null (Slovenia, Italy, Spain) to 176 (Denmark). Lung cancer was the largest contributor to inequalities in t
de la Torre JA, Ronaldson A, Alonso J, et al., 2023, The relationship between air pollution and multimorbidity: Can two birds be killed with the same stone?, EUROPEAN JOURNAL OF EPIDEMIOLOGY, ISSN: 0393-2990
Alfano R, Zugna D, Barros H, et al., 2023, Cord blood epigenome-wide meta-analysis in six European-based child cohorts identifies signatures linked to rapid weight growth, BMC Medicine, Vol: 21, ISSN: 1741-7015
BACKGROUND: Rapid postnatal growth may result from exposure in utero or early life to adverse conditions and has been associated with diseases later in life and, in particular, with childhood obesity. DNA methylation, interfacing early-life exposures and subsequent diseases, is a possible mechanism underlying early-life programming. METHODS: Here, a meta-analysis of Illumina HumanMethylation 450K/EPIC-array associations of cord blood DNA methylation at single CpG sites and CpG genomic regions with rapid weight growth at 1 year of age (defined with reference to WHO growth charts) was conducted in six European-based child cohorts (ALSPAC, ENVIRONAGE, Generation XXI, INMA, Piccolipiù, and RHEA, N = 2003). The association of gestational age acceleration (calculated using the Bohlin epigenetic clock) with rapid weight growth was also explored via meta-analysis. Follow-up analyses of identified DNA methylation signals included prediction of rapid weight growth, mediation of the effect of conventional risk factors on rapid weight growth, integration with transcriptomics and metabolomics, association with overweight in childhood (between 4 and 8 years), and comparison with previous findings. RESULTS: Forty-seven CpGs were associated with rapid weight growth at suggestive p-value <1e-05 and, among them, three CpGs (cg14459032, cg25953130 annotated to ARID5B, and cg00049440 annotated to KLF9) passed the genome-wide significance level (p-value <1.25e-07). Sixteen differentially methylated regions (DMRs) were identified as associated with rapid weight growth at false discovery rate (FDR)-adjusted/Siddak p-values < 0.01. Gestational age acceleration was associated with decreasing risk of rapid weight growth (p-value = 9.75e-04). Identified DNA methylation signals slightly increased the prediction of rapid weight growth in addition to conventional risk factors. Among the identified signals, three CpGs partially mediated the effect of gestational age on rapid weigh
Macciotta A, Catalano A, Giraudo MT, et al., 2023, Mediating role of lifestyle behaviours in the association between education and cancer: results from the European Prospective Investigation into Cancer and Nutrition., Cancer Epidemiology, Biomarkers and Prevention, Vol: 32, Pages: 132-140, ISSN: 1055-9965
BACKGROUND: Many studies have shown that socioeconomic position (SEP) is associated with the incidence of malignant tumors at different sites. This study aims to estimate the association between educational level (as proxy for SEP) and cancer incidence and to understand if the observed associations might be partially explained by lifestyle behaviors. METHODS: The analyses were performed on data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, globally and by sex. We used Cox proportional hazards models together with mediation analysis to disentangle the total effect (TE) of educational level (measured through the Relative Index of Inequality (RII)) on cancer incidence into pure direct (PDE) and total indirect (TIE) effect, unexplained and explained by mediators, respectively. PDE and TIE were then combined to compute the proportions mediated (PM). RESULTS: After an average of 14 years of follow-up, 52,422 malignant tumors were ascertained. Low educated participants showed higher risk of developing stomach, lung, kidney (in women), and bladder (in men) cancers, and, conversely, lower risk of melanoma and breast cancer (in post-menopausal women), when compared to more educated participants. Mediation analyses showed that portions of the total effect of RII on cancer could be explained by site-specific related lifestyle behaviors for stomach, lung, and breast (in women). CONCLUSIONS: Cancer incidence in Europe is determined at least in part by a socioeconomically stratified distribution of risk factors. IMPACT: These observational findings support policies to reduce cancer occurrence by altering mediators, such as lifestyle behaviors, particularly focusing on underprivileged strata of the population.
