Imperial College London

Christophe Stevens

Faculty of MedicineSchool of Public Health

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Publication Type

16 results found

Tromp TR, Hartgers ML, Hovingh GK, Vallejo-Vaz AJ, Ray KK, Soran H, Freiberger T, Bertolini S, Harada-Shiba M, Blom DJ, Raal FJ, Cuchel Met al., 2022, Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study, The Lancet, Vol: 399, Pages: 719-728, ISSN: 0140-6736

Background:Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally.Methods:The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with, NCT04815005.Findings:Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12·0 years (IQR 5·5–27·0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14·7 mmol/L (IQR 11·6–18·4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3·93 mmol/L, IQR 2·6–5·8) versus non-high-income countries (9·3 mmol/L, 6·7–12·7), with greater use of three or more lipid-lowering therapies (LLT; high-income 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-h

Journal article

Vallejo-Vaz AJ, Stevens CAT, Lyons ARM, Dharmayat KI, Freiberger T, Hovingh GK, Mata P, Raal FJ, Santos RD, Soran H, Watts GF, Abifadel M, Aguilar-Salinas CA, Alhabib KF, Alkhnifsawi M, Almahmeed W, Alnouri F, Alonso R, Al-Rasadi K, Al-Sarraf A, Al-Sayed N, Araujo F, Ashavaid TF, Banach M, Béliard S, Benn M, Binder CJ, Bogsrud MP, Bourbon M, Chlebus K, Corral P, Davletov K, Descamps OS, Durst R, Ezhov M, Gaita D, Genest J, Groselj U, Harada-Shiba M, Holven KB, Kayikcioglu M, Khovidhunkit W, Lalic K, Latkovskis G, Laufs U, Liberopoulos E, Lima-Martinez MM, Lin J, Maher V, Marais AD, März W, Mirrakhimov E, Miserez AR, Mitchenko O, Nawawi H, Nordestgaard BG, Panayiotou AG, Paragh G, Petrulioniene Z, Pojskic B, Postadzhiyan A, Raslova K, Reda A, Reiner Ž, Sadiq F, Sadoh WE, Schunkert H, Shek AB, Stoll M, Stroes E, Su T-C, Subramaniam T, Susekov AV, Tilney M, Tomlinson B, Truong TH, Tselepis AD, Tybjæg-Hansen A, Vázquez Cárdenas A, Viigimaa M, Wang L, Yamashita S, Tokgozoglu L, Catapano AL, Ray KK, Kastelein JJP, Bruckert E, Vohnout B, Schreier L, Pang J, Ebenbichler C, Dieplinger H, Innerhofer R, Winhofer-Stöckl Y, Greber-Platzer S, Krychtiuk K, Speidl W, Toplak H, Widhalm K, Stulnig T, Huber K, Höllerl F, Rega-Kaun G, Kleemann L, Mäser M, Scholl-Bürgi S, Säly C, Mayer FJ, Sablon G, Tarantino E, Nzeyimana C, Pojskic L, Sisic I, Nalbantic AD, Jannes CE, Pereira AC, Krieger JE, Petrov I, Goudev A, Nikolov F, Tisheva S, Yotov Y, Tzvetkov I, Baass A, Bergeron J, Bernard S, Brisson D, Brunham LR, Cermakova L, Couture P, Francis GA, Gaudet D, Hegele RA, Khoury E, Mancini GBJ, McCrindle BW, Paquette M, Ruel I, Cuevas A, Asenjo S, Wang X, Meng K, Song X, Yong Q, Jiang T, Liu Z, Duan Y, Hong J, Ye P, Chen Y, Qi J, Liu Z, Li Y, Zhang C, Peng J, Yang Y, Yu W, Wang Q, Yuan H, Cheng S, Jiang L, Chong M, Jiao J, Wu Y, Wen W, Xu L, Zhang R, Qu Y, He J, Fan X, Wang Z, Chow E, Pećin I, Perica D, Symeonides P, Vrablik M, Ceska R, Soska V, Tichy L, Adamkova V, Franekova J, Cifkova R, Kramet al., 2021, Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC), The Lancet, Vol: 398, Pages: 1713-1725, ISSN: 0140-6736

