Publications
364 results found
Merritt MA, Tzoulaki I, Tworoger SS, et al., 2015, Investigation of Dietary Factors and Endometrial Cancer Risk Using a Nutrient-wide Association Study Approach in the EPIC and Nurses' Health Study (NHS) and NHSII, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 24, Pages: 466-471, ISSN: 1055-9965
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- Citations: 35
Papatheodorou SI, Tsilidis KK, Evangelou E, et al., 2015, Application of credibility ceilings probes the robustness of meta-analyses of biomarkers and cancer risk, JOURNAL OF CLINICAL EPIDEMIOLOGY, Vol: 68, Pages: 163-174, ISSN: 0895-4356
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- Citations: 25
Tsilidis KK, Allen NE, Appleby PN, et al., 2015, Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition, INTERNATIONAL JOURNAL OF CANCER, Vol: 136, Pages: 372-381, ISSN: 0020-7136
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- Citations: 69
Tsilidis KK, Kasimis JC, Lopez DS, et al., 2015, Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies, BMJ: British Medical Journal, Vol: 350, ISSN: 0959-535X
Objectives To summarise the evidence and evaluate the validity of the associations between type 2 diabetes and the risk of developing or dying from cancer.Design An umbrella review of the evidence across meta-analyses of observational studies of type 2 diabetes with risk of developing or dying from any cancer.Data sources PubMed, Embase, Cochrane database of systematic reviews, and manual screening of references.Eligibility criteria Meta-analyses or systematic reviews of observational studies in humans that examined the association between type 2 diabetes and risk of developing or dying from cancer.Results Eligible meta-analyses assessed associations between type 2 diabetes and risk of developing cancer in 20 sites and mortality for seven cancer sites. The summary random effects estimates were significant at P=0.05 in 20 meta-analyses (74%); and all reported increased risks of developing cancer for participants with versus without diabetes. Of the 27 meta-analyses, eventually only seven (26%) compiled evidence on more than 1000 cases, had significant summary associations at P≤0.001 for both random and fixed effects calculations, and had neither evidence of small study effects nor evidence for excess significance. Of those, only six (22%) did not have substantial heterogeneity (I2>75%), pertaining to associations between type 2 diabetes and risk of developing breast, cholangiocarcinoma (both intrahepatic and extrahepatic), colorectal, endometrial, and gallbladder cancer. The 95% prediction intervals excluded the null value for four of these associations (breast, intrahepatic cholangiocarcinoma, colorectal, and endometrial cancer).Conclusions Though type 2 diabetes has been extensively studied in relation to risk of developing cancer and cancer mortality and strong claims of significance exist for most of the studied associations, only a minority of these associations have robust supporting evidence without hints of bias.
Lopez DS, Advani S, Tsilidis KK, et al., 2014, Racial and Ethnic Differences in the Association of Metabolic Syndrome with Prostate-Specific Antigen Levels in U.S. Men: NHANES 2001-2006, JOURNAL OF MENS HEALTH, Vol: 11, Pages: 163-170, ISSN: 1875-6867
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- Citations: 1
Tsilis AG, Tsilidis KK, Pelidou S-H, et al., 2014, Systematic review of the association between Alzheimer's disease and chronic glaucoma., Clinical Ophthalmology, Vol: 8, Pages: 2095-2104, ISSN: 1177-5467
A potential association between Alzheimer's disease (AD) and chronic glaucoma has been suggested but results of epidemiological studies have been inconsistent. Therefore, we performed a systematic review and critical appraisal of this literature. We searched systematically in PubMed from December 1964 to September 2013 and identified 239 articles potentially relevant for abstract and full-text review. Statistical heterogeneity (variability) across studies was evaluated using the Cochran Q test and the I (2) statistic, and the Newcastle-Ottawa score was used to assess study quality. Ten studies were finally selected. Compared to non-demented participants, patients with AD had a statistically significant decreased risk of glaucoma but the results were very heterogeneous, and thus summary estimates were not reported (I (2), 89%; P heterogeneity, <0.001). The study results ranged from large positive relative risks identified in small and poorly-conducted studies to weak inverse associations or null estimates observed in some cohort and record-linkage studies, but the summary estimates were essentially driven by a large retrospective cohort using medical claims that may be afflicted by underdiagnosis bias. There was also evidence for substantial publication bias (Egger's P≤0.01). The association of AD and glaucoma is heterogeneous and most studies are small and inadequately designed. Large prospective studies with long follow-ups are warranted to clarify this association.