Villanueva CM, Evlampidou I, Ibrahim F, et al., 2023, Global assessment of chemical quality of drinking water: The case of trihalomethanes, WATER RESEARCH, Vol: 230, ISSN: 0043-1354
Petrovic D, Carmeli C, Sandoval JL, et al., 2023, Life-course socioeconomic factors are associated with markers of epigenetic aging in a population-based study, Psychoneuroendocrinology, Vol: 147, Pages: 1-10, ISSN: 0306-4530
Adverse socioeconomic circumstances negatively affect the functioning of biological systems, but the underlying mechanisms remain only partially understood. Here, we explore the associations between life-course socioeconomic factors and four markers of epigenetic aging in a population-based setting.We included 684 participants (52 % women, mean age 52.6 ± 15.5 years) from a population and family-based Swiss study. We used nine life-course socioeconomic indicators as the main exposure variables, and four blood-derived, second generation markers of epigenetic aging as the outcome variables (Levine’s DNAmPhenoAge, DunedinPoAm38, GrimAge epigenetic age acceleration (EAA), and the mortality risk score (MS)). First, we investigated the associations between socioeconomic indicators and markers of epigenetic aging via mixed-effect linear regression models, adjusting for age, sex, participant’s recruitment center, familial structure (random-effect covariate), seasonality of blood sampling, and technical covariates. Second, we implemented counterfactual mediation analysis to investigate life-course and intermediate mechanisms underlying the socioeconomic gradient in epigenetic aging. Effect-size estimates were assessed using regression coefficients and counterfactual mediation parameters, along with their respective 95 % confidence intervals.Individuals reporting a low father’s occupation, adverse financial conditions in childhood, a low income, having financial difficulties, or experiencing unfavorable socioeconomic trajectories were epigenetically older and had a higher mortality risk score than their more advantaged counterparts. Specifically, this corresponded to an average increase of 1.1–1.5 years for Levine’s epigenetic age (β and 95 %CI range, β (minimum and maximum): 1.1–1.5 95 %CI[0.0–0.2; 2.3–3.0]), 1.1–1.5 additional years for GrimAge (β: 1.1–1.5 95 %CI[0.2–0.6; 1.9–3.0])
Sara DM, Minelli C, Broccia G, et al., 2023, COVID-19 and non-Hodgkin's lymphoma: A common susceptibility pattern?, PLoS One, Vol: 18
OBJECTIVE: To explore the link between COVID-19 incidence, socio-economic covariates, and NHL incidence. DESIGN: Ecological study design. SETTING: Sardinia, Italy. PARTICIPANTS: We used official reports on the total cases of COVID-19 in 2020, published data on NHL incidence, and socio-economic indicators by administrative unit, covering the whole regional population. MAIN OUTCOMES AND MEASURES: We used multivariable regression analysis to explore the association between the natural logarithm (ln) of the 2020 cumulative incidence of COVID-19 and the ln-transformed NHL incidence in 1974-2003, weighing by population size and adjusting by socioeconomic deprivation and other covariates. RESULTS: The cumulative incidence of COVID-19 increased in relation to past incidence of NHL (p < 0.001), socioeconomic deprivation (p = 0.006), and proportion of elderly residents (p < 0.001) and decreased with urban residency (p = 0.001). Several sensitivity analyses confirmed the finding of an association between COVID-19 and NHL. CONCLUSION: This ecological study found an ecological association between NHL and COVID-19. If further investigation would confirm our findings, shared susceptibility factors should be investigated among the plausible underlying mechanisms.
Casalone E, Birolo G, Pardini B, et al., 2022, Serum extracellular vesicle-derived microRNAs as potential biomarkers for pleural mesothelioma in a European prospective study, Cancers, Vol: 15, Pages: 1-15, ISSN: 2072-6694
Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort, we screened the whole miRNome in serum extracellular vesicles (EVs) of preclinical MPM cases. In a subgroup of 20 preclinical samples collected five years prior MPM diagnosis, we observed an upregulation of miR-11400 (fold change (FC) = 2.6, adjusted p-value = 0.01), miR-148a-3p (FC = 1.5, p-value = 0.001), and miR-409-3p (FC = 1.5, p-value = 0.04) relative to matched controls. The 3-miRNA panel showed a good classification capacity with an area under the receiver operating characteristic curve (AUC) of 0.81 (specificity = 0.75, sensitivity = 0.70). The diagnostic ability of the model was also evaluated in an independent retrospective cohort, yielding a higher predictive power (AUC = 0.86). A signature of EV miRNA can be detected up to five years before MPM; moreover, the identified miRNAs could provide functional insights into the molecular changes related to the late carcinogenic process, preceding MPM development.
