Imperial College London

DrKostasTsilidis

Faculty of MedicineSchool of Public Health

Reader in Cancer Epidemiology and Prevention
 
 
 
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Contact

 

+44 (0)20 7594 2623k.tsilidis

 
 
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Location

 

Praed StreetSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

243 results found

Tsilidis K, 2022, Circulating inflammatory cytokines and risk of five cancers: a mendelian randomization analysis, BMC Medicine, Vol: 20, ISSN: 1741-7015

Background: Epidemiological and experimental evidence has linked chronic inflammation to cancer etiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically-predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomization (MR) analysis.Methods: Up to 31,112 individuals of European descent were included in genome-wide association study (GWAS) meta-analyses of 47 circulating cytokines. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene (cis), were used as instrumental variables. Inverse-variance weighted MR was used as the primary analysis, and the MR assumptions were evaluated in sensitivity and colocalization analyses and a false discovery rate (FDR) correction for multiple comparisons was applied. Corresponding germline GWAS summary data for five cancer outcomes (breast, endometrial, lung, ovarian and prostate) and their subtypes were selected from the largest cancer-specific GWASs available (cases ranging from 12 906 for endometrial to 133 384 for breast cancer). Results: There was evidence of inverse associations of macrophage migration inhibitory factor with breast cancer (OR per SD = 0.88, 95%CI: 0.83 to 0.94), interleukin-1 receptor antagonist with endometrial cancer (0.86, 0.80 to 0.93), interleukin-18 with lung cancer (0.87, 0.81 to 0.93), and beta-chemokine-RANTES with ovarian cancer (0.70, 0.57 to 0.85); and positive associations of monokine induced by gamma interferon with endometrial cancer (3.73, 1.86 to 7.47) and cutaneous T-cell attracting chemokine with lung cancer (1.51, 1.22 to 1.87). These associations were similar in sensitivity analyses and supported in colocalization analyses. Conclusions: Our study adds to current knowledge on the role of specific inflammatory biomarker pathways in cancer etiology. Further va

Journal article

Lopez DS, Liu L, Smith-Warner SA, Tsilidis KK, Daniel C, Baillargeon J, Rohrmann S, Platz EA, Giovannucci Eet al., 2022, Association of Prudent, Western, and Alternate Healthy Eating Index (AHEI-2010) dietary patterns with serum testosterone and sex hormone binding globulin levels in men, HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM, ISSN: 1109-3099

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Tsilidis K, 2022, Systematic review of Mendelian randomization studies on risk of cancer, BMC Medicine, ISSN: 1741-7015

Journal article

Ellingjord-Dale M, Christakoudi S, Weiderpass E, Panico S, Dossus L, Olsen A, Tjønneland A, Kaaks R, Schulze MB, Masala G, Gram IT, Skeie G, Rosendahl AH, Sund M, Key T, Ferrari P, Gunter M, Heath AK, Tsilidis KK, Riboli E, additional authorset al., 2022, Long-term weight change and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study., Int J Epidemiol, Vol: 50, Pages: 1914-1926

BACKGROUND: The role of obesity and weight change in breast-cancer development is complex and incompletely understood. We investigated long-term weight change and breast-cancer risk by body mass index (BMI) at age 20 years, menopausal status, hormone replacement therapy (HRT) and hormone-receptor status. METHODS: Using data on weight collected at three different time points from women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the association between weight change from age 20 years until middle adulthood and risk of breast cancer. RESULTS: In total, 150 257 women with a median age of 51 years at cohort entry were followed for an average of 14 years (standard deviation = 3.9) during which 6532 breast-cancer cases occurred. Compared with women with stable weight (±2.5 kg), long-term weight gain >10 kg was positively associated with postmenopausal breast-cancer risk in women who were lean at age 20 [hazard ratio (HR) = 1.42; 95% confidence interval 1.22-1.65] in ever HRT users (HR = 1.23; 1.04-1.44), in never HRT users (HR = 1.40; 1.16-1.68) and in oestrogen-and-progesterone-receptor-positive (ER+PR+) breast cancer (HR = 1.46; 1.15-1.85). CONCLUSION: Long-term weight gain was positively associated with postmenopausal breast cancer in women who were lean at age 20, both in HRT ever users and non-users, and hormone-receptor-positive breast cancer.

Journal article

Bouras E, Papandreou C, Tzoulaki I, Tsilidis Ket al., 2021, Endogenous sex steroid hormones and colorectal cancer risk: a systematic review and meta-analysis, Discover Oncology, Vol: 12, Pages: 1-1, ISSN: 2730-6011

Preclinical data suggest that endogenous sex steroid hormones may be implicated in colorectal cancer (CRC) development, however, findings from epidemiological studies are conflicting. The aim of this systematic review and meta-analysis was to investigate the associations between endogenous concentrations of sex hormones and CRC risk. PubMed and Scopus were searched until June 2020 for prospective studies evaluating the association between pre-diagnostic plasma/serum concentrations of estradiol, testosterone and sex-hormone binding globulin (SHBG) and CRC risk. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using the inverse-variance weighted random-effects model based on the DerSimonian-Laird estimator. Eight studies were included in the meta-analysis after evaluating 3,859 non-duplicate records. Four of the eight studies had a nested case–control design, one study was a case-cohort and the rest three studies were cohort studies, and they included on average 295 cases (range:48–732) and 2,105 controls. No associations were found for endogenous sex steroid hormones in men or post-menopausal women with CRC risk, with evidence for substantial heterogeneity observed among women. Findings from this meta-analysis do not support presence of associations between pre-diagnostic concentrations of testosterone, estradiol and SHBG with incident CRC risk in men and post-menopausal women.