Nimptsch K, Aleksandrova K, Boeing H, et al., 2014, Plasma Fetuin-a concentration, genetic variation in the AHSG gene and risk of colorectal cancer, 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Tsilidis KK, Capothanassi D, Allen N, et al., 2014, Metformin and cancer risk: A cohort study in the UK Clinical Practice Research Datalink analyzed like a randomized trial, 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Han Y, Love S-A, Bush WS, et al., 2014, Pleiotropy analysis identifies a novel prostate cancer variant at 6p21.33: The PAGE, PRACTICAL, and BPC3 Consortia, 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Lopez DS, Peskoe SB, Tsilidis KK, et al., 2014, Association of variants in genes related to the immune response and obesity with BPH in CLUE II, Prostate Cancer and Prostatic Diseases, Vol: 17, Pages: 353-358, ISSN: 1365-7852
Background:Chronic inflammation and obesity may contribute to the genesis or progression of BPH and BPH-associated lower urinary tract symptoms (LUTS). The influence of variants in genes related to these states on BPH has not been studied extensively. Thus, we evaluated the association of 17 single-nucleotide polymorphisms (SNPs) in immune response genes (IL1B, IL6, IL8, IL10, TNF, CRP, TLR4 and RNASEL) and genes involved in obesity, including insulin regulation (LEP, ADIPOQ, PPARG and TCF7L2), with BPH.Methods:BPH cases (N=568) and age-frequency matched controls (N=568) were selected from among adult male CLUE II cohort participants who responded in 2000 to a mailed questionnaire. BPH was defined as BPH surgery, use of BPH medications or symptomatic BPH (American Urological Association Symptom Index Score ⩾15). Controls were men who had not had BPH surgery, did not use BPH medications and whose symptom score was ⩽7. Age-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression.Results:None of the candidate SNPs was statistically significantly associated with BPH. However, we could not rule out possible weak associations for CRP rs1205 (1082C>T), ADIPOQ rs1501299 (276C>A), PPARG rs1801282 (-49C>G) and TCF7L2 rs7903146 (47833T>C). After summing risk alleles, men with ⩾4 had an increased BPH risk compared with those with ⩽1 (OR, 1.78; 95% CI, 1.10–2.89; Ptrend=0.006).Conclusions:SNPs in genes related to immune response and obesity, especially in combination, may be associated with BPH.
Tsilidis KK, Capothanassi D, Allen NE, et al., 2014, Metformin does not affect cancer risk: a cohort study in the UK clinical practice research datalink analyzed like an intention-to-treat trial, Diabetes Care, Vol: 37, Pages: 2522-2532, ISSN: 0149-5992
OBJECTIVE Meta-analyses of epidemiologic studies have suggested that metformin may reduce cancer incidence, but randomized controlled trials did not support this hypothesis.RESEARCH DESIGN AND METHODS A retrospective cohort study, Clinical Practice Research Datalink, was designed to investigate the association between use of metformin compared with other antidiabetes medications and cancer risk by emulating an intention-to-treat analysis as in a trial. A total of 95,820 participants with type 2 diabetes who started taking metformin and other oral antidiabetes medications within 12 months of their diagnosis (initiators) were followed up for first incident cancer diagnosis without regard to any subsequent changes in pharmacotherapy. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% CI.RESULTS A total of 51,484 individuals (54%) were metformin initiators and 18,264 (19%) were sulfonylurea initiators, and 3,805 first incident cancers were diagnosed during a median follow-up time of 5.1 years. Compared with initiators of sulfonylurea, initiators of metformin had a similar incidence of total cancer (HR 0.96; 95% CI 0.89–1.04) and colorectal (HR 0.92; 95% CI 0.76–1.13), prostate (HR 1.02; 95% CI 0.83–1.25), lung (HR 0.85; 95% CI 0.68–1.07), or postmenopausal breast (HR 1.03; 95% CI 0.82–1.31) cancer or any other cancer.CONCLUSIONS In this large study, individuals with diabetes who used metformin had a similar risk of developing cancer compared with those who used sulfonylureas.