BackgroundThe European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally.MethodsUsing FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases.FindingsOf the 61 612 individuals in the registry, 42 167 adults (21 999 [53·6%] women) from 56 countries were included in the study. Of these, 31 798 (75·4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84·2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46·2 years (IQR 34·3–58·0); median age at diagnosis of familial hypercholesterolaemia was 44·4 years (32·5–56·5), with 40·2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17·4% (2·1% for stroke and 5·2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81·1%) were receiving statins and 3691 (21·2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol

Journal article


Conference paper


Conference paper

Hu P, Dharmayat KI, Stevens CAT, Sharabiani MTA, Jones RS, Watts GF, Genest J, Ray KK, Vallejo-Vaz AJet al., 2020, Prevalence of familial hypercholesterolemia among the general population and patients with atherosclerotic cardiovascular disease: a systematic review and meta-analysis., Circulation, Vol: 141, Pages: 1742-1759, ISSN: 0009-7322

Background:Contemporary studies suggest that familial hypercholesterolemia (FH) is more frequent than previously reported and increasingly recognized as affecting individuals of all ethnicities and across many regions of the world. Precise estimation of its global prevalence and prevalence across World Health Organization regions is needed to inform policies aiming at early detection and atherosclerotic cardiovascular disease (ASCVD) prevention. The present study aims to provide a comprehensive assessment and more reliable estimation of the prevalence of FH than hitherto possible in the general population (GP) and among patients with ASCVD.Methods:We performed a systematic review and meta-analysis including studies reporting on the prevalence of heterozygous FH in the GP or among those with ASCVD. Studies reporting gene founder effects and focused on homozygous FH were excluded. The search was conducted through Medline, Embase, Cochrane, and Global Health, without time or language restrictions. A random-effects model was applied to estimate the overall pooled prevalence of FH in the general and ASCVD populations separately and by World Health Organization regions.Results:From 3225 articles, 42 studies from the GP and 20 from populations with ASCVD were eligible, reporting on 7 297 363 individuals/24 636 cases of FH and 48 158 patients/2827 cases of FH, respectively. More than 60% of the studies were from Europe. Use of the Dutch Lipid Clinic Network criteria was the commonest diagnostic method. Within the GP, the overall pooled prevalence of FH was 1:311 (95% CI, 1:250–1:397; similar between children [1:364] and adults [1:303], P=0.60; across World Health Organization regions where data were available, P=0.29; and between population-based and electronic health records–based studies, P=0.82). Studies with ≤10 000 participants reported a higher prevalence (1:200–289) compared with larger cohorts (1:365–407; P<0.001). The pooled pre

Journal article

Abar L, Sobiecki JG, Cariolou M, Nanu N, Vieira AR, Stevens C, Aune D, Greenwood DC, Chan DSM, Norat Tet al., 2019, Body size and obesity during adulthood, and risk of lympho-haematopoietic cancers: an update of the WCRF-AICR systematic review of published prospective studies., Ann Oncol, Vol: 30, Pages: 528-541, ISSN: 0923-7534

BACKGROUND: To summarise the evidence on the associations between body mass index (BMI) and BMI in early adulthood, height, waist circumference (WC) and waist-to-hip ratio (WHR), and risk of lympho-haematopoietic cancers. METHOD: We conducted a meta-analysis of prospective studies and identified relevant studies published up to December 2017 by searching PubMed. A random-effects model was used to calculate dose-response summary relative risks (RRs). RESULTS: Our findings showed BMI, and BMI in early adulthood (aged 18-21years) is associated with the risk of Hodgkin's and non-Hodgkin's lymphoma (HL and NHL), diffuse large beta-cell lymphoma (DLBCL), Leukaemia including acute and chronic myeloid lymphoma (AML and CML), and chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). The summary RR per 5kg/m2 increase in BMI were 1.12 [95% confidence interval (CI): 1.05-1.20] for HL, 1.05 (95% CI: 1.03-1.08) for NHL, 1.11 (95% CI: 1.05-1.16) for DLBCL, 1.06 (95% CI: 1.03-1.09) for ML, 1.09 (95% CI: 1.03-1.15) for leukaemia, 1.13 (95% CI: 1.04-1.24) for AML, 1.13 (95% CI: 1.05-1.22) for CML and 1.04 (95% CI: 1.00-1.09) for CLL, and were1.12 (95% CI: 1.05-1.19) for NHL, 1.22 (95% CI: 1.09-1.37) for DLBCL, and 1.19 (95% CI: 1.03-1.38) for FL for BMI in early adulthood analysis. Results on mortality showed a 15%, 16% and 17% increased risk of NHL, MM and leukaemia, respectively. Greater height increased the risk of NHL by 7%, DLBCL by 10%, FL by 9%, MM by 5% and Leukaemia by 7%. WHR was associated with increased risk of DLBCL by 12%. No association was found between higher WC and risk of MM. CONCLUSION: Our results revealed that general adiposity in adulthood and early adulthood, and greater height may increase the risk of almost all types of lympho-haematopoietic cancers and this adds to a growing body of evidence linking body fatness to several types of cancers.

