Imperial College London

DrKostasTsilidis

Faculty of MedicineSchool of Public Health

Reader in Cancer Epidemiology and Prevention
 
 
 
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+44 (0)20 7594 2623k.tsilidis

 
 
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Location

 

School of Public HealthWhite City Campus

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Summary

 

Publications

Publication Type
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364 results found

Tsilidis KK, Cariolou M, Becerra-Tomas N, Balducci K, Vieira R, Abar L, Aune D, Markozannes G, Nanu N, Greenwood DC, Giovannucci EL, Gunter MJ, Jackson AA, Kampman E, Lund V, Allen K, Brockton NT, Croker H, Katsikioti D, McGinley-Gieser D, Mitrou P, Wiseman M, Cross AJ, Riboli E, Clinton SK, McTiernan A, Norat T, Chan DSMet al., 2023, Postdiagnosis body fatness, recreational physical activity, dietary factors and breast cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading, International Journal of Cancer, Vol: 152, Pages: 635-644, ISSN: 0020-7136

Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta-analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random-effects meta-analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all-cause mortality (RR per 5 kg/m2 in body mass index: 1.07, 95% CI: 1.05-1.10), breast cancer-specific mortality (RR: 1.10, 95% CI: 1.06-1.14) and second primary breast cancer (RR: 1.14, 95% CI: 1.04-1.26) was graded as strong (likelihood of causality: probable). The evidence for body fatness and breast cancer recurrence and other nonbreast cancer-related mortality was graded as limited (likelihood of causality: limited-suggestive). The evidence on recreational physical activity and lower risk of all-cause (RR per 10 metabolic equivalent of task-hour/week: 0.85, 95% CI: 0.78-0.92) and breast cancer-specific mortality (RR: 0.86, 95% CI: 0.77-0.96) was judged as limited-suggestive. Data on dietary factors was limited, and no conclusions could be reached except for healthy dietary patterns, isoflavone and dietary fibre intake and serum 25(OH)D concentrations that were graded with limited-suggestive evidence for lower risk of the examined outcomes. Our results encourage the development of lifestyle recommendations for breast cancer patients to avoid obesity and be physically active.

Journal article

Chan DSM, Vieira R, Abar L, Aune D, Balducci K, Cariolou M, Greenwood DC, Markozannes G, Nanu N, Becerra-Tomas N, Giovannucci EL, Gunter MJ, Jackson AA, Kampman E, Lund V, Allen K, Brockton NT, Croker H, Katsikioti D, McGinley-Gieser D, Mitrou P, Wiseman M, Cross AJ, Riboli E, Clinton SK, McTiernan A, Norat T, Tsilidis KKet al., 2023, Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta-analysis, International Journal of Cancer, Vol: 152, Pages: 572-599, ISSN: 0020-7136

Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited-suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist-hip-ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random-effects meta-analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre-defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all-cause mortality (64 studies, 32 507 deaths), breast cancer-specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m2 BMI were 1.07 (1.05-1.10), 1.10 (1.06-1.14) and 1.14 (1.04-1.26), with high between-study heterogeneity (I2 = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist-hip-ratio and all-cause and breast cancer-specific mortality. There was limited-suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited-no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease-free-survival, but more intervention trials and well-designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes.

Journal article

Huang J, Su B, Karhunen V, Gill D, Zuber V, Ahola-Olli A, Palaniswamy S, Auvinen J, Herzig K-H, Keinänen-Kiukaanniemi S, Salmi M, Jalkanen S, Lehtimäki T, Salomaa V, Raitakari OT, Matthews PM, Elliott P, Tsilidis KK, Jarvelin M-R, Tzoulaki I, Dehghan Aet al., 2023, Inflammatory diseases, inflammatory biomarkers, and Alzheimer disease: an observational analysis and mendelian randomization, Neurology, Vol: 100, Pages: e568-e581, ISSN: 0028-3878

OBJECTIVES: Whether chronic autoimmune inflammatory diseases causally affect the risk of AD is controversial. We characterised the relationship between inflammatory diseases and the risk of AD and explore the role of circulating inflammatory biomarkers in the relationships between inflammatory diseases and AD. METHODS: We performed observational analyses for chronic autoimmune inflammatory diseases and risk of AD using data from 2,047,513 participants identified in the UK Clinical Practice Research Datalink (CPRD). Using data of a total of more than 1,100,000 individuals from 15 large scale genome-wide association study (GWAS) datasets, we performed two-sample Mendelian randomisation (MR) to investigate the relationships between chronic autoimmune inflammatory diseases, circulating inflammatory biomarker levels, and risk of AD. RESULTS: Cox regression models using CPRD data showed that overall incidence of AD was higher among patients with inflammatory bowel disease (IBD) (hazard ratio (HR)=1.17; 95%CI 1.15 to 1.19; P-value=2.1×10-4), other inflammatory polyarthropathies & systematic connective tissue disorders (OID) (HR=1.13; 95%CI 1.12 to 1.14; P-value=8.6×10-5), psoriasis (HR=1.13; 95%CI 1.10 to 1.16; P-value=2.6×10-4), rheumatoid arthritis (RA) (HR=1.08; 95%CI 1.06 to 1.11; P-value=4.0×10-4), and multiple sclerosis (MS) (HR=1.06; 95%CI 1.04 to 1.07; P-value=2.8×10-4) compared to the age (± 5 years) and sex-matched comparison groups free from all inflammatory diseases under investigation. Bidirectional MR analysis identified relationships between chronic autoimmune inflammatory diseases and circulating inflammatory biomarkers. Particularly, circulating monokine induced by gamma interferon (MIG) level was suggestively associated with a higher risk of AD (odds ratio from inverse variance weighted (ORIVW)=1.23; 95%CI 1.06 to 1.42; PIVW=0.007), and lower risk of Crohn's disease (ORIVW=0.73; 95%CI -0.62, 0.86; PIVW=1.3×10