Journal article

Sofianopoulou E, Kaptoge S, Afzal S, Jiang T, Gill D, Willeit J, Tsilidis K, Heath A, Danesh J, Butterworth A, Burgess Set al., 2021, Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses, The Lancet Diabetes & Endocrinology, Vol: 9, Pages: 837-846, ISSN: 2213-8587

BackgroundRandomised trials of vitamin D supplementation for cardiovascular disease and all-cause mortality have generally reported null findings. However, generalisability of results to individuals with low vitamin D status is unclear. We aimed to characterise dose-response relationships between 25-hydroxyvitamin D (25[OH]D) concentrations and risk of coronary heart disease, stroke, and all-cause mortality in observational and Mendelian randomisation frameworks.MethodsObservational analyses were undertaken using data from 33 prospective studies comprising 500 962 individuals with no known history of coronary heart disease or stroke at baseline. Mendelian randomisation analyses were performed in four population-based cohort studies (UK Biobank, EPIC-CVD, and two Copenhagen population-based studies) comprising 386 406 middle-aged individuals of European ancestries, including 33 546 people who developed coronary heart disease, 18 166 people who had a stroke, and 27 885 people who died. Primary outcomes were coronary heart disease, defined as fatal ischaemic heart disease (International Classification of Diseases 10th revision code I20-I25) or non-fatal myocardial infarction (I21-I23); stroke, defined as any cerebrovascular disease (I60-I69); and all-cause mortality.FindingsObservational analyses suggested inverse associations between incident coronary heart disease, stroke, and all-cause mortality outcomes with 25(OH)D concentration at low 25(OH)D concentrations. In population-wide genetic analyses, there were no associations of genetically-predicted 25(OH)D with coronary heart disease, stroke, or all-cause mortality. However, for the participants with vitamin D deficiency (25[OH]D concentration <25 nmol/L), genetic analyses provided strong evidence for an inverse association with all-cause mortality (odds ratio [OR] per 10 nmol/L increase in genetically-predicted 25[OH]D concentration 0·69 [95% CI 0·59–0&middo

Journal article

Mori N, Keski-Rahkonen P, Gicquiau A, Rinaldi S, Dimou N, Harlid S, Harbs J, Van Guelpen B, Aune D, Cross AJ, Tsilidis KK, Severi G, Kvaskoff M, Fournier A, Kaaks R, Fortner RT, Schulze MB, Jakszyn P, Sánchez M-J, Colorado-Yohar SM, Ardanaz E, Travis R, Watts EL, Masala G, Krogh V, Tumino R, Sacerdote C, Panico S, de-Mesquita BB, Gram IT, Waaseth M, Gunter MJ, Murphy Net al., 2021, Endogenous circulating sex hormone concentrations and colon cancer risk in postmenopausal women: a prospective study and meta-analysis, JNCI Cancer Spectrum, Vol: 5, Pages: 1-10, ISSN: 2515-5091

BackgroundObservational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk. However, epidemiological studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results.MethodsWe investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone binding globulin (SHBG) with colon cancer risk in a nested case–control study of 1,028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were non-current users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided.ResultsIn the multivariable model, a non-statistically significant positive relationship was found between circulating estrone and colon cancer risk (OR per log2-1 unit increment = 1.17, 95%CI = 1.00–1.38; ORquartile4-quartile1 = 1.33, 95%CI = 0.89–1.97, Ptrend = 0.20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol, and estrone concentrations with colorectal, colon, and rectal cancer risk.ConclusionOur observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex horm

Journal article

Charvat H, Freisling H, Noh H, Gaudet MM, Gunter MJ, Cross AJ, Tsilidis KK, Tjønneland A, Katzke V, Bergmann M, Agnoli C, Rylander C, Skeie G, Jakszyn P, Rosendahl AH, Sund M, Severi G, Tsugane S, Sawada N, Brenner H, Adami H-O, Weiderpass E, Soerjomataram I, Arnold Met al., 2021, Excess Body Fatness during Early to Mid-Adulthood and Survival from Colorectal and Breast Cancer: A Pooled Analysis of Five International Cohort Studies., Cancer Epidemiol Biomarkers Prev

BACKGROUND: Here, we explore the association between excess weight during early to mid-adulthood and survival in patients diagnosed with breast and colorectal cancer, using a pooled analysis of five cohort studies and study participants from 11 countries. METHODS: Participant-level body mass index (BMI) trajectories were estimated by fitting a growth curve model using over 2 million repeated BMI measurements from close to 600,000 cohort participants. Cumulative measures of excess weight were derived. Data from over 23,000 patients with breast and colorectal cancer were subsequently analyzed using time-to-event models for death with the date of diagnosis as start of follow-up. Study-specific results were combined through a random effect meta-analysis. RESULTS: We found a significant dose-response relationship (P trend = 0.013) between the average BMI during early and mid-adulthood and death from breast cancer, with a pooled HR of 1.31 (1.07-1.60) and the time to death shortened by 16% for average BMI above 25 kg/m2 compared with average BMI less than or equal to 22.5 kg/m2, respectively. Similar results were found for categories of cumulative time spent with excess weight. There was no association between excess body fatness during early to mid-adulthood and death in patients with colorectal cancer. CONCLUSIONS: Excess body fatness during early to mid-adulthood is associated not only with an increased risk of developing cancer, but also with a lower survival in patients with breast cancer. IMPACT: Our results emphasize the importance of public health policies aimed at reducing overweight during adulthood and inform future studies on the relationship between excess weight and cancer outcomes.

