Imperial College London

ProfessorMarcGunter

Faculty of MedicineSchool of Public Health

Chair in Cancer Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 2623m.gunter

 
 
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Location

 

VC2Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

635 results found

Cairat M, Al Rahmoun M, Gunter MJ, Severi G, Dossus L, Fournier Aet al., 2020, Use of nonsteroidal anti-inflammatory drugs and breast cancer risk in a prospective cohort of postmenopausal women, BREAST CANCER RESEARCH, Vol: 22, ISSN: 1465-5411

Journal article

Jarvik GP, Wang X, Fontanillas P, Kim E, Chanprasert S, Gordon AS, Bastarache L, Kowdley K, Harrison T, Rosenthal EA, Stanaway IB, Bezieau S, Weinstein SJ, Newcomb PA, Casey G, Platz EA, Visvanathan K, Le Marchand L, Ulrich CM, Hardikar S, Li C, van Duijnhoven FJB, Gsur A, Campbell PT, Moreno V, Vodicka P, Brenner H, Chang-Claude J, Hoffmeister M, Slattery ML, Gunter MJ, Aglago EK, Castellvi-Bel S, Kweon S-S, Chan AT, Li L, Zheng W, Bishop DT, Giles GG, Rennert G, Offit K, Keku TO, Woods MO, Hampe J, Van Guelpen B, Gallinger SJ, de la Chapelle A, Hampel H, Berndt S, Tangen CM, Lindblom A, Wolk A, Burnett-Hartman A, Wu AH, White E, Gruber SB, Jenkins MA, Mountain J, Peters U, Crosslin DRet al., 2020, Hemochromatosis risk genotype is not associated with colorectal cancer or age at its diagnosis, HUMAN GENETICS AND GENOMICS ADVANCES, Vol: 1, ISSN: 2666-2477

Journal article

Sanikini H, Muller DC, Chadeau-Hyam M, Murphy N, Gunter MJ, Cross AJet al., 2020, Anthropometry, body fat composition and reproductive factors and risk of oesophageal and gastric cancer by subtype and subsite in the UK Biobank cohort, PLoS One, Vol: 15, Pages: 1-22, ISSN: 1932-6203

BackgroundObesity has been positively associated with upper gastrointestinal cancers, but prospective data by subtype/subsite are limited. Obesity influences hormonal factors, which may play a role in these cancers. We examined anthropometry, body fat and reproductive factors in relation to oesophageal and gastric cancer by subtype/subsite in the UK Biobank cohort.MethodsAmong 458,713 UK Biobank participants, 339 oesophageal adenocarcinomas, 124 oesophageal squamous cell carcinomas, 137 gastric cardia and 92 gastric non-cardia cancers were diagnosed during a mean of 6.5 years follow-up. Cox models estimated multivariable hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsBody mass index (BMI), hip circumference, waist circumference, waist-to-hip ratio, waist-to-height ratio, total body fat and trunk fat were positively associated with oesophageal adenocarcinoma (highest vs lowest category: HR = 2.33, 95%-CI:1.65–3.28; HR = 1.56, 95%-CI:1.15–2.13; HR = 2.30, 95%-CI:1.47–3.57; HR = 1.71, 95%-CI:1.01–2.90; HR = 2.87, 95%-CI:1.88–4.38; HR = 1.96, 95%-CI:1.30–2.96; HR = 2.34, 95%-CI:1.70–3.22, respectively). Although there were no statistically significant associations in combined sex analyses, BMI (HR = 1.83, 95%-CI:1.00–3.37), waist circumference (HR = 2.21, 95%-CI:1.27–3.84) and waist-to-hip ratio (HR = 1.92, 95%-CI:1.11–3.29) were associated with gastric cardia cancer in men; however, mutual adjustment attenuated the associations for BMI and waist-to-hip ratio. For oesophageal squamous cell carcinoma, statistically significant inverse associations were observed among women for BMI, hip circumference, waist circumference, waist-to-height ratio, total body fat and trunk fat, although they were based on small numbers. In addition, older age at first (HR = 0.44, 95%-CI:0.22–0.88) and last live birth (HR = 0.44, 95%-CI:0.22–0.87) were inversely associated with oesophageal squamous cell carc