Journal article

Rizos E, Kanellopoulou A, Filis P, Markozannes G, Chaliasos K, Ntzani E, Tzamouranou A, Tentolouris N, Tsilidis Ket al., 2023, DIFFERENCE ON GLUCOSE PROFILE FROM CONTINUOUS GLUCOSE MONITORING (CGM) IN PREDIABETIC VS NORMOGLYCAEMIC INDIVIDUALS: A MATCHED-PAIR ANALYSIS, Publisher: MARY ANN LIEBERT, INC, Pages: A198-A198, ISSN: 1520-9156

Conference paper

Papandreou C, Papagiannopoulos C, Koutsonida M, Kanellopoulou A, Markozannes G, Polychronidis G, Tzakos AG, Fragkiadakis GA, Evangelou E, Ntzani E, Tzoulaki I, Aretouli E, Tsilidis KKet al., 2023, Mediterranean diet related metabolite profiles and cognitive performance., Clinical Nutrition, Vol: 42, Pages: 173-181, ISSN: 0261-5614

BACKGROUND & AIMS: Evidence suggests that adherence to the Mediterranean diet (MedDiet) affects human metabolism and may contribute to better cognitive performance. However, the underlying mechanisms are not clear. OBJECTIVE: We generated a metabolite profile for adherence to MedDiet and evaluated its cross-sectional association with aspects of cognitive performance. METHODS: A total of 1250 healthy Greek middle-aged adults from the Epirus Health Study cohort were included in the analysis. Adherence to the MedDiet was assessed using the 14-point Mediterranean Diet Adherence Screener (MEDAS); cognition was measured using the Trail Making Test, the Verbal Fluency test and the Logical Memory test. A targeted metabolite profiling (n = 250 metabolites) approach was applied, using a high-throughput nuclear magnetic resonance platform. We used elastic net regularized regressions, with a 10-fold cross-validation procedure, to identify a metabolite profile for MEDAS. We evaluated the associations of the identified metabolite profile and MEDAS with cognitive tests, using multivariable linear regression models. RESULTS: We identified a metabolite profile composed of 42 metabolites, mainly lipoprotein subclasses and fatty acids, significantly correlated with MedDiet adherence (Pearson r = 0.35, P-value = 5.5 × 10-37). After adjusting for known risk factors and accounting for multiple testing, the metabolite profile and MEDAS were not associated with the cognitive tests. CONCLUSIONS: A plasma metabolite profile related to better adherence to the MedDiet was not associated with the tested aspects of cognitive performance, in a middle-aged Mediterranean population.

Journal article

Murphy N, Newton CC, Song M, Papadimitriou N, Hoffmeister M, Phipps AI, Harrison TA, Newcomb PA, Aglago EK, Berndt SI, Brenner H, Buchanan DD, Cao Y, Chan AT, Chen X, Cheng I, Chang-Claude J, Dimou N, Drew D, Farris AB, French AJ, Gallinger S, Georgeson P, Giannakis M, Giles GG, Gruber SB, Harlid S, Hsu L, Huang W-Y, Jenkins MA, Laskar RS, Le Marchand L, Limburg P, Lin Y, Mandic M, Nowak JA, Obón-Santacana M, Ogino S, Qu C, Sakoda LC, Schoen RE, Southey MC, Stadler ZK, Steinfelder RS, Sun W, Thibodeau SN, Toland AE, Trinh QM, Tsilidis KK, Ugai T, Van Guelpen B, Wang X, Woods MO, Zaidi SH, Gunter MJ, Peters U, Campbell PTet al., 2023, Body mass index and molecular subtypes of colorectal cancer, Journal of the National Cancer Institute, Vol: 115, Pages: 165-173, ISSN: 0027-8874

BACKGROUND: Obesity is an established risk factor for colorectal cancer (CRC), but the evidence for the association is inconsistent across molecular subtypes of the disease. METHODS: We pooled data on body mass index (BMI), tumor microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, and Jass classification types for 11 872 CRC cases and 11 013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for covariables. RESULTS: Higher BMI was associated with increased CRC risk (OR per 5 kg/m2 = 1.18, 95% CI = 1.15 to 1.22). The positive association was stronger for men than women but similar across tumor subtypes defined by individual molecular markers. In analyses by Jass type, higher BMI was associated with elevated CRC risk for types 1-4 cases but not for type 5 CRC cases (considered familial-like/Lynch syndrome microsatellite instability-H, CpG island methylator phenotype-low or negative, BRAF-wild type, KRAS-wild type, OR = 1.04, 95% CI = 0.90 to 1.20). This pattern of associations for BMI and Jass types was consistent by sex and design of contributing studies (cohort or case-control). CONCLUSIONS: In contrast to previous reports with fewer study participants, we found limited evidence of heterogeneity for the association between BMI and CRC risk according to molecular subtype, suggesting that obesity influences nearly all major pathways involved in colorectal carcinogenesis. The null association observed for the Jass type 5 suggests that BMI is not a risk factor for the development of CRC for individuals with Lynch syndrome.