Journal article

Laine J, Huybrechts I, Gunter M, Ferrari P, Weiderpass E, Tsilidis K, Dagfinn A, Schulze M, Bergmann M, Temme E, Boer JMA, Agnoli C, Ericson U, Stubbendorff A, Ibsen DB, Dahm CC, Deschasaux M, Touvier M, Kesse-Guyot E, Sánchez M-J, Barranco MR, Tong TYN, Papier K, Knuppel A, Boutron-Ruault M-C, Mancini F, Severi G, Srour B, Kühn T, Masala G, Agudo A, Skeie G, Rylander C, Sandanger TM, Riboli E, Vineis Pet al., 2021, Co-benefits from sustainable dietary shifts for population and environmental health: an assessment from a large European cohort study, The Lancet Planetary Health, Vol: 5, Pages: e786-e796, ISSN: 2542-5196

Background: Unhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas (GHG) emissions, substantial land use, (LU) and adverse health outcomes such as cancer and mortality. Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), a multi-centre prospective cohort study (n=443,991), we estimated associations between dietary contributions to GHG emissions and LU and all-cause and cause-specific mortality and incident cancers using Cox proportional-hazard regression models. Co-benefits, encompassing the potential effects of alternative diets on all-cause mortality and cancer and potential reduction in GHG emissions and LU, were estimated using counterfactual attributable fraction (AF) intervention models, simulating potential effects from dietary shifts based on the EAT-Lancet reference diet. Findings: There was an association between levels of dietary-based GHG emissions and LU and all-cause mortality, with a Hazard Ratio and 95% Confidence Interval (CI) of 1.13 (1.10, 1.16) and 1.18 (95% CI: 1.15, 1.21), respectively, comparing the fourth quartile to the first (HRQ4 vs Q1). Similar associations were observed for cause-specific mortality. There were also associations between overall cancer rates and GHG emissions (HRQ4 vs Q1: 1.11, 95% CI: 1.09, 1.14) and LU (HRQ4 vs Q1: 1.13, 95% CI: 1.10, 1.15); however, estimates differed by cancer type. Through counterfactual AF modelling of shifts in diets, we find that between 19 to 63% of deaths and 10 to 39% of cancers could be prevented, over a 20-year risk period, from adhering to different scores of the EAT-Lancet reference diet. Additionally, switching from a lower score of the EAT-Lancet reference diet to a higher score could reduce food-associated GHG and LU levels by 50% and 62%, respectively.Interpretation: Our results support shifts in diets that

Journal article

Christakoudi S, Tsilidis K, Evangelou E, Riboli Eet al., 2021, Association of body-shape phenotypes with imaging measures of body composition in the UK Biobank cohort: relevance to colon cancer risk, BMC Cancer, Vol: 21, Pages: 1-15, ISSN: 1471-2407

BackgroundBody mass index (BMI), waist and hip circumference are strongly correlated and do not reflect body composition. A Body Shape Index (ABSI) and Hip Index (HI) define waist and hip size among individuals with the same weight and height and would thus reflect body density. We examined differences in body composition between body-shape phenotypes defined with ABSI and HI and used this information to propose explanations for associations between body-shape phenotypes and colon cancer risk.MethodsWe used data from the UK Biobank Resource for 15,520 men, 16,548 women with dual-emission X-ray absorptiometry (DXA) measurements; 3997 men, 4402 women with magnetic resonance imaging (MRI) measurements; 200,289 men, 230,326 women followed-up for colon cancer. We defined body-shape phenotypes as: large-ABSI-small-HI (“apple”), small-ABSI-large-HI (“pear”), small-ABSI-small-HI (“slim”), large-ABSI-large-HI (“wide”). We evaluated differences in body composition in linear models and associations with colon cancer risk in Cox proportional hazards models adjusted for confounders and explored heterogeneity by BMI.ResultsAmong individuals with the same height and weight, visceral adipose tissue (VAT) was lowest for “pear” and highest for “apple”, while abdominal subcutaneous adipose tissue (ASAT) was lowest for “slim” and highest for “wide” phenotype. In the gynoid region, differences between “apple” and “pear” phenotypes were accounted for mainly by fat mass in women but by lean mass in men. In men, lean mass was inversely associated with waist size, while the pattern of gynoid fat resembled ASAT in women. Lean and fat mass were higher for higher BMI, but not hand grip strength. Compared to normal weight “pear”, the risk of colon cancer in men (1029 cases) was higher for “apple” phenotype for normal weight (hazard ratio HR =&thi

Journal article

Al-Jafar R, Zografou Themeli M, Zaman S, Akbar S, Lhoste V, Khamliche A, Elliott P, Tsilidis KK, Dehghan Aet al., 2021, Effect of religious fasting in Ramadan on blood pressure: results from LORANS (London Ramadan Study) and a meta-analysis., Journal of the American Heart Association, Vol: 10, Pages: 1-36, ISSN: 2047-9980