Vineis P, 2022, What does scientific publishing in public health mean?, FRONTIERS IN PUBLIC HEALTH, Vol: 10
Gagliardi A, Francescato G, Ferrero G, et al., 2022, The 8q24 region hosts miRNAs altered in biospecimens of colorectal and bladder cancer patients, CANCER MEDICINE, ISSN: 2045-7634
Roca-Barcelo A, Fecht D, Pirani M, et al., 2022, Trends in temperature-associated mortality in Sao Paulo (Brazil) between 2000 and 2018: an example of disparities in adaptation to cold and heat, Journal of Urban Health: Bulletin of the New York Academy of Medicine, Vol: 99, Pages: 1012-1026, ISSN: 1099-3460
Exposure to non-optimal temperatures remains the single most deathful direct climate change impact to health. The risk varies based on the adaptation capacity of the exposed population which can be driven by climatic and/or non-climatic factors subject to fluctuations over time. We investigated temporal changes in the exposure–response relationship between daily mean temperature and mortality by cause of death, sex, age, and ethnicity in the megacity of São Paulo, Brazil (2000–2018). We fitted a quasi-Poisson regression model with time-varying distributed-lag non-linear model (tv-DLNM) to obtain annual estimates. We used two indicators of adaptation: trends in the annual minimum mortality temperature (MMT), i.e., temperature at which the mortality rate is the lowest, and in the cumulative relative risk (cRR) associated with extreme cold and heat. Finally, we evaluated their association with annual mean temperature and annual extreme cold and heat, respectively to assess the role of climatic and non-climatic drivers. In total, we investigated 4,471,000 deaths from non-external causes. We found significant temporal trends for both the MMT and cRR indicators. The former was decoupled from changes in AMT, whereas the latter showed some degree of alignment with extreme heat and cold, suggesting the role of both climatic and non-climatic adaptation drivers. Finally, changes in MMT and cRR varied substantially by sex, age, and ethnicity, exposing disparities in the adaptation capacity of these population groups. Our findings support the need for group-specific interventions and regular monitoring of the health risk to non-optimal temperatures to inform urban public health policies.
Vineis P, 2022, Invited Perspective: The Mysterious Case of Social Determinants of Health, ENVIRONMENTAL HEALTH PERSPECTIVES, Vol: 130, ISSN: 0091-6765
Handakas E, Chang K, Khandpur N, et al., 2022, Metabolic profiles of ultra-processed food consumption and their role in obesity risk in British children, Clinical Nutrition, Vol: 41, Pages: 2537-2548, ISSN: 0261-5614
Background & aimsHigher consumption of ultra-processed foods (UPF) has been associated with childhood obesity, but underlying mechanisms remain unclear. We investigated plasma nuclear magnetic resonance metabolic profiles of higher UPF consumption and their role in obesity risk in the British ALSPAC cohort.MethodsWe performed cross-sectional and prospective metabolome wide association analyses of UPF, calculated from food diaries using the NOVA classification. In cross-sectional analysis, we tested the association between UPF consumption and metabolic profile at 7 years (N = 4528), and in the prospective analysis we tested the association between UPF consumption at 13 years and metabolic profile at 17 years (N = 3086). Effects of UPF-associated metabolites at 7 years on subsequent fat mass accumulation were assessed using growth curve models.ResultsAt 7 years, UPF was associated with 115 metabolic traits including lower levels of branched-chain and aromatic amino acids and higher levels of citrate, glutamine, and monounsaturated fatty acids, which were also associated with greater fat mass accumulation. Reported intake of nutrients mediated associations with most metabolites, except for citrate.ConclusionsUPF consumption among British children is associated with perturbation of multiple metabolic traits, many of which contribute to child obesity risk.