Journal article

Al-Jafar R, Wahyuni NS, Belhaj K, Ersi MH, Boroghani Z, Alreshidi A, Alkhalaf Z, Elliott P, Tsilidis KK, Dehghan A, Al Jafar Ret al., 2023, The impact of Ramadan fasting on anthropometric measurements and body composition: evidence from London Ramadan Study and a meta-analysis, Frontiers in Nutrition, Vol: 10, Pages: 1-24, ISSN: 2296-861X

Background: Although the effect of Ramadan intermittent fasting (RIF) on anthropometry and body composition has been questioned, none of the previous studies tried to explain the reported changes in these parameters. Also, systematic reviews that investigated the topic were limited to healthy individuals or a specific disease group.Methods: The London Ramadan Study (LORANS) is an observational study on health effects of RIF. We measured weight, waist circumference (WC), hip circumference (HC), body mass index (BMI), waist-to-hip ratio (WHR), basal metabolic rate (BMR), fat percentage (FP), free-fat mass (FFM), extremities predicted muscle mass, total body water (TBW), trunk FM, trunk FFM and trunk predicted muscle mass before and immediately after Ramadan. Using mixed-effects regression models, we investigated the effect of RIF with adjustment for potential confounders. We also conducted a meta-analysis of the results of LORANS with other studies that investigated the effect of RIF on anthropometry and body composition. The review protocol is registered with PROSPERO registry (CRD42020186532).Results: We recruited 146 participants (Mean ± SD age = 43.3 ± 15 years). Immediately after Ramadan, compared with before Ramadan, the mean difference was−1.6 kg (P<0.01) in weight,−1.95cm (P<0.01) in WC,−2.86cm (P <0.01) in HC, −0.60 kg/m2 (P < 0.01) in BMI and −1.24 kg (P < 0.01) in FM. In the systematic review and meta-analysis, after screening 2,150 titles and abstracts, 66 studies comprising 7,611 participants were included. In the general population, RIF was followed by a reduction of 1.12 Kg in body weight (−1.89– −0.36, I2 = 0), 0.74 kg/m2 reduction in BMI (−0.96– −0.53, I2 = 0), 1.54cm reduction in WC (−2.37– −0.71, I2 = 0) and 1.76cm reduction in HC (−2.69– −0.83, I2 = 0). The effect of fasting on anthropometric and body composition parame

Journal article

Papadimitriou N, Bull CJ, Jenab M, Hughes DJ, Bell JA, Sanderson E, Timpson NJ, Smith GD, Albanes D, Campbell PT, Küry S, Le Marchand L, Ulrich CM, Visvanathan K, Figueiredo JC, Newcomb PA, Pai RK, Peters U, Tsilidis KK, Boer JMA, Vincent EE, Mariosa D, Gunter MJ, Richardson TG, Murphy Net al., 2023, Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study, BMC Medicine, Vol: 21, Pages: 1-10, ISSN: 1741-7015

BACKGROUND: Observational studies have linked childhood obesity with elevated risk of colorectal cancer; however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colorectal cancer risk. METHODS: We conducted Mendelian randomization (MR) analyses to investigate potential causal relationships between self-perceived body size (thinner, plumper, or about average) in early life (age 10) and measured body mass index in adulthood (mean age 56.5) with risk of colorectal cancer. The total and independent effects of body size exposures were estimated using univariable and multivariable MR, respectively. Summary data were obtained from a genome-wide association study of 453,169 participants in UK Biobank for body size and from a genome-wide association study meta-analysis of three colorectal cancer consortia of 125,478 participants. RESULTS: Genetically predicted early life body size was estimated to increase odds of colorectal cancer (odds ratio [OR] per category change: 1.12, 95% confidence interval [CI]: 0.98-1.27), with stronger results for colon cancer (OR: 1.16, 95% CI: 1.00-1.35), and distal colon cancer (OR: 1.25, 95% CI: 1.04-1.51). After accounting for adult body size using multivariable MR, effect estimates for early life body size were attenuated towards the null for colorectal cancer (OR: 0.97, 95% CI: 0.77-1.22) and colon cancer (OR: 0.97, 95% CI: 0.76-1.25), while the estimate for distal colon cancer was of similar magnitude but more imprecise (OR: 1.27, 95% CI: 0.90-1.77). Genetically predicted adult life body size was estimated to increase odds of colorectal (OR: 1.27, 95% CI: 1.03, 1.57), colon (OR: 1.32, 95% CI: 1.05, 1.67), and proximal colon (OR: 1.57, 95% CI: 1.21, 2.05). CONCLUSIONS: Our findings suggest that the positive association between early life body size and colorectal cancer risk is likely due to large body size retainment into adulthood.