Background Ramadan fasting is practiced by hundreds of millions every year. This ritual practice changes diet and lifestyle dramatically; thus, the effect of Ramadan fasting on blood pressure must be determined. Methods and Results LORANS (London Ramadan Study) is an observational study, systematic review, and meta-analysis. In LORANS, we measured systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 85 participants before and right after Ramadan. In the systematic review, studies were retrieved from PubMed, Embase, and Scopus from inception to March 3, 2020. We meta-analyzed the effect from these studies and unpublished data from LORANS. We included observational studies that measured SBP and/or DBP before Ramadan and during the last 2 weeks of Ramadan or the first 2 weeks of the month after. Data appraisal and extraction were conducted by at least 2 reviewers in parallel. We pooled SBP and DBP using a random-effects model. The systematic review is registered with PROSPERO (International Prospective Register of Systematic Reviews; CRD42019159477). In LORANS, 85 participants were recruited; mean age was 45.6±15.9 years, and 52.9% (n=45) of participants were men. SBP and DBP after Ramadan fasting were lower by 7.29 mm Hg (-4.74 to -9.84) and 3.42 mm Hg (-1.73 to -5.09), even after adjustment for potential confounders. We identified 2778 studies of which 33 with 3213 participants were included. SBP and DBP after/before Ramadan were lower by 3.19 mm Hg (-4.43 to -1.96, I2=48%) and 2.26 mm Hg (-3.19 to -1.34, I2=66%), respectively. In subgroup analyses, lower blood pressures were observed in the groups who are healthy or have hypertension or diabetes but not in patients with chronic kidney disease. Conclusions Our study suggests beneficial effects of Ramadan fasting on blood pressure independent of changes in weight, total body water, and fat mass and supports recommendations for some government

Journal article

Hanley-Cook GT, Huybrechts I, Biessy C, Remans R, Kennedy G, Deschasaux-Tanguy M, Murray KA, Touvier M, Skeie G, Kesse-Guyot E, Argaw A, Casagrande C, Nicolas G, Vineis P, Millett CJ, Weiderpass E, Ferrari P, Dahm CC, Bueno-de-Mesquita HB, Sandanger TM, Ibsen DB, Freisling H, Ramne S, Jannasch F, van der Schouw YT, Schulze MB, Tsilidis KK, Tjonneland A, Ardanaz E, Boden S, Cirera L, Gargano G, Halkjaer J, Jakszyn P, Johansson I, Katzke V, Masala G, Panico S, Rodriguez-Barranco M, Sacerdote C, Srour B, Tumino R, Riboli E, Gunter MJ, Jones AD, Lachat Cet al., 2021, Food biodiversity and total and cause-specific mortality in 9 European countries: An analysis of a prospective cohort study, PLOS MEDICINE, Vol: 18, ISSN: 1549-1277

Journal article

Katsoulis M, Lai AG, Diaz-Ordaz K, Gomes M, Pasea L, Banerjee A, Denaxas S, Tsilidis K, Lagiou P, Misirli G, Bhaskaran K, Wannamethee G, Dobson R, Batterham RL, Kipourou D-K, Lumbers RT, Wen L, Wareham N, Langenberg C, Hemingway Het al., 2021, Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records, The Lancet Diabetes and Endocrinology, Vol: 9, Pages: 681-694, ISSN: 2213-8595

BACKGROUND: Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR). METHODS: In this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions. FINDINGS: We included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4·22 [95% CI 3·86-4·62]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a hig

Journal article

Bassukas ID, Tsilidis KK, Spyridonos P, 2021, Advanced keratinocyte skin cancer is a tumor with considerable disease burden and aggressiveness, Archives of Dermatological Research, Vol: 313, Pages: 707-709, ISSN: 0340-3696

In a 2013 study published in this Journal, Dacosta Byfield et al. used MediCare data to extract reliable estimations of the incidence (I = 6.16) and prevalence (P = 10.31) rates of advanced keratinocyte skin cancer (aKSC) per 100,000 US population. These data unmask a considerable disease burden of aKSC (tumor stages ≥ 3) compared to the corresponding projected SEER predictions in 2019 of all invasive cases (tumor stages ≥ 1). According to its incidence, aKSC ranks 19th out of 29 major SEER registered neoplasms and has an average disease duration of 1.67 years, which is the second shortest disease duration next only to pancreatic carcinoma. Furthermore, in support of the high disease aggressiveness of aKSC and using a calibration approach, we calculated a mortality estimate of 4.64 per 100,000 and a 5-year survival rate of 21.8% for this tumor, which corresponds to positions of 13th and 5th out of 29 cancers among the SEER tracked malignancies, respectively. Taken together, these data indicate a considerable disease burden and biologic aggressiveness of aKSC.

Journal article

Koutsonida M, Kanellopoulou A, Markozannes G, Gousia S, Doumas MT, Sigounas DE, Tzovaras VT, Vakalis K, Tzoulaki I, Evangelou E, Rizos EC, Ntzani E, Aretouli E, Tsilidis KKet al., 2021, Adherence to Mediterranean diet and cognitive abilities in the Greek cohort of Epirus Health Study, Nutrients, Vol: 13, ISSN: 2072-6643

The Mediterranean diet is commonly proposed as a major modifiable protective factor that may delay cognitive impairment in the elderly. The aim of the study was to investigate the cross-sectional association of adherence to the Mediterranean diet with cognitive abilities in a younger Greek population. A total of 1201 healthy adults aged 21–77 years (mean: 47.8) from the Epirus Health Study cohort were included in the analysis. Adherence to the Mediterranean diet was measured using the 14-point Mediterranean Diet Adherence Screener (MEDAS) and cognition was measured using the Trail Making Test, the Verbal Fluency test and the Logical Memory test. Statistical analysis was performed using multiple linear regression models adjusted for age, sex, education, body mass index, smoking status, alcohol consumption and physical activity. Overall, no association was found between the MEDAS score and cognitive tests, which could be explained by the young mean age and high level of education of the participants. Future studies should target young and middle-aged individuals to gain further understanding of the association between Mediterranean diet and cognition in this age group.