Journal article

Stevens C, 2018, Value of Information in Health Economics Cost-Effectiveness Analysis

Health Economics(HE) models help decision-making bodies determineoptimal medical treatments based on their respective net benefits.This is done during Cost-Effectiveness analyses(CEA). Often, inputparameters of the model are uncertain and their uncertainty canspread to the result of the CEA. In presence of high uncertainty in theCEA result, decision maker may want to conduct a study to gain newinformation about the model parameters, and thus, avoid making baddecisions. Value of Information analyses(VOI) quantifies decreases inuncertainty due to obtaining perfect or future hypothetical samples.Although these analyses are essential for choosing the right treatments,they are currently underutilised by the HE community because of theircomplexity. This dissertation attempts to resolve this complexity bydescribing VOI calculations in the context of HE CEA analyses. Particularemphasis is placed on calculating the value decrease in uncertaintycaused by a new medical study. This is called Expected Valueof Sample Information(EVSI). In addition, we have developed a simpleonline EVSI calculator that deploys the method presented inStrong, M., Oakley, J. E., Brennan, A., and Breeze, P. (2015). Estimatingthe expected value of sample information using the probabilistic sensitivityanalysis sample: A fast, nonparametric regression-based method.Med DecisMaking, 35(5):570–83.We demonstrate that beside being fast and accurate, this method isalso ideal for automation.

Thesis dissertation

Vallejo-Vaz AJ, De Marco M, Stevens CAT, Akram A, Freiberger T, Hovingh GK, Kastelein JJP, Mata P, Raal FJ, Santos RD, Soran H, Watts GF, Abifadel M, Aguilar-Salinas CA, Al-khnifsawi M, AlKindi FA, Alnouri F, Alonso R, Al-Rasadi K, Al-Sarraf A, Ashavaid TF, Binder CJ, Bogsrud MP, Bourbon M, Bruckert E, Chlebus K, Corral P, Descamps O, Durst R, Ezhov M, Fras Z, Genest J, Groselj U, Harada-Shiba M, Kayikcioglu M, Lalic K, Lam CSP, Latkovskis G, Laufs U, Liberopoulos E, Lin J, Maher V, Majano N, Marais AD, März W, Mirrakhimov E, Miserez AR, Mitchenko O, Nawawi HM, Nordestgaard BG, Paragh G, Petrulioniene Z, Pojskic B, Postadzhiyan A, Reda A, Reiner Ž, Sadoh WE, Sahebkar A, Shehab A, Shek AB, Stoll M, Su T, Subramaniam T, Susekov AV, Symeonides P, Tilney M, Tomlinson B, Truong T, Tselepis AD, Tybjærg-Hansen A, Vázquez-Cárdenas A, Viigimaa M, Vohnout B, Widén E, Yamashita S, Banach M, Gaita D, Jiang L, Nilsson L, Santos LE, Schunkert H, Tokgözoğlu L, Car J, Catapano AL, Ray KKet al., 2018, Overview of the current status of familial hypercholesterolaemia care in over 60 countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC), Atherosclerosis, Vol: 277, Pages: 234-255, ISSN: 0021-9150