Journal article

Aglago EK, Rinaldi S, Freisling H, Jiao L, Hughes DJ, Fedirko V, Schalkwijk CG, Weiderpass E, Dahm CC, Overvad K, Eriksen AK, Kyrø C, Boutron-Ruault M-C, Rothwell JA, Severi G, Katzke V, Kühn T, Schulze MB, Aleksandrova K, Masala G, Krogh V, Panico S, Tumino R, Naccarati A, Bueno-de-Mesquita B, van Gils CH, Sandanger TM, Gram IT, Skeie G, Quirós JR, Jakszyn P, Sánchez M-J, Amiano P, Huerta JM, Ardanaz E, Johansson I, Harlid S, Perez-Cornago A, Mayén A-L, Cordova R, Gunter MJ, Vineis P, Cross AJ, Riboli E, Jenab Met al., 2020, Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk: A Case-Control Study Nested within a European Prospective Cohort, Cancer Epidemiology, Biomarkers and Prevention, Vol: 30, ISSN: 1055-9965

BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation. METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively. RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99). CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk. IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.

Journal article

Hidaka A, Harrison TA, Cao Y, Sakoda LC, Barfield R, Giannakis M, Song M, Phipps A, Figueiredo JC, Zaidi SH, Toland AE, Amitay EL, Berndt S, Borozan I, Chan AT, Gallinger S, Gunter MJ, Guinter MA, Harlid S, Hampel H, Jenkins MA, Lin Y, Moreno V, Newcomb PA, Nishihara R, Ogino S, Obon-Santacana M, Parfrey PS, Potter JD, Slattery ML, Steinfelder RS, Um CY, Wang X, Woods MO, Van Guelpen B, Thibodeau SN, Hoffmeister M, Sun W, Hsu L, Buchanan DD, Campbell PT, Peters Uet al., 2020, Intake of Dietary Fruit, Vegetables, and Fiber and Risk of Colorectal Cancer According to Molecular Subtypes: A Pooled Analysis of 9 Studies, CANCER RESEARCH, Vol: 80, Pages: 4578-4590, ISSN: 0008-5472

Journal article

Idahl A, Le Cornet C, Maldonado SG, Waterboer T, Bender N, Tjonneland A, Hansen L, Boutron-Ruault M-C, Fournier A, Kvaskoff M, Boeing H, Trichopoulou A, Valanou E, Peppa E, Palli D, Agnoli C, Mattiello A, Tumino R, Sacerdote C, Onland-Moret NC, Gram IT, Weiderpass E, Quiros JR, Duell EJ, Sanchez M-J, Chirlaque M-D, Barricarte A, Gil L, Brandstedt J, Riesbeck K, Lundin E, Khaw K-T, Perez-Cornago A, Gunter MJ, Dossus L, Kaaks R, Fortner RTet al., 2020, Serologic markers of <i>Chlamydia trachomatis</i> and other sexually transmitted infections and subsequent ovarian cancer risk: Results from the EPIC cohort, INTERNATIONAL JOURNAL OF CANCER, Vol: 147, Pages: 2042-2052, ISSN: 0020-7136

Journal article

Dashti SG, English DR, Simpson JA, Karahalios A, Moreno-Betancur M, Biessy C, Rinaldi S, Ferrari P, Tjønneland A, Halkjær J, Dahm CC, Vistisen HT, Menegaux F, Perduca V, Severi G, Aleksandrova K, Schulze MB, Masala G, Sieri S, Tumino R, Macciotta A, Panico S, Hiensch AE, May AM, Quirós JR, Agudo A, Sánchez M-J, Amiano P, Colorado-Yohar S, Ardanaz E, Allen NE, Weiderpass E, Fortner RT, Christakoudi S, Tsilidis KK, Riboli E, Kaaks R, Gunter MJ, Viallon V, Dossus Let al., 2020, Adiposity and endometrial cancer risk in postmenopausal women: a sequential causal mediation analysis, Cancer Epidemiology, Biomarkers and Prevention, Vol: 30, Pages: 104-113, ISSN: 1055-9965