Journal article

Katsoulis M, Stavola BD, Diaz-Ordaz K, Gomes M, Lai A, Lagiou P, Wannamethee G, Tsilidis K, Lumbers RT, Denaxas S, Banerjee A, Parisinos CA, Batterham R, Patel R, Langenberg C, Hemingway Het al., 2021, Weight change and the onset of cardiovascular diseases: emulating trials using electronic health records., Epidemiology, Vol: 32, Pages: 744-755, ISSN: 1044-3983

BACKGROUND: Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD. METHODS: We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45-69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group. RESULTS: Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance = 1.5% (0.3% to 3.0%)] and gain [RD = 1.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD = 0.7% (-0.2% to 1.7%)] and the weight gain group [RD = 0.7% (-0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD = -1.4% (-2.4% to -0.6%)] but not of stroke. When we assumed that chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals. CONCLUSION: Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at, http://links.lww.com/EDE/B838.

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Tsilidis K, 2021, Prevalence and determinants of sex-specific dietary supplement use in a Greek cohort, Nutrients, Vol: 13, Pages: 1-15, ISSN: 2072-6643

We describe the profile of dietary supplement use and its correlates in the Epirus Health Study cohort, which consists of 1,237 adults (60.5% women) residing in urban north-west Greece. The association between dietary supplement use and demographic characteristics, lifestyle behaviours, personal medical history and clinical measurements was assessed using logistic regression models, separately for women and men. The overall prevalence of dietary supplement use was 31.4%, and it was higher in women (37.3%) compared to men (22.4%; p-value=4.2-08). Based on multivariable logistic regression models, dietary supplement use in women was associated with age (positively until middle-age and slightly negatively afterwards), the presence of a chronic health condition (OR=1.71; 95% CI, 1.18-2.46), lost/removed teeth (OR=0.52; 95% CI, 0.35-0.78) and diastolic blood pressure (OR per 5 mmHg increase=0.84; 95% CI, 0.73-0.96); body mass index and worse general health status were borderline inversely associated. In men, dietary supplement use was positively associated with being employed (OR=2.53; 95% CI, 1.21-5.29). A considerable proportion of our sample used dietary supplements, and the factors associated with it differed between women and men.

Journal article

Christakoudi S, Tsilidis K, Evangelou E, Riboli Eet al., 2021, A Body Shape Index (ABSI), hip index and risk of cancer in the UK Biobank cohort, Cancer Medicine, Vol: 10, Pages: 5614-5628, ISSN: 2045-7634

Abdominal size is associated positively with the risk of some cancers but the influence of body mass index (BMI) and gluteofemoral size is unclear because waist and hip circumference are strongly correlated with BMI. We examined associations of 33 cancers with A Body Shape Index (ABSI) and hip index (HI), which are independent of BMI by design, and compared these with waist and hip circumference, using multivariable Cox proportional hazards models in UK Biobank. During a mean follow up of seven years, 14,682 incident cancers were ascertained in 200,289 men and 12,965 cancers in 230,326 women. In men, ABSI was associated positively with cancers of the head and neck (hazard ratio HR=1.14; 95% confidence interval 1.03-1.26 per one standard deviation increment), oesophagus (adenocarcinoma, HR=1.27; 1.12-1.44), gastric cardia (HR=1.31; 1.07-1.61), colon (HR=1.18; 1.10-1.26), rectum (HR=1.13; 1.04-1.22), lung (adenocarcinoma, HR=1.16; 1.03-1.30; squamous-cell carcinoma (SCC), HR=1.33; 1.17-1.52), and bladder (HR=1.15; 1.04-1.27), while HI was associated inversely with cancers of the oesophagus (adenocarcinoma, HR=0.89; 0.79-1.00), gastric cardia (HR=0.79; 0.65-0.96), colon (HR=0.92; 0.86-0.98), liver (HR=0.86; 0.75-0.98), and multiple myeloma (HR=0.86; 0.75-1.00). In women, ABSI was associated positively with cancers of the head and neck (HR=1.27; 1.10-1.48), oesophagus (SCC, HR=1.37; 1.07-1.76), colon (HR=1.08; 1.01-1.16), lung (adenocarcinoma, HR=1.17; 1.06-1.29; SCC, HR=1.40; 1.20-1.63; small-cell, HR=1.39; 1.14-1.69), kidney (clear-cell, HR=1.25; 1.03-1.50), and post-menopausal endometrium (HR=1.11; 1.02-1.20), while HI was associated inversely with skin SCC (HR=0.91; 0.83-0.99), post-menopausal kidney cancer (HR=0.77; 0.67-0.88) and post-menopausal melanoma (HR=0.90; 0.83-0.98). Unusually, ABSI was associated inversely with melanoma in men (HR=0.89; 0.82-0.96) and pre-menopausal women (HR=0.77; 0.65-0.91). Waist and hip circumference reflected associations with BMI

Journal article

Dossus L, Kouloura E, Biessy C, Viallon V, Siskos AP, Dimou N, Rinaldi S, Merritt MA, Allen N, Fortner R, Kaaks R, Weiderpass E, Gram IT, Rothwell JA, Lécuyer L, Severi G, Schulze MB, Nøst TH, Crous-Bou M, Sánchez M-J, Amiano P, Colorado-Yohar SM, Gurrea AB, Schmidt JA, Palli D, Agnoli C, Tumino R, Sacerdote C, Mattiello A, Vermeulen R, Heath AK, Christakoudi S, Tsilidis KK, Travis RC, Gunter MJ, Keun HCet al., 2021, Prospective analysis of circulating metabolites and endometrial cancer risk, Gynecologic Oncology, Vol: 162, Pages: 475-481, ISSN: 0090-8258