Background and aimsManagement of familial hypercholesterolaemia (FH) may vary across different settings due to factors related to population characteristics, practice, resources and/or policies. We conducted a survey among the worldwide network of EAS FHSC Lead Investigators to provide an overview of FH status in different countries.MethodsLead Investigators from countries formally involved in the EAS FHSC by mid-May 2018 were invited to provide a brief report on FH status in their countries, including available information, programmes, initiatives, and management.Results63 countries provided reports. Data on FH prevalence are lacking in most countries. Where available, data tend to align with recent estimates, suggesting a higher frequency than that traditionally considered. Low rates of FH detection are reported across all regions. National registries and education programmes to improve FH awareness/knowledge are a recognised priority, but funding is often lacking. In most countries, diagnosis primarily relies on the Dutch Lipid Clinics Network criteria. Although available in many countries, genetic testing is not widely implemented (frequent cost issues). There are only a few national official government programmes for FH. Under-treatment is an issue. FH therapy is not universally reimbursed. PCSK9-inhibitors are available in ∼2/3 countries. Lipoprotein-apheresis is offered in ∼60% countries, although access is limited.ConclusionsFH is a recognised public health concern. Management varies widely across countries, with overall suboptimal identification and under-treatment. Efforts and initiatives to improve FH knowledge and management are underway, including development of national registries, but support, particularly from health authorities, and better funding are greatly needed.

Journal article

Abar L, Vieira AR, Aune D, Sobiecki JG, Vingeliene S, Polemiti E, Stevens C, Greenwood DC, Chan DSM, Schlesinger S, Norat Tet al., 2018, Height and body fatness and colorectal cancer risk: an update of the WCRF-AICR systematic review of published prospective studies, European Journal of Nutrition, Vol: 57, Pages: 1701-1720, ISSN: 0044-264X

PurposeThere is no published dose–response meta-analysis on the association between height and colorectal cancer risk (CRC) by sex and anatomical sub-site. We conducted a meta-analysis of prospective studies on the association between height and CRC risk with subgroup analysis and updated evidence on the association between body fatness and CRC risk.MethodsPubMed and several other databases were searched up to November 2016. A random effects model was used to calculate dose–response summary relative risks (RR’s).Results47 studies were included in the meta-analyses including 50,936 cases among 7,393,510 participants. The findings support the existing evidence regarding a positive association of height, general and abdominal body fatness and CRC risk. The summary RR were 1.04 [95% (CI)1.02–1.05, I² = 91%] per 5 cm increase in height, 1.02 [95% (CI)1.01–1.02, I² = 0%] per 5 kg increase in weight, 1.06 [95% (CI)1.04–1.07, I² = 83%] per 5 kg/m2 increase in BMI, 1.02 [95% (CI)1.02–1.03, I² = 4%] per 10 cm increase in waist circumference, 1.03 [95% (CI)1.01–1.05, I² = 16%] per 0.1 unit increase in waist to hip ratio. The significant association for height and CRC risk was similar in men and women. The significant association for BMI and CRC risk was stronger in men than in women.ConclusionThe positive association between height and risk of CRC suggests that life factors during childhood and early adulthood might play a role in CRC aetiology. Higher general and abdominal body fatness during adulthood are risk factors of CRC and these associations are stronger in men than in women.

Journal article

Vingeliene S, Chan DSM, Vieira AR, Polemiti E, Stevens C, Abar L, Rosenblatt DN, Greenwood DC, Norat Tet al., 2017, An update of the WCRF/AICR systematic literature review and meta-analysis on dietary and anthropometric factors and esophageal cancer risk, Annals of Oncology, Vol: 28, Pages: 2409-2419, ISSN: 0923-7534

BackgroundIn the 2007 World Cancer Research Fund/American Institute for Cancer Research Second Expert Report, the expert panel judged that there was strong evidence that alcoholic drinks and body fatness increased esophageal cancer risk, whereas fruits and vegetables probably decreased its risk. The judgments were mainly based on case–control studies. As part of the Continuous Update Project, we updated the scientific evidence accumulated from cohort studies in this topic.MethodsWe updated the Continuous Update Project database up to 10 January 2017 by searching in PubMed and conducted dose–response meta-analyses to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) using random effects model.ResultsA total of 57 cohort studies were included in 13 meta-analyses. Esophageal adenocarcinoma risk was inversely related to vegetable intake (RR per 100 g/day: 0.89, 95% CI: 0.80–0.99, n = 3) and directly associated with body mass index (RR per 5 kg/m2: 1.47, 95% CI: 1.34–1.61, n = 9). For esophageal squamous cell carcinoma, inverse associations were observed with fruit intake (RR for 100 g/day increment: 0.84, 95% CI: 0.75–0.94, n = 3) and body mass index (RR for 5 kg/m2 increment: 0.64, 95% CI: 0.56–0.73, n = 8), and direct associations with intakes of processed meats (RR for 50 g/day increment: 1.59, 95% CI: 1.11–2.28, n = 3), processed and red meats (RR for 100 g/day increment: 1.37, 95% CI: 1.04–1.82, n = 3) and alcohol (RR for 10 g/day increment: 1.25, 95% CI: 1.12–1.41, n = 6). ConclusionsEvidence from cohort studies suggested a protective role of vegetables and body weight control in esophageal adenocarcinomas development. For squamous cell carcinomas, higher intakes of red and processed meats and alcohol may increase the risk, whereas fruits intak