Journal article

Fernandez-Rozadilla C, Timofeeva M, Chen Z, Law P, Thomas M, Bien S, Diez-Obrero V, Li L, Fernandez-Tajes J, Palles C, Sherwood K, Harris S, Svinti V, McDonnell K, Farrington S, Studd J, Vaughan-Shaw P, Shu X-O, Long J, Cai Q, Guo X, Lu Y, Scacheri P, Studd J, Huyghe J, Harrison T, Shibata D, Haiman C, Devall M, Schumacher F, Melas M, Rennert G, Obon-Santacana M, Martin-Sanchez V, Moratalla-Navarro F, Oh JH, Kim J, Jee SH, Jung KJ, Kweon S-S, Shin M-H, Shin A, Ahn Y-O, Kim D-H, Oze I, Wen W, Matsuo K, Matsuda K, Tanikawa C, Ren Z, Gao Y-T, Jia W-H, Potter J, Jenkins M, Win AK, Pai R, Figueiredo J, Haile R, Gallinger S, Woods M, Newcomb P, Shibata D, Cheadle J, Kaplan R, Maughan T, Kerr R, Kerr D, Kirac I, Boehm J, Mecklin L-P, Jousilahti P, Knekt P, Aaltonen L, Rissanen H, Pukkala E, Eriksson J, Cajuso T, Hanninen U, Kondelin J, Palin K, Tanskanen T, Renkonen-Sinisalo L, Zanke B, Mannisto S, Albanes D, Weinstein S, Ruiz-Narvaez E, Palmer J, Buchanan D, Platz E, Visvanathan K, Ulrich C, Siegel E, Brezina S, Gsur A, Campbell P, Chang-Claude J, Hoffmeister M, Brenner H, Slattery M, Potter J, Tsilidis K, Schulze M, Gunter M, Murphy N, Castells A, Castellvi-Bel S, Moreira L, Arndt V, Shcherbina A, Stern M, Pardamean B, Bishop T, Giles G, Southey M, Idos G, McDonnell K, Abu-Ful Z, Greenson J, Shulman K, Lejbkowicz F, Offit K, Su Y-R, Steinfelder R, Keku T, van Guelpen B, Hudson T, Hampel H, Pearlman R, Berndt S, Hayes R, Martinez ME, Thomas S, Corley D, Pharoah P, Larsson S, Yen Y, Lenz H-J, White E, Li L, Doheny K, Pugh E, Shelford T, Chan A, Cruz-Correa M, Lindblom A, Shibata D, Joshi A, Schafmayer C, Scacheri P, Kundaje A, Nickerson D, Schoen R, Hampe J, Stadler Z, Vodicka P, Vodickova L, Vymetalkova V, Papadopoulos N, Edlund C, Gauderman W, Thomas D, Shibata D, Toland A, Markowitz S, Kim A, Gruber S, van Duijnhoven F, Feskens E, Sakoda L, Gago-Dominguez M, Wolk A, Naccarati A, Pardini B, FitzGerald L, Lee SC, Ogino S, Bien S, Kooperberg C, Li C, Lin Y, Prentice R, Quet al., 2023, Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries, NATURE GENETICS, Vol: 55, Pages: 89-+, ISSN: 1061-4036

Journal article

Karhunen V, Gill D, Huang J, Bouras E, Malik R, Ponsford MJ, Ahola-Olli A, Papadopoulou A, Palaniswamy S, Sebert S, Wielscher M, Auvinen J, Veijola J, Herzig K-H, Timonen M, Keinänen-Kiukaanniemi S, Dichgans M, Salmi M, Jalkanen S, Lehtimäki T, Salomaa V, Raitakari O, Jones SA, Hovingh GK, Tsilidis KK, Järvelin M-R, Dehghan Aet al., 2023, The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study., BMJ Med, Vol: 2

OBJECTIVE: To leverage large scale genetic association data to investigate the interplay between circulating cytokines and cardiometabolic traits, and thus identifying potential therapeutic targets. DESIGN: Bi-directional Mendelian randomisation study. SETTING: Genome-wide association studies from three Finnish cohorts (Northern Finland Birth Cohort 1966, Young Finns Study, or FINRISK study), and genetic association summary statistics pooled from observational studies for expression quantitative trait loci and cardiometabolic traits. PARTICIPANTS: Data for 47 circulating cytokines in 13 365 individuals from genome-wide association studies, summary statistic data for up to 21 735 individuals on circulating cytokines, summary statistic gene expression data across 49 tissues in 838 individuals, and summary statistic data for up to 1 320 016 individuals on cardiometabolic traits. INTERVENTIONS: Relations between circulating cytokines and cardiovascular, anthropometric, lipid, or glycaemic traits (coronary artery disease, stroke, type 2 diabetes mellitus, body mass index, waist circumference, waist to hip ratio, systolic blood pressure, glycated haemoglobin, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, triglycerides, C reactive protein, glucose, fasting insulin, and lifetime smoking). MAIN OUTCOME METHODS: Genetic instrumental variables that are biologically plausible for the circulating cytokines were generated. The effects of cardiometabolic risk factors on concentrations of circulating cytokines, circulating cytokines on other circulating cytokines, and circulating cytokines on cardiometabolic outcomes were investigated. RESULTS: Genetic evidence (mendelian randomisation P<0.0011) suggests that higher body mass index, waist circumference, smoking, higher concentrations of lipids, and systolic blood pressure increase circulating concentrations of several inflammatory cytokines and C reactive protein. Evi

Journal article

Lopez DS, Taha S, Gutierrez S, Villasante-Tezanos A, Khalife WI, Alzweri L, Markides K, Baillargeon J, Tsilidis KKet al., 2022, Association of total and free testosterone with cardiovascular disease in a nationally representative sample of white, black, and Mexican American men, International Journal of Impotence Research, Pages: 1-9, ISSN: 0955-9930

Associations of total testosterone (T) and calculated free T with cardiovascular disease (CVD) remain poorly understood. Particularly how these associations vary according to race and ethnicity in a nationally representative sample of men. Data included 7058 men (≥20 years) from NHANES. CVD was defined as any reported diagnosis of heart failure (HF), coronary artery disease (CAD), myocardial infarction (MI), and stroke. Total T (ng/mL) was obtained among males who participated in the morning examination. Weighted multivariable-adjusted logistic regression models were conducted. We found associations of low T (OR = 1.57, 95% CI = 1.17–2.11), low calculated free T (OR = 1.53, 95% CI = 1.10–2.17), total T (Q1 vs Q5), and calculated free T (Q1 vs Q5) with CVD after adjusting for estradiol and SHBG. In disease specific analysis, low T increased prevalence of MI (OR = 1.72, 95% CI = 1.08–2.75) and HF (OR = 1.74, 95% CI = 1.08–2.82), but a continuous increment of total T reduced the prevalence of CAD. Similar inverse associations were identified among White and Mexican Americans, but not Blacks (OR = 0.93, 95% CI = 0.49–1.76). Low levels of T and calculated free T were associated with an increased prevalence of overall CVD and among White and Mexican Americans. Associations remained in the same direction with specific CVD outcomes in the overall population.