AbstractBackgroundEndometrial cancer is strongly associated with obesity and dysregulation of metabolic factors such as estrogen and insulin signaling are causal risk factors for this malignancy. To identify additional novel metabolic pathways associated with endometrial cancer we performed metabolomic analyses on pre-diagnostic plasma samples from 853 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC).MethodsA total of 129 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexoses, and sphingolipids) were measured by liquid chromatography-mass spectrometry. Conditional logistic regression estimated the associations of metabolites with endometrial cancer risk. An analysis focusing on clusters of metabolites using the bootstrap lasso method was also employed.ResultsAfter adjustment for body mass index, sphingomyelin [SM] C18:0 was positively (OR1SD: 1.18, 95% CI: 1.05–1.33), and glycine, serine, and free carnitine (C0) were inversely (OR1SD: 0.89, 95% CI: 0.80–0.99; OR1SD: 0.89, 95% CI: 0.79–1.00 and OR1SD: 0.91, 95% CI: 0.81–1.00, respectively) associated with endometrial cancer risk. Serine, C0 and two sphingomyelins were selected by the lasso method in >90% of the bootstrap samples. The ratio of esterified to free carnitine (OR1SD: 1.14, 95% CI: 1.02–1.28) and that of short chain to free acylcarnitines (OR1SD: 1.12, 95% CI: 1.00–1.25) were positively associated with endometrial cancer risk. Further adjustment for C-peptide or other endometrial cancer risk factors only minimally altered the results.ConclusionThese findings suggest that variation in levels of glycine, serine, SM C18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention.

Journal article

Tsilidis K, 2021, An umbrella review of the evidence associating diet and cancer risk at 11 anatomical sites, Nature Communications, Vol: 12, Pages: 1-10, ISSN: 2041-1723

There is evidence that diet and nutrition are modifiable risk factors for several cancers, but associations may be flawed due to inherent biases. Nutritional epidemiology studies have largely relied on a single assessment of diet using food frequency questionnaires. We conduct an umbrella review of meta-analyses of observational studies to evaluate the strength and validity of the evidence for the association between food/nutrient intake and risk of developing or dying from 11 primary cancers. It is estimated that only few single food/nutrient and cancer associations are supported by strong or highly suggestive meta-analytic evidence, and future similar research is unlikely to change this evidence. Alcohol consumption is positively associated with risk of postmenopausal breast, colorectal, esophageal, head & neck and liver cancer. Consumption of dairy products, milk, calcium and wholegrains are inversely associated with colorectal cancer risk. Coffee consumption is inversely associated with risk of liver cancer and skin basal cell carcinoma.

Journal article

Ried-Larsen M, Rasmussen MG, Blond K, Overvad TF, Overvad K, Steindorf K, Katzke V, Andersen JLM, Petersen KEN, Aune D, Tsilidis KK, Heath AK, Papier K, Panico S, Masala G, Pala V, Weiderpass E, Freisling H, Bergmann MM, Verschuren WMM, Zamora-Ros R, Colorado-Yohar SM, Spijkerman AMW, Schulze MB, Ardanaz EMA, Andersen LB, Wareham N, Brage S, Grøntved Aet al., 2021, Association of cycling with all-cause and cardiovascular disease mortality among persons with diabetes. The European Prospective Investigation into Cancer and Nutrition (EPIC) study, JAMA Internal Medicine, ISSN: 2168-6106

Importance: Premature death from all causes and cardiovascular disease (CVD) causes is higher among persons with diabetes.Objective: To investigate the association between time spent cycling and all-cause and CVD mortality among persons with diabetes, as well as to evaluate the association between change in time spent cycling and risk of all-cause and CVD mortality.Design, Setting, and Participants: This prospective cohort study included 7459 adults with diabetes from the European Prospective Investigation into Cancer and Nutrition study. Questionnaires regarding medical history, sociodemographic, and lifestyle information were administered in 10 Western European countries from 1992 through 2000 (baseline examination) and at a second examination 5 years after baseline. A total of 5423 participants with diabetes completed both examinations. The final updated primary analysis was conducted on November 13, 2020.Exposures: The primary exposure was self-reported time spent cycling per week at the baseline examination. The secondary exposure was change in cycling status from baseline to the second examination.Main Outcomes and Measures The primary and secondary outcomes were all-cause and CVD mortality, respectively, adjusted for other physical activity modalities, diabetes duration, and sociodemographic and lifestyle factors.Results: Of the 7459 adults with diabetes included in the analysis, the mean (SD) age was 55.9 (7.7) years, and 3924 (52.6%) were female. During 110 944 person-years of follow-up, 1673 deaths from all causes were registered. Compared with the reference group of people who reported no cycling at baseline (0 min/wk), the multivariable-adjusted hazard ratios for all-cause mortality were 0.78 (95% CI, 0.61-0.99), 0.76 (95% CI, 0.65-0.88), 0.68 (95% CI, 0.57-0.82), and 0.76 (95% CI, 0.63-0.91) for cycling 1 to 59, 60 to 149, 150 to 299, and 300 or more min/wk, respectively. In an analysis of change in time spent cycling with 57 802 person-years of f

Journal article

Janiaud P, Agarwal A, Tzoulaki I, Theodoratou E, Tsilidis KK, Evangelou E, Ioannidis JPAet al., 2021, Validity of observational evidence on putative risk and protective factors: appraisal of 3744 meta-analyses on 57 topics, BMC Medicine, Vol: 19, ISSN: 1741-7015