Journal article

Schlesinger S, Chan DSM, Vingeliene S, Vieira AR, Abar L, Polemiti E, Stevens CAT, Greenwood DC, Aune D, Norat Tet al., 2017, Carbohydrates, glycemic index, glycemic load, and breast cancer risk: a systematic review and dose-response meta-analysis of prospective studies, NUTRITION REVIEWS, Vol: 75, Pages: 420-441, ISSN: 0029-6643

Context: The investigation of dose–response associations between carbohydrate intake, glycemic index, glycemic load, and risk of breast cancer stratified by menopausal status, hormone receptor status, and body mass index (BMI) remains inconclusive. Objective: A systematic review and dose–response meta-analyses was conducted to investigate these associations. Data Sources: As part of the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, PubMed was searched up to May 2015 for relevant studies on these associations. Study Selection: Prospective studies reporting associations between carbohydrate intake, glycemic index, or glycemic load and breast cancer risk were included. Data Extraction: Two investigators independently extracted data from included studies. Results: Random-effects models were used to summarize relative risks (RRs) and 95%CIs. Heterogeneity between subgroups, including menopausal status, hormone receptor status, and BMI was explored using meta-regression. Nineteen publications were included. The summary RRs (95%CIs) for breast cancer were 1.04 (1.00–1.07) per 10 units/d for glycemic index, 1.01 (0.98–1.04) per 50 units/d for glycemic load, and 1.00 (0.96–1.05) per 50 g/d for carbohydrate intake. For glycemic index, the association appeared slightly stronger among postmenopausal women (summary RR per 10 units/d, 1.06; 95%CI, 1.02–1.10) than among premenopausal women, though the difference was not statistically significant (Pheterogeneity = 0.15). Glycemic load and carbohydrate intake were positively associated with breast cancer among postmenopausal women with estrogen-negative tumors (summary RR for glycemic load, 1.28; 95%CI, 1.08–1.52; and summary RR for carbohydrates, 1.13; 95%CI, 1.02–1.25). No differences in BMI were detected. Conclusions: Menopausal and hormone receptor status, but not BMI, might be potential influencing factors for the associations

Journal article

Vieira AR, Abar L, Chan D, Vingeliene S, Polemiti E, Stevens C, Greenwood D, Norat Tet al., 2017, Foods and beverages and colorectal cancer risk: a systematic review and meta-analysis of cohort studies, an update of the evidence of the WCRF-AICR Continuous Update Project., Annals of Oncology, Vol: 28, Pages: 1788-1802, ISSN: 1569-8041

Objective: As part of the World Cancer Research Fund International Continuous Update Project, we updated the systematic review and meta-analysis of prospective studies to quantify the dose-response between foods and beverages intake and colorectal cancer risk. Data Sources: PubMed and several databases up to May 31 st 2015. Study selection: Prospective studies reporting adjusted relative risk estimates for the association of specific food groups and beverages and risk of colorectal, colon and rectal cancer. Data synthesis: Dose-response meta-analyses using random effect models to estimate summary relative risks (RRs). Results: Results: 400 individual study estimates from 111 unique cohort studies were included. Overall, the risk increase of colorectal cancer is 12% for each 100g/day increase of red and processed meat intake (95%CI=4-21%, I2 =70%, pheterogeneity (ph)<0.01) and 7% for 10 g/day increase of ethanol intake in alcoholic drinks (95%CI=5-9%, I2 =25%, ph =  0.21). Colorectal cancer risk decrease in 17% for each 90g/day increase of whole grains (95%CI=11-21%, I2 =0%, ph =  0.30, 6 studies). For each 400 g/day increase of dairy products intake (95%CI=10-17%, I2 =18%, ph =  0.27, 10 studies). Inverse associations were also observed for vegetables intake (RR per 100 g/day =0.98 (95%CI=0.96-0.99, I2 =0%, ph =  0.48, 11 studies) and for fish intake (RR for 100g/day=0.89(95%CI=0.80-0.99, I2 =0%, ph =  0.52, 11 studies), that were weak for vegetables and driven by one study for fish. Intakes of fruits, coffee, tea, cheese, poultry and legumes were not associated with colorectal cancer risk. Conclusions: Our results reinforce the evidence that high intake of red and processed meat and alcohol increase the risk of colorectal cancer. Milk and whole grains may have a protective role against colorectal cancer. The evidence for vegetables and fish was less convincing.