Berndt S, Vijai J, Benavente Y, et al., 2022, Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes, LEUKEMIA, ISSN: 0887-6924
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Freni-Sterrantino A, Fiorito G, D'Errico A, et al., 2022, Association between work characteristics and epigenetic age acceleration: cross-sectional results from UK - Understanding Society study, AGING-US, Vol: 14, ISSN: 1945-4589
Freni Sterrantino A, Fiorito G, D'errico A, et al., 2022, Association between work characteristics and epigenetic age acceleration: cross-sectional results from UK – Understanding Society study, Aging, Vol: 14, Pages: 7752-7773, ISSN: 1945-4589
Occupation-related stress and work characteristics are possible determinants of social inequalities in epigenetic aging but have been little investigated. Here, we investigate the association of several work characteristics with epigenetic age acceleration (AA) biomarkers.The study population included employed and unemployed men and women (n=631) from UK Understanding Society study. We evaluated the association of employment and work characteristics related to job type, job stability; job schedule; autonomy and influence at work; occupational physical activity; and feelings regarding the job with four epigenetic age acceleration biomarkers (Hannum, Horvath, PhenoAge, GrimAge) and pace of aging (DunedinPoAm, DunedinPACE). We fitted linear regression models, unadjusted and adjusted for established risk factors, and found the following associations for unemployment (years of acceleration): HorvathAA (1.51, 95%CI 0.08,2.95), GrimAgeAA (1.53, 95%CI 0.16,2.90) and 3.21 years for PhenoAA (95%CI 0.89,5.33). Job insecurity increased PhenoAA (1.83, 95%CI 0.003,3.67), while working at night was associated with an increase of 2.12 years in GrimAgeAA (95%CI 0.69,3.55). We found effects of unemployment to be stronger in men and effects of night shift work to be stronger in women. These results provide evidence of associations between unemployment with accelerated ageing and suggest that insecure employment and night work may also increase age acceleration. Our findings have implications for policies relating to current changes in working conditions and highlight the utility of biological age biomarkers in studies in younger populations without long-term health information.
Smith-Byrne K, Cerani A, Guida F, et al., 2022, Circulating Isovalerylcarnitine and Lung Cancer Risk: Evidence from Mendelian Randomization and Prediagnostic Blood Measurements, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 31, Pages: 1966-1974, ISSN: 1055-9965
Mantovani A, Morrone MC, Patrono C, et al., 2022, Long Covid: where we stand and challenges ahead., Cell Death Differ, Vol: 29, Pages: 1891-1900
Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially as Long Covid, has been defined as a constellation of signs and symptoms which persist for weeks or months after the initial SARS-CoV-2 infection. PASC affects a wide range of diverse organs and systems, with manifestations involving lungs, brain, the cardiovascular system and other organs such as kidney and the neuromuscular system. The pathogenesis of PASC is complex and multifactorial. Evidence suggests that seeding and persistence of SARS-CoV-2 in different organs, reactivation, and response to unrelated viruses such as EBV, autoimmunity, and uncontrolled inflammation are major drivers of PASC. The relative importance of pathogenetic pathways may differ in different tissue and organ contexts. Evidence suggests that vaccination, in addition to protecting against disease, reduces PASC after breakthrough infection although its actual impact remains to be defined. PASC represents a formidable challenge for health care systems and dissecting pathogenetic mechanisms may pave the way to targeted preventive and therapeutic approaches.
Cappozzo A, McCrory C, Robinson O, et al., 2022, A blood DNA methylation biomarker for predicting short-term risk of cardiovascular events, Clinical Epigenetics, Vol: 14, ISSN: 1868-7083
Background:Recent evidence highlights the epidemiological value of blood DNA methylation (DNAm) as surrogate biomarker for exposure to risk factors for non-communicable diseases (NCD). DNAm surrogate of exposures predicts diseases and longevity better than self-reported or measured exposures in many cases. Consequently, disease prediction models based on blood DNAm surrogates may outperform current state-of-the-art prediction models. This study aims to develop novel DNAm surrogates for cardiovascular diseases (CVD) risk factors and develop a composite biomarker predictive of CVD risk. We compared the prediction performance of our newly developed risk score with the state-of-the-art DNAm risk scores for cardiovascular diseases, the ‘next-generation’ epigenetic clock DNAmGrimAge, and the prediction model based on traditional risk factors SCORE2.Results:Using data from the EPIC Italy cohort, we derived novel DNAm surrogates for BMI, blood pressure, fasting glucose and insulin, cholesterol, triglycerides, and coagulation biomarkers. We validated them in four independent data sets from Europe and the USA. Further, we derived a DNAmCVDscore predictive of the time-to-CVD event as a combination of several DNAm surrogates. ROC curve analyses show that DNAmCVDscore outperforms previously developed DNAm scores for CVD risk and SCORE2 for short-term CVD risk. Interestingly, the performance of DNAmGrimAge and DNAmCVDscore was comparable (slightly lower for DNAmGrimAge, although the differences were not statistically significant).Conclusions:We described novel DNAm surrogates for CVD risk factors useful for future molecular epidemiology research, and we described a blood DNAm-based composite biomarker, DNAmCVDscore, predictive of short-term cardiovascular events. Our results highlight the usefulness of DNAm surrogate biomarkers of risk factors in epigenetic epidemiology to identify high-risk populations. In addition, we provide further evidence on the effectiveness of