BACKGROUND: The validity of observational studies and their meta-analyses is contested. Here, we aimed to appraise thousands of meta-analyses of observational studies using a pre-specified set of quantitative criteria that assess the significance, amount, consistency, and bias of the evidence. We also aimed to compare results from meta-analyses of observational studies against meta-analyses of randomized controlled trials (RCTs) and Mendelian randomization (MR) studies. METHODS: We retrieved from PubMed (last update, November 19, 2020) umbrella reviews including meta-analyses of observational studies assessing putative risk or protective factors, regardless of the nature of the exposure and health outcome. We extracted information on 7 quantitative criteria that reflect the level of statistical support, the amount of data, the consistency across different studies, and hints pointing to potential bias. These criteria were level of statistical significance (pre-categorized according to 10-6, 0.001, and 0.05 p-value thresholds), sample size, statistical significance for the largest study, 95% prediction intervals, between-study heterogeneity, and the results of tests for small study effects and for excess significance. RESULTS: 3744 associations (in 57 umbrella reviews) assessed by a median number of 7 (interquartile range 4 to 11) observational studies were eligible. Most associations were statistically significant at P < 0.05 (61.1%, 2289/3744). Only 2.6% of associations had P < 10-6, ≥1000 cases (or ≥20,000 participants for continuous factors), P < 0.05 in the largest study, 95% prediction interval excluding the null, and no large between-study heterogeneity, small study effects, or excess significance. Across the 57 topics, large heterogeneity was observed in the proportion of associations fulfilling various quantitative criteria. The quantitative criteria were mostly independent from one another. Across 62 associations assessed in both RCTs and in o

Journal article

Diez-Obrero V, Van Duijnhoven F, Kim AE, Baurley J, Campbell PT, Carreras-Torres R, Chang-Claude J, Conti DV, Jenab M, Hsu L, Jordahl KM, Lewinger JP, Lin Y, Newcomb PA, Obon-Santacana M, Bens P, Anita P, Qu C, Ruiz-Narvaez E, Tian Y, Tsilidis K, Casey G, Peters U, Gauderman JW, Moreno Vet al., 2021, Genome-wide gene-calcium interaction in relation to colorectal cancer risk., Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472

Conference paper

Laiou E, Rapti I, Schwarzer R, Fleig L, Cianferotti L, Ngo J, Rizos EC, Wetle TF, Kahlmeier S, Vigilanza A, Tsilidis KK, Trichopoulou A, Serra-Majem L, Brandi ML, Ntzani EEet al., 2021, Review: Nudge interventions to promote healthy diets and physical activity, FOOD POLICY, Vol: 102, ISSN: 0306-9192

Journal article

Dimou N, Kim AE, Flanagan O, Murphy N, Bouras E, Campbell PT, Casey G, Gallinger S, Gruber SB, Hsu L, Jenkins MA, Lin Y, Moreno V, Qu C, Ruiz-Narvaez E, Stern MC, Tian Y, Tsilidis K, Gauderman WJ, Gunter MJ, Peters Uet al., 2021, Probing the diabetes - colorectal cancer link using gene - environment interaction analyses., Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472

Conference paper

Papadimitriou N, Hidaka A, Kim A, Dimou N, Murphy N, Berndt SI, Conti D, Campbell PT, Casey G, Figueiredo JC, Tsilidis KK, Gruber SB, Harlid S, Lin Y, Moreno V, Sakoda LC, Obrero VD, Hsu L, Gauderman WJ, Gunter M, Peters Uet al., 2021, Consumption of fruits, vegetables and fiber and risk of colorectal cancer: A gene environment interaction analysis., Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472

Conference paper

Gill D, Zuber V, Dawson J, Pearson-Stuttard J, Carter AR, Sanderson E, Karhunen V, Levin MG, Wootton RE, Klarin D, Tsao PS, Tsilidis KK, Damrauer SM, Burgess S, Elliott Pet al., 2021, Risk factors mediating the effect of body mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis, International Journal of Obesity, Vol: 45, Pages: 1428-1438, ISSN: 0307-0565

BackgroundHigher body mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits, and smoking is not fully understood.MethodsUsing consortia and UK Biobank genetic association summary data from 140,595 to 898,130 participants predominantly of European ancestry, Mendelian randomization mediation analysis was performed to investigate the degree to which systolic blood pressure (SBP), diabetes, lipid traits, and smoking mediated an effect of BMI and WHR on the risk of coronary artery disease (CAD), peripheral artery disease (PAD) and stroke.ResultsThe odds ratio of CAD per 1-standard deviation increase in genetically predicted BMI was 1.49 (95% CI 1.39 to 1.60). This attenuated to 1.34 (95% CI 1.24 to 1.45) after adjusting for genetically predicted SBP (proportion mediated 27%, 95% CI 3% to 50%), to 1.27 (95% CI 1.17 to 1.37) after adjusting for genetically predicted diabetes (41% mediated, 95% CI 18% to 63%), to 1.47 (95% CI 1.36 to 1.59) after adjusting for genetically predicted lipids (3% mediated, 95% −23% to 29%), and to 1.46 (95% CI 1.34 to 1.58) after adjusting for genetically predicted smoking (6% mediated, 95% CI −20% to 32%). Adjusting for all the mediators together, the estimate attenuated to 1.14 (95% CI 1.04 to 1.26; 66% mediated, 95% CI 42% to 91%). A similar pattern was observed when considering genetically predicted WHR as the exposure, and PAD or stroke as the outcome.ConclusionsMeasures to reduce obesity will lower the risk of cardiovascular disease primarily by impacting downstream metabolic risk factors, particularly diabetes and hypertension. Reduction of obesity prevalence alongside control and management of its mediators is likely to be most effective for minimizing the burden of obesity.