Journal article

Schlesinger S, Aleksandrova K, Abar L, Vieria AR, Vingeliene S, Polemiti E, Stevens CA, Greenwood DC, Chan DS, Aune D, Norat Tet al., 2017, Adult weight gain and colorectal adenomas - a systematic review and meta-analysis., Annals of Oncology, Vol: 28, ISSN: 1569-8041

Background: Colorectal adenomas are known as precursors for the majority of colorectal carcinomas. While weight gain during adulthood has been identified as a risk factor for colorectal cancer, the association is less clear for colorectal adenomas. We conducted a systematic review and meta-analysis to quantify the evidence on this association. Methods: : We searched MEDLINE up to September 2016 to identify observational (prospective, cross-sectional and retrospective) studies on weight gain during adulthood and colorectal adenoma occurrence and recurrence. We conducted meta-analysis on high weight gain versus stable weight, linear and non-linear dose-response meta-analyses to analyze the association. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a random effects model. Results: For colorectal adenoma occurrence, the summary OR was 1.39 (95% CI: 1.17-1.65; I 2 :43%, N =9 studies, cases=5,507) comparing high (midpoint: 17.4 kg) versus stable weight gain during adulthood and with each 5 kg weight gain the odds increased by 7% (2%-11%; I 2 :65%, N =7 studies). Although there was indication of non-linearity ( Pnon-linearity <0.001) there was an increased odds of colorectal adenoma throughout the whole range of weight gain. Three studies were identified investigating the association between weight gain and colorectal adenoma recurrence and data were limited to draw firm conclusions. Conclusions: Even a small amount of adult weight gain was related to a higher odds of colorectal adenoma occurrence. Our findings add to the benefits of weight control in adulthood regarding colorectal adenomas occurrence, which might be relevant for early prevention of colorectal cancer.

Journal article

Abar L, Vieira AR, Aune D, Stevens CH, Vingeliene S, Chan D, Norat Tet al., 2016, Blood concentrations of carotenoids and retinol and lung cancer risk: an update of the WCRF–AICR systematic review of published prospective studies, Cancer Medicine, Vol: 5, Pages: 2069-2083, ISSN: 2045-7634

Carotenoids and retinol are considered biomarkers of fruits and vegetables intake, and are of much interest because of their anti-inflammatory and antioxidant properties; however, there is inconsistent evidence regarding their protective effects against lung cancer. We conducted a meta-analysis of prospective studies of blood concentrations of carotenoids and retinol, and lung cancer risk. We identified relevant prospective studies published up to December 2014 by searching the PubMed and several other databases. We calculated summary estimates of lung cancer risk for the highest compared with lowest carotenoid and retinol concentrations and dose–response meta-analyses using random effects models. We used fractional polynomial models to assess potential nonlinear relationships. Seventeen prospective studies (18 publications) including 3603 cases and 458,434 participants were included in the meta-analysis. Blood concentrations of α-carotene, β-carotene, total carotenoids, and retinol were significantly inversely associated with lung cancer risk or mortality. The summary relative risk were 0.66 (95% confidence interval [CI]: 0.55–0.80) per 5 μg/100 mL of α-carotene (studies [n] = 5), 0.84 (95% CI: 0.76–0.94) per 20 μg/100 mL of β-carotene (n = 9), 0.66 (95% CI: 0.54–0.81) per 100 μg/100 mL of total carotenoids (n = 4), and 0.81 (95% CI: 0.73–0.90) per 70 μg/100 mL of retinol (n = 8). In stratified analysis by sex, the significant inverse associations for β-carotene and retinol were observed only in men and not in women. Nonlinear associations were observed for β-carotene, β-cryptoxanthin, and lycopene, with stronger associations observed at lower concentrations. There were not enough data to conduct stratified analyses by smoking. In conclusion, higher blood concentrations of several carotenoids and retinol are associated with reduced lung cancer risk. Further studies in never and former sm