Dugue P-A, Bodelon C, Chung FF, et al., 2022, Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies, Breast Cancer Research, Vol: 24, Pages: 1-9, ISSN: 1465-542X
BackgroundDNA methylation in blood may reflect adverse exposures accumulated over the lifetime and could therefore provide potential improvements in the prediction of cancer risk. A substantial body of research has shown associations between epigenetic aging and risk of disease, including cancer. Here we aimed to study epigenetic measures of aging and lifestyle-related factors in association with risk of breast cancer.MethodsUsing data from four prospective case–control studies nested in three cohorts of European ancestry participants, including a total of 1,655 breast cancer cases, we calculated three methylation-based measures of lifestyle factors (body mass index [BMI], tobacco smoking and alcohol consumption) and seven measures of epigenetic aging (Horvath-based, Hannum-based, PhenoAge and GrimAge). All measures were regression-adjusted for their respective risk factors and expressed per standard deviation (SD). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional or unconditional logistic regression and pooled using fixed-effects meta-analysis. Subgroup analyses were conducted by age at blood draw, time from blood sample to diagnosis, oestrogen receptor-positivity status and tumour stage.ResultsNone of the measures of epigenetic aging were associated with risk of breast cancer in the pooled analysis: Horvath ‘age acceleration’ (AA): OR per SD = 1.02, 95%CI: 0.95–1.10; AA-Hannum: OR = 1.03, 95%CI:0.95–1.12; PhenoAge: OR = 1.01, 95%CI: 0.94–1.09 and GrimAge: OR = 1.03, 95%CI: 0.94–1.12, in models adjusting for white blood cell proportions, body mass index, smoking and alcohol consumption. The BMI-adjusted predictor of BMI was associated with breast cancer risk, OR per SD = 1.09, 95%CI: 1.01–1.17. The results for the alcohol and smoking methylation-based predictors were consistent with a null association. Risk did no
van Roekel EH, Bours MJL, Breukink SO, et al., 2022, Longitudinal associations of plasma metabolites with persistent fatigue among colorectal cancer survivors up to 2 years after treatment, INTERNATIONAL JOURNAL OF CANCER, Vol: 152, Pages: 214-226, ISSN: 0020-7136
Roscoe C, Mackay C, Gulliver J, et al., 2022, Associations of private residential gardens versus other greenspace types with cardiovascular and respiratory disease mortality: observational evidence from UK Biobank, Environment International, Vol: 167, ISSN: 0160-4120
BackgroundLongitudinal evidence linking urban greenspace to reduced rates of all-cause and cause-specific mortality has mostly been established using greenness measures of limited specificity such as vegetation indices. Evidence on specific green space types, including private residential gardens is less well established.MethodsWe examined associations of greenspace with all-cause, non-injury, cardiovascular disease (CVD) and respiratory disease deaths in UK Biobank – a national prospective cohort of adults with linked Office for National Statistics mortality records. We included private residential gardens and other greenspace types e.g. public parks, sport facilities, using categories from Ordnance Survey MasterMap™ Greenspace. We used Cox proportional hazards models, adjusted for individual and area-level covariates, and stratified analyses by sex, household income, and area-level deprivation. In sensitivity analyses, we further adjusted for air pollution, road-traffic noise, indirect tobacco smoke exposure, and physical activity, and restricted analyses to non-movers.ResultsIn 232,926 participants, we observed 13,586 all-cause, 13,159 non-injury, 2,796 cardiovascular (CVD), and 968 respiratory disease deaths. Private residential garden cover showed inverse associations with all-cause, non-injury, CVD, and chronic respiratory disease mortality, after adjustment for covariates and other types of greenspace, with hazard ratios and 95% confidence intervals of 0.94 (0.91, 0.97), 0.95 (0.92, 0.97), 0.92 (0.86, 0.98) and 0.87 (0.78, 0.98), respectively, per interquartile range (IQR) increase in private residential garden cover (IQR = 21.6% increase within 100 m buffer). Other greenspace types showed weaker inverse associations with CVD and chronic respiratory disease mortality than private residential gardens. Sex, household income, and area level deprivation modified associations. Findings were robust to sensitivity analyses.ConclusionOur finding that priv
Kenkhuis M-F, Klingestijn M, Fanshawe A-M, et al., 2022, Longitudinal associations of sedentary behavior and physical activity with body composition in colorectal cancer survivors up to 2 years post treatment, JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, ISSN: 0171-5216
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