Journal article

Lopez DS, Polychronopoulou E, Tsilidis KK, Khera M, Su LJ, Fowke JH, Peek MK, Kuo Y-F, Markides K, Canfield Set al., 2021, Independent and Joint Effects of Testosterone Replacement Therapy and Statins use on the Risk o Prostate Cancer Among White, Black, and Hispanic Men, CANCER PREVENTION RESEARCH, Vol: 14, Pages: 719-728, ISSN: 1940-6207

Journal article

Agudo A, Cayssials V, Bonet C, Tjønneland A, Overvad K, Boutron-Ruault M-C, Affret A, Fagherazzi G, Katzke V, Schubel R, Trichopoulou A, Karakatsani A, La Vecchia C, Palli D, Grioni S, Tumino R, Ricceri F, Panico S, Bueno-de-Mesquita B, Peeters PH, Weiderpass E, Skeie G, Nøst TH, Lasheras C, Rodríguez-Barranco M, Amiano P, Chirlaque M-D, Ardanaz E, Ohlsson B, Dias JA, Nilsson LM, Myte R, Khaw K-T, Perez-Cornago A, Gunter M, Huybrechts I, Cross AJ, Tsilidis K, Riboli E, Jakszyn Pet al., 2021, Inflammatory potential of the diet & risk of gastric cancer in the European Investigation into Cancer & Nutrition, American Journal of Clinical Nutrition, Vol: 36, Pages: 953-964, ISSN: 1938-3207

The role of chronic inflammation on breast cancer (BC) risk remains unclear beyond as an underlying mechanism of obesity and physical activity. We aimed to evaluate the association between the inflammatory potential of the diet and risk of BC overall, according to menopausal status and tumour subtypes. Within the European Prospective Investigation into Cancer and Nutrition cohort, 318,686 women were followed for 14 years, among whom 13,246 incident BC cases were identified. The inflammatory potential of the diet was characterized by an inflammatory score of the diet (ISD). Multivariable Cox regression models were used to assess the potential effect of the ISD on BC risk by means of hazard ratios (HR) and 95% confidence intervals (CI). ISD was positively associated with BC risk. Each increase of one standard deviation (1-Sd) of the score increased by 4% the risk of BC (HR = 1.04; 95% CI 1.01–1.07). Women in the highest quintile of the ISD (indicating a most pro-inflammatory diet) had a 12% increase in risk compared with those in the lowest quintile (HR = 1.12; 95% CI 1.04–1.21) with a significant trend. The association was strongest among premenopausal women, with an 8% increased risk for 1-Sd increase in the score (HR = 1.08; 95% CI 1.01–1.14). The pattern of the association was quite homogeneous by BC subtypes based on hormone receptor status. There were no significant interactions between ISD and body mass index, physical activity, or alcohol consumption. Women consuming more pro-inflammatory diets as measured by ISD are at increased risk for BC, especially premenopausal women.

Journal article

Kanellopoulou A, Koskeridis F, Markozannes G, Bouras E, Soutziou C, Chaliasos K, Doumas MT, Sigounas DE, Tzovaras VT, Panos A, Stergiou Y, Mellou K, Papamichail D, Aretouli E, Chatzidimitriou D, Chatzopoulou F, Bairaktari E, Tzoulaki I, Evangelou E, Rizos EC, Ntzani E, Vakalis K, Tsilidis Ket al., 2021, Awareness, knowledge and trust in the Greek authorities towards COVID-19 pandemic: results from the Epirus Health Study cohort, BMC Public Health, Vol: 21, ISSN: 1471-2458

Background: To assess the level of knowledge and trust in the policy decisions taken regarding the coronavirus disease (COVID-19) pandemic among Epirus Health Study (EHS) participants.Methods: The EHS is an ongoing and deeply-phenotyped prospective cohort study that has recruited 667 participants in northwest Greece until August 31st, 2020. Level of knowledge on coronavirus (SARS-CoV-2) transmission and COVID-19 severity was labeled as poor, moderate or good. Variables assessing knowledge and beliefs towards the pandemic were summarized overall and by sex, age group (25-39, 40-49, 50-59, ≥60 years) and period of report (before the lifting of lockdown measures in Greece: March 30th to May 3rd, and two post-lockdown time periods: May 4th to June 31st, July 1st to August 31st). A hypothesis generating exposure-wide association analysis was conducted to evaluate the associations between 153 agnostically-selected explanatory variables and participants’ knowledge. Correction for multiple comparisons was applied using a false discovery rate (FDR) threshold of 5%.Results: A total of 563 participants (49 years mean age; 60% women) had available information on the standard EHS questionnaire, the clinical and biochemical measurements, and the COVID-19-related questionnaire. Percentages of poor, moderate and good knowledge status regarding COVID-19 were 4.5%, 10.0% and 85.6%, respectively. The majority of participants showed absolute or moderate trust in the Greek health authorities for the management of the epidemic (90.1%), as well as in the Greek Government (84.7%) and the official national sources of information (87.4%). Trust in the authorities was weaker in younger participants and those who joined the study after the lifting of lockdown measures (p-value0.001). None of the factors examined was associated with participants’ level of knowledge after correction for multiple testing.Conclusions: High level of knowledge about the COVID-19 pandemic and t

Journal article

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