BACKGROUND: Adiposity increases endometrial cancer risk, possibly through inflammation, hyperinsulinemia, and increasing estrogens. We aimed to quantify the mediating effects of adiponectin (anti-inflammatory adipocytokine); IL6, IL1-receptor antagonist, TNF receptor 1 and 2, and C-reactive protein (inflammatory status biomarkers); C-peptide (hyperinsulinemia biomarker); and free estradiol and estrone (estrogen biomarkers) in the adiposity-endometrial cancer link in postmenopausal women. METHODS: We used data from a case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Eligible women did not have cancer, hysterectomy, and diabetes; did not use oral contraceptives or hormone therapy; and were postmenopausal at recruitment. Mediating pathways from adiposity to endometrial cancer were investigated by estimating natural indirect (NIE) and direct (NDE) effects using sequential mediation analysis. RESULTS: The study included 163 cases and 306 controls. The adjusted OR for endometrial cancer for body mass index (BMI) ≥30 versus ≥18.5-<25 kg/m2 was 2.51 (95% confidence interval, 1.26-5.02). The ORsNIE were 1.95 (1.01-3.74) through all biomarkers [72% proportion mediated (PM)] decomposed as: 1.35 (1.06-1.73) through pathways originating with adiponectin (33% PM); 1.13 (0.71-1.80) through inflammation beyond (the potential influence of) adiponectin (13% PM); 1.05 (0.88-1.24) through C-peptide beyond adiponectin and inflammation (5% PM); and 1.22 (0.89-1.67) through estrogens beyond preceding biomarkers (21% PM). The ORNDE not through biomarkers was 1.29 (0.54-3.09). Waist circumference gave similar results. CONCLUSIONS: Reduced adiponectin and increased inflammatory biomarkers, C-peptide, and estrogens mediated approximately 70% of increased odds of endometrial cancer in women with obesity versus normal weight. IMPACT: If replicated, these results could have implications for identifying targets for intervention to reduce e

Journal article

Naudin S, Viallon V, Hashim D, Freisling H, Jenab M, Weiderpass E, Perrier F, McKenzie F, Bueno-de-Mesquita HB, Olsen A, Tjønneland A, Dahm CC, Overvad K, Mancini FR, Rebours V, Boutron-Ruault M-C, Katzke V, Kaaks R, Bergmann M, Boeing H, Peppa E, Karakatsani A, Trichopoulou A, Pala V, Masala G, Panico S, Tumino R, Sacerdote C, May AM, van Gils CH, Rylander C, Borch KB, Chirlaque López MD, Sánchez M-J, Ardanaz E, Quirós JR, Amiano Exezarreta P, Sund M, Drake I, Regnér S, Travis RC, Wareham N, Aune D, Riboli E, Gunter MJ, Duell EJ, Brennan P, Ferrari Pet al., 2020, Healthy lifestyle and the risk of pancreatic cancer in the EPIC study, European Journal of Epidemiology, Vol: 35, Pages: 975-986, ISSN: 0393-2990

Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants' shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e-09) and 0.77 (0.72, 0.82; ptrend = 1.7e-15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e-04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.

Journal article

Dashti SG, Viallon V, Simpson JA, Karahalios A, Moreno-Betancur M, English DR, Gunter MJ, Murphy Net al., 2020, Explaining the link between adiposity and colorectal cancer risk in men and postmenopausal women in the UK Biobank: A sequential causal mediation analysis, INTERNATIONAL JOURNAL OF CANCER, Vol: 147, Pages: 1881-1894, ISSN: 0020-7136

Journal article

Labadie JD, Harrison TA, Banbury B, Amtay EL, Bernd S, Brenner H, Buchanan DD, Campbell PT, Cao Y, Chan AT, Chang-Claude J, English D, Figueiredo JC, Gallinger SJ, Giles GG, Gunter MJ, Hoffmeister M, Hsu L, Jenkins MA, Lin Y, Milne RL, Moreno V, Murphy N, Ogino S, Phipps A, Sakoda LC, Slattery ML, Southey MC, Sun W, Thibodeau SN, Van Guelpen B, Zaidi SH, Peters U, Newcomb PAet al., 2020, Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location, JNCI CANCER SPECTRUM, Vol: 4

Journal article

Huybrechts I, Zouiouich S, Loobuyck A, Vandenbulcke Z, Vogtmann E, Pisanu S, Iguacel I, Scalbert A, Indave I, Smelov V, Gunter MJ, Michels Net al., 2020, The Human Microbiome in Relation to Cancer Risk: A Systematic Review of Epidemiologic Studies, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 29, Pages: 1856-1868, ISSN: 1055-9965