Merritt MA, Riboli E, Weiderpass E, et al., 2014, Dietary fat intake and risk of epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition, Cancer Epidemiology, Vol: 38, Pages: 528-537, ISSN: 1877-7821
There are inconsistent and limited data available to assess the relationship between fat intake and risk ofepithelial ovarian cancer (EOC). We examined the consumption of total fat, fat sources and fat subtypes inrelation to risk of EOC and its major histologic subtypes in the European Prospective Investigation intoCancer and Nutrition which includes incident invasive (n = 1095) and borderline (n = 96) EOC. Coxproportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals(CIs). In multivariate models, we observed no association with consumption of total fat, animal or plantfat, saturated fat, cholesterol, monounsaturated fat, or fatty fish and risk of invasive EOC. There was,however, an increased risk of invasive EOC in the highest category of intake (Quartile 4 vs. Quartile 1) ofpolyunsaturated fat (HR = 1.22, 95% CI = 1.02–1.48, Ptrend = 0.02). We did not observe heterogeneity in therisk associations in comparisons of serous and endometrioid histologic subtypes. This study does notsupport an etiological role for total fat intake in relation to EOC risk; however, based on observations of apositive association between intake of polyunsaturated fat and invasive EOC risk in the current andprevious studies, this fat subtype warrants further investigation to determine its potential role in EOCdevelopment.
Schmidt JA, Allen NE, Almquist M, et al., 2014, Insulin-like Growth Factor-I and Risk of Differentiated Thyroid Carcinoma in the European Prospective Investigation into Cancer and Nutrition, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 23, Pages: 976-985, ISSN: 1055-9965
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- Citations: 40
Rinaldi S, Plummer M, Biessy C, et al., 2014, Thyroid-Stimulating Hormone, Thyroglobulin, and Thyroid Hormones and Risk of Differentiated Thyroid Carcinoma: The EPIC Study, JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, Vol: 106, ISSN: 0027-8874
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- Citations: 68
Joshu CE, Tsilidis KK, Peskoe SB, et al., 2014, The association between circulating high-sensitivity C-reactive protein concentration and pathologic measures of colonic inflammation, CANCER CAUSES & CONTROL, Vol: 25, Pages: 409-418, ISSN: 0957-5243
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- Citations: 10
Papatheodorou SI, Rohrmann S, Lopez DS, et al., 2014, Association between endogenous sex steroid hormones and insulin-like growth factor proteins in US men, CANCER CAUSES & CONTROL, Vol: 25, Pages: 353-363, ISSN: 0957-5243
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- Citations: 3
Campa D, Barrdahl M, Tsilidis KK, et al., 2014, A Genome-Wide "Pleiotropy Scan'' Does Not Identify New Susceptibility Loci for Estrogen Receptor Negative Breast Cancer, PLOS ONE, Vol: 9, ISSN: 1932-6203
Approximately 15–30% of all breast cancer tumors are estrogen receptor negative (ER2). Compared with ER-positive (ER+)disease they have an earlier age at onset and worse prognosis. Despite the vast number of risk variants identified fornumerous cancer types, only seven loci have been unambiguously identified for ER-negative breast cancer. With the aim ofidentifying new susceptibility SNPs for this disease we performed a pleiotropic genome-wide association study (GWAS). Weselected 3079 SNPs associated with a human complex trait or disease at genome-wide significance level (P,561028)toperform a secondary analysis of an ER-negative GWAS from the National Cancer Institute’s Breast and Prostate CancerCohort Consortium (BPC3), including 1998 cases and 2305 controls from prospective studies. We then tested the top tenassociations (i.e. with the lowest P-values) using three additional populations with a total sample size of 3509 ER+cases,2543 ER2cases and 7031 healthy controls. None of the 3079 selected variants in the BPC3 ER-GWAS were significant at theadjusted threshold. 186 variants were associated with ER2breast cancer risk at a conventional threshold of P,0.05, with P-values ranging from 0.049 to 2.361024. None of the variants reached statistical significance in the replication phase. Inconclusion, this study did not identify any novel susceptibility loci for ER-breast cancer using a ‘‘pleiotropic approach’’.