Journal article

Vingeliene S, Chan DS, Aune D, Vieira AR, Polemiti E, Stevens C, Abar L, Rosenblatt DN, Greenwood DC, Norat Tet al., 2016, An update of the WCRF/AICR systematic literature review on esophageal and gastric cancers and citrus fruits intake., Cancer Causes & Control, Vol: 27, Pages: 837-851, ISSN: 1573-7225

PURPOSE: The 2007 World Cancer Research Fund/American Institute for Cancer Research expert report concluded that foods containing vitamin C probably protect against esophageal cancer and fruits probably protect against gastric cancer. Most of the previous evidence was from case-control studies, which may be affected by recall and selection biases. More recently, several cohort studies have examined these associations. We conducted a systematic literature review of prospective studies on citrus fruits intake and risk of esophageal and gastric cancers. METHODS: PubMed was searched for studies published until 1 March 2016. We calculated summary relative risks and 95 % confidence intervals (95 % CI) using random-effects models. RESULTS: With each 100 g/day increase of citrus fruits intake, a marginally significant decreased risk of esophageal cancer was observed (summary RR 0.86, 95 % CI 0.74-1.00, 1,057 cases, six studies). The associations were similar for squamous cell carcinoma (RR 0.87, 95 % CI 0.69-1.08, three studies) and esophageal adenocarcinoma (RR 0.93, 95 % CI 0.78-1.11, three studies). For gastric cancer, the nonsignificant inverse association was observed for gastric cardia cancer (RR 0.75, 95 % CI 0.55-1.01, three studies), but not for gastric non-cardia cancer (RR 1.02, 95 % CI 0.90-1.16, four studies). Consistent summary inverse associations were observed when comparing the highest with lowest intake, with statistically significant associations for esophageal (RR 0.77, 95 % CI 0.64-0.91, seven studies) and gastric cardia cancers (RR 0.62, 95 % CI 0.39-0.99, three studies). CONCLUSIONS: Citrus fruits may decrease the risk of esophageal and gastric cardia cancers, but further studies are needed.

Journal article

Vieira AR, Abar L, Vingeliene S, Chan DSM, Aune D, Navarro-Rosenblatt D, Stevens C, Greenwood D, Norat Tet al., 2015, Fruits, vegetables and lung cancer risk: a systematic review and meta-analysis, Annals of Oncology, Vol: 27, Pages: 81-96, ISSN: 1569-8041

Background Lung cancer is the most common cause of cancer death. Fruits and vegetables containing carotenoids and other antioxidants have been hypothesized to decrease lung cancer risk. As part of the World Cancer Research Fund International Continuous Update Project, we conducted a systematic review and meta-analysis of prospective studies.Methods We searched PubMed and several databases up to December 2014 for prospective studies. We conducted meta-analyses comparing the highest and lowest intakes and dose–response meta-analyses to estimate summary relative risks (RRs) and 95% confidence intervals (CIs), and examine possible non-linear associations. We combined results from the Pooling Project with the studies we identified to increase the statistical power of our analysis.Results When comparing the highest with the lowest intakes, the summary RR estimates were 0.86 [95% CI 0.78–0.94; n (studies) = 18] for fruits and vegetables, 0.92 (95% CI 0.87–0.97; n = 25) for vegetables and 0.82 (95% CI 0.76–0.89; n = 29) for fruits. The association with fruit and vegetable intake was marginally significant in current smokers and inverse but not significant in former or never smokers. Significant inverse dose–response associations were observed for each 100 g/day increase: for fruits and vegetables [RR: 0.96; 95% CI 0.94–0.98, I2 = 64%, n = 14, N (cases) = 9609], vegetables (RR: 0.94; 95% CI 0.89–0.98, I2 = 48%, n = 20, N = 12 563) and fruits (RR: 0.92; 95% CI 0.89–0.95, I2 = 57%, n = 23, N = 14 506). Our results were consistent among the different types of fruits and vegetables. The strength of the association differed across locations. There was evidence of a non-linear relationship (P < 0.01) between fruit and vegetable intake and lung cancer risk showing that no further benefit is obtained when increasing consumption above ∼400 g per day.Conclusions Eliminating tobacco smoking is the best strategy to prevent lung canc

Journal article

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