Journal article

Deschasaux M, Huybrechts I, Julia C, Hercberg S, Egnell M, Srour B, Kesse-Guyot E, Latino-Martel P, Biessy C, Casagrande C, Murphy N, Jenab M, Ward HA, Weiderpass E, Overvad K, Tjønneland A, Rostgaard-Hansen AL, Boutron-Ruault M-C, Mancini FR, Mahamat-Saleh Y, Kühn T, Katzke V, Bergmann MM, Schulze MB, Trichopoulou A, Karakatsani A, Peppa E, Masala G, Agnoli C, De Magistris MS, Tumino R, Sacerdote C, Boer JM, Verschuren WM, van der Schouw YT, Skeie G, Braaten T, Redondo ML, Agudo A, Petrova D, Colorado-Yohar SM, Barricarte A, Amiano P, Sonestedt E, Ericson U, Otten J, Sundström B, Wareham NJ, Forouhi NG, Vineis P, Tsilidis KK, Knuppel A, Papier K, Ferrari P, Riboli E, Gunter MJ, Touvier Met al., 2020, Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality: EPIC cohort study in 10 European countries., BMJ, Vol: 370, Pages: 1-13, ISSN: 1759-2151

OBJECTIVE: To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality. DESIGN: Population based cohort study. SETTING: European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries. PARTICIPANTS: 521 324 adults; at recruitment, country specific and validated dietary questionnaires were used to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed. The higher the score the lower the overall nutritional quality of the diet. MAIN OUTCOME MEASURE: Associations between the FSAm-NPS dietary index score and mortality, assessed using multivariable adjusted Cox proportional hazards regression models. RESULTS: After exclusions, 501 594 adults (median follow-up 17.2 years, 8 162 730 person years) were included in the analyses. Those with a higher FSAm-NPS dietary index score (highest versus lowest fifth) showed an increased risk of all cause mortality (n=53 112 events from non-external causes; hazard ratio 1.07, 95% confidence interval 1.03 to 1.10, P<0.001 for trend) and mortality from cancer (1.08, 1.03 to 1.13, P<0.001 for trend) and diseases of the circulatory (1.04, 0.98 to 1.11, P=0.06 for trend), respiratory (1.39, 1.22 to 1.59, P<0.001), and digestive (1.22, 1.02 to 1.45, P=0.03 for trend) systems. The age standardised absolute rates for all cause mortality per 10 000 persons over 10 years were 760 (men=1237; women=563) for those in the highest fifth of the FSA

Journal article

Naudin S, Margalef MS, Hosnijeh FS, Nieters A, Kyro C, Tjonneland A, Dahm CC, Overvad K, Mahamat-Saleh Y, Besson C, Boutron-Ruault M-C, Kuehn T, Canzian F, Schulze MB, Peppa E, Karakatsani A, Trichopoulou A, Sieri S, Masala G, Panico S, Tumino R, Ricceri F, Chen SLF, Barroso LL, Huerta JM, Sanchez M-J, Ardanaz E, Menendez V, Exezarreta PA, Spaeth F, Jerkeman M, Jirstom K, Schmidt JA, Aune D, Weiderpass E, Riboli E, Vermeulen R, Casabonne D, Gunter M, Brennan P, Ferrari Pet al., 2020, Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study, International Journal of Cancer, Vol: 147, Pages: 1649-1656, ISSN: 0020-7136

Limited evidence exists on the role of modifiable lifestyle factors on the risk of lymphoma. In this work, the associations between adherence to healthy lifestyles and risks of Hodgkin lymphoma (HL) and non‐Hodgkin lymphoma (NHL) were evaluated in a large‐scale European prospective cohort. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 2,999 incident lymphoma cases (132 HL and 2,746 NHL) were diagnosed among 453,808 participants after 15 years (median) of follow‐up. The healthy lifestyle index (HLI) score combined information on smoking, alcohol intake, diet, physical activity and BMI, with large values of HLI expressing adherence to healthy behavior. Cox proportional hazards models were used to estimate lymphoma hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses were conducted by excluding, in turn, each lifestyle factor from the HLI score. The HLI was inversely associated with HL, with HR for a 1‐standard deviation (SD) increment in the score equal to 0.78 (95% CI: 0.66, 0.94). Sensitivity analyses showed that the association was mainly driven by smoking and marginally by diet. NHL risk was not associated with the HLI, with HRs for a 1‐SD increment equal to 0.99 (0.95, 1.03), with no evidence for heterogeneity in the association across NHL subtypes. In the EPIC study, adherence to healthy lifestyles was not associated with overall lymphoma or NHL risk, while an inverse association was observed for HL, although this was largely attributable to smoking. These findings suggest a limited role of lifestyle factors in the etiology of lymphoma subtypes.