Journal article

Zagkos L, Dib M-J, Pinto R, Gill D, Koskeridis F, Drenos F, Markozannes G, Elliott P, Zuber V, Tsilidis K, Dehghan A, Tzoulaki Iet al., 2022, Associations of genetically predicted fatty acid levels across the phenome: a mendelian randomisation study, PLoS Medicine, Vol: 19, ISSN: 1549-1277

BACKGROUND: Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes. METHODS AND FINDINGS: The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.

Journal article

Lopez DS, Malagaris I, Polychronopoulou E, Tsilidis KK, Milani SA, Peek MK, Villasante-Tezanos A, Alzweri L, Baillargeon J, Kuo Y-F, Canfield Set al., 2022, Metformin and testosterone replacement therapy inversely associated with hormone-associated cancers (prostate, colorectal and male breast cancers) among older White and Black men, CLINICAL ENDOCRINOLOGY, Vol: 97, Pages: 792-803, ISSN: 0300-0664

Journal article

Aune D, Markozannes G, Abar L, Balducci K, Cariolou M, Nanu N, Vieira R, Anifowoshe Y, Greenwood DC, Clinton S, Giovannucci EL, Gunter MJ, Jackson A, Kampman E, Lund V, McTiernan A, Riboli E, Allen K, Brockton NT, Croker H, Katsikioti D, McGinley-Gieser D, Mitrou P, Wiseman M, Velikova G, Demark-Wahnefried W, Norat T, Tsilidis KK, Chan DSMet al., 2022, Physical activity and health-related quality of life in women with breast cancer: a meta-analysis, JNCI Cancer Spectrum, Vol: 6, Pages: 1-14, ISSN: 2515-5091

Background: Physical activity (PA) is associated with improved health-related quality-of-life (HRQoL) among women with breast cancer; however, uncertainty remains regarding PA types and dose (frequency, duration, intensity) and various HRQoL measures. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to clarify whether specific types and doses of physical activity was related to global and specific domains of HRQoL, as part of the Global Cancer Update Programme, formerly known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project. Methods: PubMed and CENTRAL databases were searched up to August 31, 2019. Weighted mean differences (WMDs) in HRQoL scores were estimated using random effects models. An independent Expert Panel graded the evidence. Results: Seventy-nine RCTs (14,554 breast cancer patients) were included. PA interventions resulted in higher global HRQoL as measured by the Functional Assessment of Cancer Therapy-Breast, WMDs (95% confidence intervals)=5.94 (2.64-9.24, I2=59%, n=12), Functional Assessment of Cancer Therapy-General, 4.53 (1.94-7.13, I2=72%, n=18), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30, 6.78 (2.61-10.95, I2=76.3%, n=17). The likelihood of causality was considered probable that PA improves HRqoL in breast cancer survivors. Effects were weaker for physical function and mental/emotional health. Evidence regarding dose and type of PA remains insufficient for firm conclusions. Conclusion: PA results in improved global HRQoL in breast cancer survivors with weaker effects observed for physical function and mental/emotional health. Additional research is needed to define the impact of types and doses of activity on various domains of HRQoL.

Journal article

Tang SN, Zuber V, Tsilidis K, 2022, Identifying and ranking causal biochemical biomarkers for breast cancer: a Mendelian randomisation study, BMC Medicine, Vol: 20, Pages: 1-14, ISSN: 1741-7015

Background:Only a few of the 34 biochemical biomarkers measured in the UK Biobank (UKB) have been associated with breast cancer, with many associations suffering from possible confounding and reverse causation. This study aimed to screen and rank all UKB biochemical biomarkers for possible causal relationships with breast cancer.Methods:We conducted two-sample Mendelian randomisation (MR) analyses on ~420,000 women by leveraging summary-level genetic exposure associations from the UKB study (n = 194,174) and summary-level genetic outcome associations from the Breast Cancer Association Consortium (n = 228,951). Our exposures included all 34 biochemical biomarkers in the UKB, and our outcomes were overall, oestrogen-positive, and oestrogen-negative breast cancer. We performed inverse-variance weighted MR, weighted median MR, MR-Egger, and MR-PRESSO for 30 biomarkers for which we found multiple instrumental variables. We additionally performed multivariable MR to adjust for known risk factors, bidirectional MR to investigate reverse causation, and MR Bayesian model averaging to rank the significant biomarkers by their genetic evidence.Results:Increased genetic liability to overall breast cancer was robustly associated with the following biomarkers by decreasing importance: testosterone (odds ratio (OR): 1.12, 95% confidence interval (CI): 1.04–1.21), high-density lipoprotein (HDL) cholesterol (OR: 1.08, 95% CI: 1.04–1.13), insulin-like growth factor 1 (OR: 1.08, 95% CI: 1.02–1.13), and alkaline phosphatase (ALP) (OR: 0.93, 95% CI: 0.89–0.98).ConclusionsOur findings support a likely causal role of genetically predicted levels of testosterone, HDL cholesterol, and IGF-1, as well as a novel potential role of ALP in breast cancer aetiology. Further studies are needed to understand full disease pathways that may inform breast cancer prevention.