Apostolopoulou E, Raftopoulos V, Zarkadas P, et al., 2014, Risk factors and attributable mortality of carbapenem-resistant acinetobacter baumannii infections, Health Science Journal, Vol: 8, Pages: 126-136, ISSN: 1108-7366
Background: The incidence density, the risk factors and the attributable mortality of carbapenem-resistant Acinetobacter baumannii (CR-AB) infections are rarely investigated. Aim: The aim of the present study was to determine the risk factors for CR-AB infection and to investigate whether CR-AB infection significantly increases the 28-day ICU mortality rate. Methods: A matched case-control study was conducted at the Medical/Surgical intensive care unit (ICU) of "SOTIRIA" general hospital in Athens, Greece from January 2009 to March 2010. Out of 156 ICU-admitted patients, 50 case-control pairs were selected. Cases were patients who acquired microbiologically documented CR-AB infection, while control patients without A. baumannii infection and were matched to the cases on APACHE II score, age, and length of ICU stay. Results: The incidence density of CR-AB infections was 16.8 /1000 ICU days. Multivariate conditional logistic regression analysis showed that the previous exposure to more than three different antibiotic classes was the only independent risk factor for the development of CR-AB (OR=34.0, 95% CI=2.22-522, P=0.01). The 28-day ICU mortality rates for cases and controls were 54% and 52%, respectively. Thus, the crude attributable mortality for CR-AB infections was 0.02 (95% CI=-0.18-0.22, P=0.84). Multivariate logistic regression analysis showed that CR-AB infection was not an independent predictor for 28-day ICU mortality rate (OR=1.40, 95% CI=0.46-4.22,P=0.55). Conclusions: Previous exposure to more than three different antibiotic classes was independently and significantly associated with the development of CR-AB. CR-AB infection was not associated with 28-day ICU mortality.