Journal article

Knuppel A, Fensom GK, Watts EL, Gunter MJ, Murphy N, Papier K, Perez-Cornago A, Schmidt JA, Byrne KS, Travis RC, Key TJet al., 2020, Circulating Insulin-like Growth Factor-I Concentrations and Risk of 30 Cancers: Prospective Analyses in UK Biobank, CANCER RESEARCH, Vol: 80, Pages: 4014-4021, ISSN: 0008-5472

Journal article

Thomas M, Sakoda LC, Hoffmeister M, Rosenthal EA, Lee JK, van Duijnhoven FJB, Platz EA, Wu AH, Dampier CH, de la Chapelle A, Wolk A, Joshi AD, Burnett-Hartman A, Gsur A, Lindblom A, Castells A, Win AK, Namjou B, Van Guelpen B, Tangen CM, He Q, Li C, Schafmayer C, Joshu CE, Ulrich CM, Bishop DT, Buchanan DD, Schaid D, Drew DA, Muller DC, Duggan D, Crosslin DR, Albanes D, Giovannucci EL, Larson E, Qu F, Mentch F, Giles GG, Hakonarson H, Hampel H, Stanaway IB, Figueiredo JC, Huyghe JR, Minnier J, Chang-Claude J, Hampe J, Harley JB, Visvanathan K, Curtis KR, Offit K, Li L, Le Marchand L, Vodickova L, Gunter MJ, Jenkins MA, Slattery ML, Lemire M, Woods MO, Song M, Murphy N, Lindor NM, Dikilitas O, Pharoah PDP, Campbell PT, Newcomb PA, Milne RL, MacInnis RJ, Castellvi-Bel S, Ogino S, Berndt S, Bezieau S, Thibodeau SN, Gallinger SJ, Zaidi SH, Harrison TA, Keku TO, Hudson TJ, Vymetalkova V, Moreno V, Martin V, Arndt V, Wei W-Q, Chung W, Su Y-R, Hayes RB, White E, Vodicka P, Casey G, Gruber SB, Schoen RE, Chan AT, Potter JD, Brenner H, Jarvik GP, Corley DA, Peters U, Hsu Let al., 2020, Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 107, Pages: 432-444, ISSN: 0002-9297

Journal article

Bueno-de-Mesquita B, Cross A, Aune D, Tsilidis Ket al., 2020, Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses, BMC Medicine, Vol: 18, Pages: 1-15, ISSN: 1741-7015

BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported antioxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5x10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity=0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin, were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P=0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P=0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were

Journal article

Fortner RT, Huesing A, Dossus L, Tjonneland A, Overvad K, Dahm CC, Arveux P, Fournier A, Kvaskoff M, Schulze MB, Bergmann M, Trichopoulou A, Karakatsani A, La Vecchia C, Masala G, Pala V, Mattiello A, Tumino R, Ricceri F, van Gils CH, Monninkhof EM, Bonet C, Quiros JR, Sanchez M-J, Rodriguez-Palacios D-A, Gurrea AB, Amiano P, Allen NE, Travis RC, Gunter MJ, Viallon V, Weiderpass E, Riboli E, Kaaks Ret al., 2020, Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort, INTERNATIONAL JOURNAL OF CANCER, Vol: 147, Pages: 1325-1333, ISSN: 0020-7136

Journal article

Casabonne D, Benavente Y, Seifert J, Costas L, Armesto M, Arestin M, Besson C, Hosnijeh FS, Duell EJ, Weiderpass E, Masala G, Kaaks R, Canzian F, Chirlaque M-D, Perduca V, Mancini FR, Pala V, Trichopoulou A, Karakatsani A, La Vecchia C, Sánchez M-J, Tumino R, Gunter MJ, Amiano P, Panico S, Sacerdote C, Schmidt JA, Boeing H, Schulze MB, Barricarte A, Riboli E, Olsen A, Tjønneland A, Vermeulen R, Nieters A, Lawrie CH, de Sanjosé Set al., 2020, Serum levels of hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p and subsequent risk of chronic lymphocytic leukemia in the EPIC study, International Journal of Cancer, Vol: 147, Pages: 1315-1324, ISSN: 0020-7136

Chronic lymphocytic leukemia (CLL) is an incurable disease accounting for almost one-third of leukemias in the Western world. Aberrant expression of microRNAs (miRNAs) is a well-established characteristic of CLL, and the robust nature of miRNAs makes them eminently suitable liquid biopsy biomarkers. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC), the predictive values of five promising human miRNAs (hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p), identified in a pilot study, were examined in serum of 224 CLL cases (diagnosed 3 months to 18 years after enrollment) and 224 matched controls using Taqman based assays. Conditional logistic regressions were applied to adjust for potential confounders. The median time from blood collection to CLL diagnosis was 10 years (p25-p75: 7-13 years). Overall, the upregulation of hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p was associated with subsequent risk of CLL [OR1∆Ct-unit increase (95%CI) = 1.42 (1.18-1.72), 1.64 (1.31-2.04) and 1.75 (1.31-2.34) for hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p, respectively] and the strongest associations were observed within 10 years of diagnosis. However, the predictive performance of these miRNAs was modest (area under the curve <0.62). hsa-miR-16-5p and hsa-miR-223-3p levels were unrelated to CLL risk. The findings of this first prospective study suggest that hsa-miR-29a, hsa-miR-150-5p and hsa-miR-155-5p were upregulated in early stages of CLL but were modest predictive biomarkers of CLL risk.