Journal article

Koutsonidia M, Markozannes G, Bouras E, Aretouli E, Tsilidis Ket al., 2022, Metabolic syndrome and cognition: A systematic review across cognitive domains and a bibliometric analysis, Frontiers in Psychology, Vol: 13, ISSN: 1664-1078

The aim of this review is to investigate the association between metabolic syndrome (MetS) and cognitive decline in distinct cognitive domains, and to perform a complementary study description through the bibliometric analysis. PubMed and Scopus databases were searched from inception to 15 December 2021 to identify longitudinal studies that examined the association of MetS with incident decline, in order to prevent reverse causality. The Preferred Reporting Items for Systematic Review and Meta-Analysis checklist was used to conduct the present systematic review. Thirty studies were included and results were analyzed across the cognitive domains of global cognition, memory, executive functions, attention, visuoconstructive abilities, and language. The majority of the studies reviewed did not report statistically significant results for most cognitive domains investigated, and decline in specific cognitive domains was not consistently associated with the presence of MetS. Meta-analyses were not conducted due to the high degree of between-study heterogeneity regarding the MetS definitions, the cognitive domains examined, the specific tests used for each cognitive domain and the different measures of association used. Bibliometric analysis revealed that most studies are conducted by research teams from USA and China, and that cognitive tasks that reflect real-life abilities are rarely examined. Future studies should employ larger sample sizes, longer follow-up periods, a global consensus for MetS definition and standardized tests of the above mentioned cognitive domains as well as problem-solving tasks with high sensitivity and specificity to clarify the impact of MetS on cognition and its underlying mechanisms.

Journal article

Breeur M, Ferrari P, Dossus L, Jenab M, Johansson M, Rinaldi S, Travis RC, His M, Key TJ, Schmidt JA, Overvad K, Tjønneland A, Kyrø C, Rothwell JA, Laouali N, Severi G, Kaaks R, Katzke V, Schulze MB, Eichelmann F, Palli D, Grioni S, Panico S, Tumino R, Sacerdote C, Bueno-de-Mesquita B, Olsen KS, Sandanger TM, Nøst TH, Quirós JR, Bonet C, Barranco MR, Chirlaque M-D, Ardanaz E, Sandsveden M, Manjer J, Vidman L, Rentoft M, Muller D, Tsilidis K, Heath AK, Keun H, Adamski J, Keski-Rahkonen P, Scalbert A, Gunter MJ, Viallon Vet al., 2022, Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition, BMC Medicine, Vol: 20, ISSN: 1741-7015

BACKGROUND: Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. METHODS: We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty. RESULTS: Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk. CONCLUSIONS: These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.

Journal article

Chalitsios CV, Tsilidis KK, Tzoulaki I, 2022, Psoriasis and COVID-19: A bidirectional Mendelian randomization study., Journal of the American Academy of Dermatology, ISSN: 0190-9622

Journal article

Botteri E, Peveri G, Berstad P, Bagnardi V, Chen SLF, Sandanger TM, Hoff G, Dahm CC, Antoniussen CS, Tjønneland A, Eriksen AK, Skeie G, Perez-Cornago A, Huerta JM, Jakszyn P, Harlid S, Sundström B, Barricarte A, Monninkhof EM, Derksen JWG, Schulze MB, Bueno-de-Mesquita B, Sánchez M-J, Cross AJ, Tsilidis KK, De Magistris MS, Kaaks R, Katzke V, Rothwell JA, Laouali N, Severi G, Amiano P, Contiero P, Sacerdote C, Goldberg M, Touvier M, Freisling H, Viallon V, Weiderpass E, Riboli E, Gunter MJ, Jenab M, Ferrari Pet al., 2022, Changes in lifestyle and risk of colorectal cancer in the European prospective investigation into cancer and nutrition., American Journal of Gastroenterology, Vol: 10, Pages: 1-10, ISSN: 0002-9270

INTRODUCTION: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multi-country European cohort. METHODS: We used baseline and follow-up questionnaire data from the EPIC cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index and physical activity collected at the two timepoints. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. Median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI>11), those in the bottom tertile at follow-up (HLI≤9) had a higher CRC risk (HR 1.34; 95%CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95%CI 0.59-1.00) than those remaining in the bottom tertile. DISCUSSION: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.

Journal article

Karalexi MA, Markozannes G, Tagkas CF, Katsimpris A, Tseretopoulou X, Tsilidis KK, Spector LG, Schuz J, Siahanidou T, Petridou ET, Ntzani EEet al., 2022, Nutritional status at diagnosis as predictor of survival from childhood cancer: a review of the literature, Diagnostics, Vol: 12, Pages: 1-13, ISSN: 2075-4418

Few studies so far have examined the impact of nutritional status on the survival of children with cancer, with the majority of them focusing on hematological malignancies. We summarized published evidence reporting the association of nutritional status at diagnosis with overall survival (OS), event-free survival (EFS), relapse, and treatment-related toxicity (TRT) in children with cancer. Published studies on children with leukemia, lymphoma, and other solid tumors have shown that both under-nourished and over-nourished children at cancer diagnosis had worse OS and EFS. Particularly, the risk of death and relapse increased by 30–50% among children with leukemia with increased body mass index at diagnosis. Likewise, the risk of TRT was higher among malnourished children with osteosarcoma and Ewing sarcoma. Nutritional status seems to play a crucial role in clinical outcomes of children with cancer, thus providing a significant modifiable prognostic tool in childhood cancer management. Future studies with adequate power and longitudinal design are needed to further evaluate the association of nutritional status with childhood cancer outcomes using a more standardized definition to measure nutritional status in this population. The use of new technologies is expected to shed further light on this understudied area and give room to person-targeted intervention strategies.