Tsilidis KK, Rohrmann S, McGlynn KA, et al., 2013, Association between endogenous sex steroid hormones and inflammatory biomarkers in US men, ANDROLOGY, Vol: 1, Pages: 919-928, ISSN: 2047-2919
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- Citations: 53
Evangelou E, Kerkhof HJ, Styrkarsdottir U, et al., 2013, A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip, Annals of the Rheumatic Diseases, Vol: 73, Pages: 2130-2136, ISSN: 1468-2060
OBJECTIVES: Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. METHODS: We performed a two-stage meta-analysis on more than 78,000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. RESULTS: We accumulated 11,277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10(-8)) and follow-up studies (p=7.3×10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10(-6), OR=1.27 in male specific analysis). CONCLUSIONS: Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
Tsilidis KK, Panagiotou OA, Sena ES, et al., 2013, Evaluation of Excess Significance Bias in Animal Studies of Neurological Diseases, PLOS Biology, Vol: 11, ISSN: 1545-7885
Animal studies generate valuable hypotheses that lead to the conduct of preventive or therapeutic clinical trials. We assessed whether there is evidence for excess statistical significance in results of animal studies on neurological disorders, suggesting biases. We used data from meta-analyses of interventions deposited in Collaborative Approach to Meta-Analysis and Review of Animal Data in Experimental Studies (CAMARADES). The number of observed studies with statistically significant results (O) was compared with the expected number (E), based on the statistical power of each study under different assumptions for the plausible effect size. We assessed 4,445 datasets synthesized in 160 meta-analyses on Alzheimer disease (n = 2), experimental autoimmune encephalomyelitis (n = 34), focal ischemia (n = 16), intracerebral hemorrhage (n = 61), Parkinson disease (n = 45), and spinal cord injury (n = 2). 112 meta-analyses (70%) found nominally (p≤0.05) statistically significant summary fixed effects. Assuming the effect size in the most precise study to be a plausible effect, 919 out of 4,445 nominally significant results were expected versus 1,719 observed (p<10−9). Excess significance was present across all neurological disorders, in all subgroups defined by methodological characteristics, and also according to alternative plausible effects. Asymmetry tests also showed evidence of small-study effects in 74 (46%) meta-analyses. Significantly effective interventions with more than 500 animals, and no hints of bias were seen in eight (5%) meta-analyses. Overall, there are too many animal studies with statistically significant results in the literature of neurological disorders. This observation suggests strong biases, with selective analysis and outcome reporting biases being plausible explanations, and provides novel evidence on how these biases might influence the whole research domain of neurological animal literature.
Tsilidis KK, Travis RC, Appleby PN, et al., 2013, Insulin-like growth factor pathway genes and blood concentrations, dietary protein and risk of prostate cancer in the NCI Breast and Prostate Cancer Cohort Consortium (BPC3), INTERNATIONAL JOURNAL OF CANCER, Vol: 133, Pages: 495-504, ISSN: 0020-7136
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- Citations: 27
Machiela MJ, Chen C, Liang L, et al., 2013, One thousand genomes imputation in the national cancer institute breast and prostate cancer cohort consortium aggressive prostate cancer genome-wide association study, PROSTATE, Vol: 73, Pages: 677-689, ISSN: 0270-4137
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- Citations: 6
Tsilidis KK, Allen N, Travis R, et al., 2013, Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition., 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Oei L, Reppe S, Ntzani E, et al., 2013, Functional characterization of GWAS loci associated with fracture risk, Annual Meeting of the American-Society-for-Bone-and-Mineral-Research, Publisher: WILEY-BLACKWELL, ISSN: 0884-0431
Oei L, Nordstrom P, Ntzani E, et al., 2013, The genetic basis of cross-phenotype correlation with bone fracture risk: the GEFOS consortium, Annual Meeting of the American-Society-for-Bone-and-Mineral-Research, Publisher: WILEY-BLACKWELL, ISSN: 0884-0431
Aretouli E, Tsilidis KK, Brandt J, 2013, Four-Year Outcome of Mild Cognitive Impairment: The Contribution of Executive Dysfunction, NEUROPSYCHOLOGY, Vol: 27, Pages: 95-106, ISSN: 0894-4105
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- Citations: 35
Tsilidis KK, Papatheodorou SI, Evangelou E, et al., 2012, Evaluation of Excess Statistical Significance in Meta-analyses of 98 Biomarker Associations with Cancer Risk, JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, Vol: 104, Pages: 1867-1878, ISSN: 0027-8874
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- Citations: 58
Rinaldi S, Lise M, Clavel-Chapelon F, et al., 2012, Body size and risk of differentiated thyroid carcinomas: Findings from the EPIC study, INTERNATIONAL JOURNAL OF CANCER, Vol: 131, Pages: E1004-E1014, ISSN: 0020-7136
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- Citations: 98
Braem MGM, Onland-Moret NC, Schouten LJ, et al., 2012, Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition, PLOS ONE, Vol: 7, ISSN: 1932-6203
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- Citations: 14
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