Journal article

Yammine S, Huybrechts I, Biessy C, Dossus L, Aglago EK, Naudin S, Ferrari P, Weiderpass E, Tjonneland A, Hansen L, Overvad K, Mancini FR, Boutron-Ruault M-C, Kvaskoff M, Fortner RT, Kaaks R, Schulze MB, Boeing H, Trichopoulou A, Karakatsani A, La Vecchia C, Benetou V, Masala G, Krogh V, Mattiello A, Macciotta A, Gram IT, Skeie G, Quiros JR, Agudo A, Sanchez M-J, Chirlaque M-D, Ardanaz E, Gil L, Sartor H, Drake I, Idahl A, Lundin E, Aune D, Ward H, Merritt MA, Allen NE, Gunter MJ, Chajes Vet al., 2020, Dietary and Circulating Fatty Acids and Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 29, Pages: 1739-1749, ISSN: 1055-9965

Journal article

Jakszyn P, Cayssials V, Buckland G, Perez-Cornago A, Weiderpass E, Boeing H, Bergmann MM, Vulcan A, Ohlsson B, Masala G, Cross AJ, Riboli E, Ricceri F, Dahm C, Nyvang D, Katzke VA, Kühns T, Kyrø C, Tjønneland A, Ward HA, Tsilidis KK, Skeie G, Sieri S, Sanchez MJ, Huerta JM, Amiano P, Lasheras C, Ardanaz E, Mahamat-Saleh Y, Boutron-Ruault MC, Carbonnel F, Panico S, Peppa E, Trichopoulou A, Karakatsani A, Tumino R, Vermeulen R, Jenab M, Gunter M, Agudo Aet al., 2020, Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, International Journal of Cancer, Vol: 147, Pages: 1027-1039, ISSN: 0020-7136

Pro-inflammatory diets are associated with risk of developing colorectal cancer (CRC), however inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute towards a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumours). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More pro- inflammatory diets were related to a higher CRC risk, particularly for colon cancer; Hazar Ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval (CI) 1.04-1.27) for CRC, 1.24 (95% CI 1.09-1.41) for colon cancer and 0.99 (95% CI 0.83-1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS were 1.62 (95% CI 1.31- 2.01) for colon cancer overall and 2.11 (95% CI 1.50-2.97) for colon cancer in men. This study shows that more pro-inflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men. This article is protected by copyright. All rights reserved.

Journal article

Pan K, Chlebowski RT, Mortimer JE, Gunther MJ, Rohan T, Vitolins MZ, Adams-Campbell LL, Ho GYF, Cheng T-YD, Nelson RAet al., 2020, Insulin resistance and breast cancer incidence and mortality in postmenopausal women in the Women's Health Initiative, CANCER, Vol: 126, Pages: 3638-3647, ISSN: 0008-543X

Journal article

Kliemann N, Murphy N, Viallon V, Freisling H, Tsilidis KK, Rinaldi S, Mancini FR, Fagherazzi G, Boutron-Ruault M-C, Boeing H, Schulze MB, Masala G, Krogh V, Sacerdote C, Santucci de Magistris M, Bueno-de-Mesquita B, Weiderpass E, Kühn T, Kaaks R, Jakszyn P, Redondo-Sánchez D, Amiano P, Chirlaque M-D, Barricarte Gurrea A, Ericson U, Drake I, Nøst TH, Aune D, May AM, Tjønneland A, Dahm CC, Overvad K, Tumino R, Ramón Quirós J, Trichopoulou A, Karakatsani A, La Vecchia C, Nilsson LM, Riboli E, Huybrechts I, Gunter MJet al., 2020, Predicted Basal metabolic rate and cancer risk in the European Prospective Investigation into Cancer and Nutrition (Epic), International Journal of Cancer, Vol: 147, Pages: 648-661, ISSN: 0020-7136

Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of estimated BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition. Estimated BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (Hazard Ratio per 1-standard deviation change in BMR [HR1-sd ]: 2.46; 95%CI 1.20; 5.03), and distal colon cancer (HR1-sd : 1.33; 95%CI 1.001; 1.77) among men, and with proximal colon (HR1-sd : 1.16; 95%CI 1.01; 1.35), pancreatic (HR1-sd : 1.37; 95%CI 1.13; 1.66), thyroid (HR1-sd : 1.65; 95%CI 1.33; 2.05), postmenopausal breast (HR1-sd : 1.17; 95%CI 1.11; 1.22), and endometrial (HR1-sd : 1.20; 95%CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness. This article is protected by copyright. All rights reserved.

Journal article

Lujan-Barroso L, Botteri E, Caini S, Ljungberg B, Roswall N, Tjønneland A, Bueno-de-Mesquita B, Gram IT, Tumino R, Kiemeney LA, Liedberg F, Stocks T, Gunter MJ, Murphy N, Cervenka I, Fournier A, Kvaskoff M, Häggström C, Overvad K, Lund E, Waaseth M, Fortner RT, Kühn T, Menéndez V, Sánchez M-J, Santiuste C, Perez-Cornago A, Zamora-Ros R, Cross AJ, Trichopoulou A, Karakatsani A, Peppa E, Palli D, Krogh V, Sciannameo V, Mattiello A, Panico S, van Gils CH, Onland-Moret NC, Barricarte A, Amiano P, Khaw K-T, Boeing H, Weiderpass E, Duell EJet al., 2020, Menstrual factors, reproductive history, hormone use, and urothelial carcinoma risk: a prospective study in the EPIC cohort, Cancer Epidemiology, Biomarkers and Prevention, Vol: 29, Pages: 1654-1664, ISSN: 1055-9965

BACKGROUND: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. METHODS: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non-muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models. RESULTS: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 = 0.48; 0.25-0.90; Ptrend in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03-1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non-muscle-invasive urothelial carcinoma risk was observed. CONCLUSIONS: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk. IMPACT: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.

Journal article

Wedekind R, Kiss A, Keski-Rahkonen P, Viallon V, Rothwell JA, Cross AJ, Rostgaard-Hansen AL, Sandanger TM, Jakszyn P, Schmidt JA, Pala V, Vermeulen R, Schulze MB, Kühn T, Johnson T, Trichopoulou A, Peppa E, La Vechia C, Masala G, Tumino R, Sacerdote C, Wittenbecher C, de Magistris MS, Dahm CC, Severi G, Mancini FR, Weiderpass E, Gunter MJ, Huybrechts I, Scalbert Aet al., 2020, A metabolomic study of red and processed meat intake and acylcarnitine concentrations in human urine and blood, American Journal of Clinical Nutrition, Vol: 112, Pages: 381-388, ISSN: 0002-9165

BACKGROUND: Acylcarnitines (ACs) play a major role in fatty acid metabolism and are potential markers of metabolic dysfunction with higher blood concentrations reported in obese and diabetic individuals. Diet, and in particular red and processed meat intake, has been shown to influence AC concentrations but data on the effect of meat consumption on AC concentrations is limited. OBJECTIVES: To investigate the effect of red and processed meat intake on AC concentrations in plasma and urine using a randomized controlled trial with replication in an observational cohort. METHODS: In the randomized crossover trial, 12 volunteers successively consumed 2 different diets containing either pork or tofu for 3 d each. A panel of 44 ACs including several oxidized ACs was analyzed by LC-MS in plasma and urine samples collected after the 3-d period. ACs that were associated with pork intake were then measured in urine (n = 474) and serum samples (n = 451) from the European Prospective Investigation into Cancer and nutrition (EPIC) study and tested for associations with habitual red and processed meat intake derived from dietary questionnaires. RESULTS: In urine samples from the intervention study, pork intake was positively associated with concentrations of 18 short- and medium-chain ACs. Eleven of these were also positively associated with habitual red and processed meat intake in the EPIC cross-sectional study. In blood, C18:0 was positively associated with red meat intake in both the intervention study (q = 0.004, Student's t-test) and the cross-sectional study (q = 0.033, linear regression). CONCLUSIONS: AC concentrations in urine and blood were associated with red meat intake in both a highly controlled intervention study and in subjects of a cross-sectional study. Our data on the role of meat intake on this important pathway of fatty acid and energy metabolism may help understanding the role of red meat consumption in the etiology of