Journal article

Yarmolinsky J, Robinson J, Tsilidis KK, Dehghan A, Johansson M, Mariosa D, Gunter MJ, Kiemeney LA, Smith GD, Martin RMet al., 2022, Using Human Genetics to Evaluate the Causal Role of Circulating Inflammatory Markers in Risk of Adult Cancer, Publisher: WILEY, Pages: 547-547, ISSN: 0741-0395

Conference paper

Georgiou AN, Zagkos L, Xu W, Wang L, Markozannes G, Loizidou EM, Theodoratou E, Evangelou E, Tsilidis KK, Tzoulaki Iet al., 2022, Appraising the causal role of risk factors in coronary artery disease and stroke: a systematic review of Mendelian randomization studies, International Genetic Epidemiology Society (IGES 2022) 31st Annual Meeting, Publisher: Wiley, Pages: 495-495, ISSN: 0741-0395

Conference paper

Tsilidis K, 2022, Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for the management of primary advanced and recurrent ovarian cancer: a systematic review and meta-analysis of randomized trials, ESMO Open, Vol: 7, Pages: 1-10, ISSN: 2059-7029

Introduction: Ovarian cancer is the most lethal gynecologic malignancy. Although treatment with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results, its role remains elusive. Aim: To assess the comprehensive randomized evidence for the use vs non-use of HIPEC in primary (POC) and recurrent (ROC) ovarian cancer.Materials and Methods: The Medline, Embase and Cochrane databases, as well as the ESMO and ASCO conference abstracts of the last 5 years, were scrutinized in January 2022 for randomized controlled trials (RCTs) that studied the use of HIPEC in ovarian cancer. Overall survival (OS), disease- and progression-free survival (DFS/PFS), as well as postoperative morbidity were the outcomes of interest. This study was reported in accordance to the PRISMA reporting guideline.Results: Six RCTs that randomized 737 patients were included in our analysis, of these four studies (519 patients) pertained primary and two (218 patients) recurrent settings. In primary ovarian cancer, the combination of HIPEC with interval cytoreductive surgery (CRS) and neoadjuvant chemotherapy significantly improved the 5-year OS (393 patients, RR=0.77; 95%CI: 0.67-0.90; p-value=0.001) and DFS (HR=0.60; 95%CI: 0.41-0.87; p-value=0.008) compared with standard treatment alone. In the absence of neoadjuvant chemotherapy the use of HIPEC+CRS was not associated to any survival advantage (126 patients, 4-year OS, RR=0.93; 95% CI: 0.57-1.53; p-value=0.781), but the sample size was smaller in this subset. Use of HIPEC in recurrent ovarian cancer did not provide any survival advantage (5-years OS: 218 patients, RR=0.85; 95% CI= 0.45-1.62; p-value=0.626). The risk for grade≥3 adverse events was similar between HIPEC and no HIPEC (RR=1.08; 95%CI: 0.98-1.18; p-value=0.109).Conclusion: In primary ovarian cancer the combination of HIPEC with interval cytoreductive surgery and neoadjuvant chemotherapy is a safe option that significantly improved 5-year OS and DFS. Its use in other

Journal article

Rizos EC, Kanellopoulou A, Filis P, Markozannes G, Chaliasos K, Ntzani EE, Tzamouranou A, Tentolouris N, Tsilidis KKet al., 2022, Difference on Glucose Profile From Continuous Glucose Monitoring in People With Prediabetes vs. Normoglycemic Individuals: A Matched-Pair Analysis, JOURNAL OF DIABETES SCIENCE AND TECHNOLOGY, ISSN: 1932-2968

Journal article

Lopez DS, Lee W-C, Garcia CO, Downer PB, Taha S, Villasante-Tezanos A, Tsilidis KK, Peek K, Kyriakos M, Canfield Set al., 2022, Low testosterone and high cholesterol levels in relation to all-cause, cardiovascular disease, and cancer mortality in White, Black, and Hispanic men: NHANES 1988-2015, HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM, Vol: 21, Pages: 399-411, ISSN: 1109-3099

Journal article

Mauri D, Filis P, Markozannes G, Filis N, Tsilidis Ket al., 2022, Hyperthermic intraperitoneal chemotherapy (HIPEC) for the management of primary advanced and recurrent ovarian cancer: A systematic review and meta-analysis of randomized trials, Annual Meeting of the European-Society-for-Medical-Oncology (ESMO), Publisher: ELSEVIER, Pages: S794-S794, ISSN: 0923-7534

Conference paper

Rapti I, Asimakopoulos A, Liontos A, Kosmidou M, Christaki E, Biros D, Milionis O, Tsourlos S, Ntotsikas E, Ntzani E, Evangelou E, Gartzonika K, Georgiou I, Tzoulaki I, Tsilidis K, Milionis Het al., 2022, Association of patient characteristics with clinical outcomes in a cohort of hospitalised patients with SARS-CoV-2 infection in a Greek referral centre for COVID-19, Epidemiology and Infection, Vol: 150, Pages: 1-9, ISSN: 0950-2688

Patient-important outcomes related to coronavirus disease 2019 (COVID-19) continue to drive the pandemic response across the globe. Various prognostic factors for COVID-19 severity have emerged and their replication across different clinical settings providing health services is ongoing. We aimed to describe the clinical characteristics and their association with outcomes in patients hospitalised with COVID-19 in the University Hospital of Ioannina. We assessed a cohort of 681 consecutively hospitalised patients with COVID-19 from January 2020 to December 2021. Demographic data, underlying comorbidities, clinical presentation, biochemical markers, radiologic findings, COVID-19 treatment and outcome data were collected at the first day of hospitalisation and up to 90 days. Multivariable Cox regression analyses were performed to investigate the associations between clinical characteristics (hazard ratios (HRs) per standard deviation (S.D.)) with intubation and/or mortality status. The participants' mean age was 62.8 (S.D., 16.9) years and 57% were males. The most common comorbidities were hypertension (45%), cardiovascular disease (19%) and diabetes mellitus (21%). Patients usually presented with fever (81%), cough (50%) and dyspnoea (27%), while lymphopenia and increased inflammatory markers were the most common laboratory abnormalities. Overall, 55 patients (8%) were intubated, and 86 patients (13%) died. There were statistically significant positive associations between intubation or death with age (HR: 2.59; 95% CI 1.52–4.40), lactate dehydrogenase (HR: 1.44; 95% CI 1.04–1.98), pO2/FiO2 ratio < 100 mmHg (HR: 3.52; 95% CI 1.14–10.84), and inverse association with absolute lymphocyte count (HR: 0.54; 95% CI 0.33–0.87). These data might help to identify points for improvement in the management of COVID-19 patients.

Journal article

Grenville ZS, Noor U, His M, Viallon V, Rinaldi S, Aglago EK, Amiano P, Brunkwall L, Chirlaque MD, Drake I, Eichelmann F, Freisling H, Grioni S, Heath AK, Kaaks R, Katzke V, Mayén-Chacon A-L, Milani L, Moreno-Iribas C, Pala V, Olsen A, Sánchez M-J, Schulze MB, Tjønneland A, Tsilidis KK, Weiderpass E, Winkvist A, Zamora-Ros R, Key TJ, Smith-Byrne K, Travis RC, Schmidt JAet al., 2022, Diet and BMI correlate with metabolite patterns associated with aggressive prostate cancer, Nutrients, Vol: 14, Pages: 3306-3306, ISSN: 2072-6643

Three metabolite patterns have previously shown prospective inverse associations with the risk of aggressive prostate cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC). Here, we investigated dietary and lifestyle correlates of these three prostate cancer-related metabolite patterns, which included: 64 phosphatidylcholines and three hydroxysphingomyelins (Pattern 1), acylcarnitines C18:1 and C18:2, glutamate, ornithine, and taurine (Pattern 2), and 8 lysophosphatidylcholines (Pattern 3). In a two-stage cross-sectional discovery (n = 2524) and validation (n = 518) design containing 3042 men free of cancer in EPIC, we estimated the associations of 24 dietary and lifestyle variables with each pattern and the contributing individual metabolites. Associations statistically significant after both correction for multiple testing (False Discovery Rate = 0.05) in the discovery set and at p < 0.05 in the validation set were considered robust. Intakes of alcohol, total fish products, and its subsets total fish and lean fish were positively associated with Pattern 1. Body mass index (BMI) was positively associated with Pattern 2, which appeared to be driven by a strong positive BMI-glutamate association. Finally, both BMI and fatty fish were inversely associated with Pattern 3. In conclusion, these results indicate associations of fish and its subtypes, alcohol, and BMI with metabolite patterns that are inversely associated with risk of aggressive prostate cancer

Journal article

Heath AK, Muller DC, van den Brandt PA, Critselis E, Gunter M, Vineis P, Weiderpass E, Boeing H, Ferrari P, Merritt MA, Rostgaard-Hansen AL, Tjonneland A, Overvad K, Katzke V, Srour B, Masala G, Sacerdote C, Ricceri F, Pasanisi F, Bueno-de-Mesquita B, Downward GS, Skeie G, Sandanger TM, Crous-Bou M, Rodriguez-Barranco M, Amiano P, Huerta JM, Ardanaz E, Drake I, Johansson M, Johansson I, Key T, Papadimitriou N, Riboli E, Tzoulaki I, Tsilidis KKet al., 2022, Diet-wide association study of 92 foods and nutrients and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study, International Journal of Cancer, Vol: 151, Pages: 1935-1946, ISSN: 0020-7136

Diet-wide association study of 92 foods and nutrients and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study

Journal article

Lopez DS, Kim H, Polychronopoulou E, Taha S, Tsilidis KK, Villasante-Tezanos A, Peek MK, Gilani S, Khera M, Baillargeon J, Kuo Y-F, Canfield Set al., 2022, Joint association of statins and testosterone replacement therapy with cardiovascular disease among older men with prostate cancer: SEER-Medicare 2007-2015, Cancer Epidemiology: the international journal of cancer epidemiology, detection and prevention, Vol: 79, ISSN: 0361-090X

BACKGROUND: Use of statins and testosterone replacement therapy (TTh) have been independently linked with prostate cancer (PCa) and cardiovascular diseases (CVD). However, there is a research gap about the joint association of statins and TTh with CVD among PCa survivors and a matched cancer-free cohort. METHODS: In SEER-Medicare 2007-2015 (N = 35,990 men), we identified 17,995 PCa survivors, and 17,995 age- and index-matched cancer-free men. Pre-diagnostic prescription of statins and TTh was ascertained for this analysis and examined in two matched cohorts. Weighted multivariable-adjusted conditional logistic regression models were used to evaluate the independent and joint associations of statins and TTh with CVD. RESULTS: We found that independently statins (OR = 0.48, 95% CI: 0.44-0.53) and TTh (OR = 0.74, 95% CI: 0.0.61-0.90) were each inversely associated with CVD in the overall sample. TTh plus statins was inversely associated with CVD (OR = 0.50, 95% CI: 0.36-0.70, Pinteraction = 0.03). Similar associations were observed among the matched cancer-free cohort. Among PCa survivors, only statins (OR = 0.62, 95% CI: 0.56-0.68) and combination of TTh plus statins (OR = 0.63, 95% CI: 0.44-0.90) were inversely associated with CVD, but not the independent use of TTh. CONCLUSION: Pre-diagnostic use of statins and TTh, independent or in combination, were inversely associated with CVD in the overall and cancer-free populations, but among PCa survivors it was mainly use of statins, not TTh. Greater reduced effects on CVD were observed with statins or in combination with statins, but not with TTh. Future studies need to confirm these associations among older men with aggressive PCa.

Journal article

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