Journal article

Dooley J, Lagou V, Goveia J, Ulrich A, Rohlenova K, Heirman N, Karakach T, Lampi Y, Khan S, Wang J, Dresselaers T, Himmelreich U, Gunter MJ, Prokopenko I, Carmeliet P, Liston Aet al., 2020, Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility, CELL REPORTS, Vol: 32, ISSN: 2211-1247

Journal article

Zheng J-S, Sharp SJ, Imamura F, Chowdhury R, Gundersen TE, Steur M, Sluijs I, Schouw YTVD, Agudo A, Aune D, Barricarte A, Boeing H, Chirlaque M-D, Dorronsoro M, Freisling H, El-Fatouhi D, Franks PW, Fagherazzi G, Grioni S, Gunter MJ, Kyro C, Katzke V, Kuhn T, Khaw K-T, Laouali N, Masala G, Nilsson PM, Overvad K, Panico S, Papier K, Quiros JR, Rolandsson O, Redondo-Sanchez D, Ricceri F, Schulze MB, Spijkerman AMW, Tjonneland A, Tong TYN, Tumino R, Weiderpass E, John D, Butterworth AS, Riboli E, Forouhi NG, Wareham NJet al., 2020, Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries, BMJ: British Medical Journal, Vol: 370, ISSN: 0959-535X

Objective To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.Design Prospective case-cohort study.Setting Populations from eight European countries.Participants 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.Main outcome measure Incident type 2 diabetes.Results In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.Conclusions These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are ob

Journal article

Claeys L, Romano C, De Ruyck K, Wilson H, Fervers B, Korenjak M, Zavadil J, Gunter MJ, De Saeger S, De Boevre M, Huybrechts Iet al., 2020, Mycotoxin exposure and human cancer risk: A systematic review of epidemiological studies, COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY, Vol: 19, Pages: 1449-1464, ISSN: 1541-4337

Journal article

Khalis M, Dossus L, Rinaldi S, Biessy C, Moskal A, Charaka H, Fort E, His M, Mellas N, Nejjari C, Charbotel B, Soliman AS, Romieu I, Chajes V, Gunter MJ, Huybrechts I, El Rhazi Ket al., 2020, Body size, silhouette trajectory and the risk of breast cancer in a Moroccan case-control study, BREAST CANCER, Vol: 27, Pages: 748-758, ISSN: 1340-6868

Journal article

Bell JA, Bull CJ, Gunter MJ, Carslake D, Mahajan A, Davey Smith G, Timpson NJ, Vincent EEet al., 2020, Early Metabolic Features of Genetic Liability to Type 2 Diabetes: Cohort Study With Repeated Metabolomics Across Early Life, DIABETES CARE, Vol: 43, Pages: 1537-1545, ISSN: 0149-5992

Journal article

Butt J, Jenab M, Pawlita M, Tjonneland A, Kyrø C, Boutron-Ruault M-C, Carbonnel F, Dong C, Kaaks R, Kühn T, Boeing H, Schulze MB, Trichopoulou A, Karakatsani A, La Vecchia C, Palli D, Agnoli C, Tumino R, Sacerdote C, Panico S, Bueno-de-Mesquita B, Vermeulen R, Gram IT, Weiderpass E, Benjaminsen Borch K, Quirós JR, Agudo A, Rodríguez-Barranco M, Santiuste C, Ardanaz E, Van Guelpen B, Harlid S, Imaz L, Perez-Cornago A, Gunter MJ, Zouiouich S, Park JY, Riboli E, Cross AJ, Heath AK, Waterboer T, Hughes DJet al., 2020, Antibody responses to Helicobacter pylori and risk of developing colorectal cancer in a European cohort, Cancer Epidemiology, Biomarkers and Prevention, Vol: 29, Pages: 1475-1481, ISSN: 1055-9965

BACKGROUND: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer (CRC) development. However, prospective studies addressing H. pylori and CRC are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in pre-diagnostic serum samples from 485 CRC cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific sero-positivity with odds of developing CRC. RESULTS: Fifty-one percent of CRC cases were H. pylori sero-positive compared to 44% of controls resulting in an OR of 1.36 (95% CI: 1.00-1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by sero-positivity to Helicobacter cysteine-rich protein C (HcpC) (OR: 1.66, 95% CI: 1.19-2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34, 95% CI: 0.99-1.82), the latter being non-statistically significant only in the fully adjusted model. CONCLUSION: In this prospective multi-center European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing CRC. IMPACT: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease CRC incidence.

Journal article

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