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2016

The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort

Roura E., Travier N., Waterboer T., de Sanjose S., Bosch F. X., Pawlita M., Pala V., Weiderpass E., Margall N., Dillner J., Gram I. T., Tjonneland A., Munk C., Palli D., Khaw K. T., Overvad K., Clavel-Chapelon F., Mesrine S., Fournier A., Fortner R. T., Ose J., Steffen A., Trichopoulou A., Lagiou P., Orfanos P., Masala G., Tumino R., Sacerdote C., Polidoro S., Mattiello A., Lund E., Peeters P. H., Bueno-de-Mesquita H. B., Quiros J. R., Sanchez M. J., Navarro C., Barricarte A., Larranaga N., Ekstrom J., Lindquist D., Idahl A., Travis R. C., Merritt M. A., Gunter M. J., Rinaldi S., Tommasino M., Franceschi S., Riboli E., Castellsague X.

PLoS ONE; 2016; 11(1): e0147029

PMID:26808155

Abstract as provided by PubMed

BACKGROUND: In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). METHODS AND FINDINGS: We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for >/=15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). CONCLUSIONS: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.

Plasma concentrations and intakes of amino acids in male meat-eaters, fish-eaters, vegetarians and vegans: a cross-sectional analysis in the EPIC-Oxford cohort

Schmidt J. A., Rinaldi S., Scalbert A., Ferrari P., Achaintre D., Gunter M. J., Appleby P. N., Key T. J., Travis R. C.

Eur J Clin Nutr; 2016; 70(3): 306-12

PMID:26395436

Abstract as provided by PubMed

BACKGROUND/OBJECTIVES: We aimed to investigate the differences in plasma concentrations and in intakes of amino acids between male meat-eaters, fish-eaters, vegetarians and vegans in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. SUBJECTS/METHODS: This cross-sectional analysis included 392 men, aged 30-49 years. Plasma amino acid concentrations were measured with a targeted metabolomic approach using mass spectrometry, and dietary intake was assessed using a food frequency questionnaire. Differences between diet groups in mean plasma concentrations and intakes of amino acids were examined using analysis of variance, controlling for potential confounding factors and multiple testing. RESULTS: In plasma, concentrations of 6 out of 21 amino acids varied significantly by diet group, with differences of -13% to +16% between meat-eaters and vegans. Concentrations of methionine, tryptophan and tyrosine were highest in fish-eaters and vegetarians, followed by meat-eaters, and lowest in vegans. A broadly similar pattern was seen for lysine, whereas alanine concentration was highest in fish-eaters and lowest in meat-eaters. For glycine, vegans had the highest concentration and meat-eaters the lowest. Intakes of all 18 dietary amino acids differed by diet group; for the majority of these, intake was highest in meat-eaters followed by fish-eaters, then vegetarians and lowest in vegans (up to 47% lower than in meat-eaters). CONCLUSIONS: Men belonging to different habitual diet groups have significantly different plasma concentrations of lysine, methionine, tryptophan, alanine, glycine and tyrosine. However, the differences in plasma concentrations were less marked than and did not necessarily mirror those seen for amino acid intakes.

Consumption of soft drinks and juices and risk of liver and biliary tract cancers in a European cohort

Stepien M., Duarte-Salles T., Fedirko V., Trichopoulou A., Lagiou P., Bamia C., Overvad K., Tjonneland A., Hansen L., Boutron-Ruault M. C., Fagherazzi G., Severi G., Kuhn T., Kaaks R., Aleksandrova K., Boeing H., Klinaki E., Palli D., Grioni S., Panico S., Tumino R., Naccarati A., Bueno-de-Mesquita H. B., Peeters P. H., Skeie G., Weiderpass E., Parr C. L., Quiros J. R., Buckland G., Molina-Montes E., Amiano P., Chirlaque M. D., Ardanaz E., Sonestedt E., Ericson U., Wennberg M., Nilsson L. M., Khaw K. T., Wareham N., Bradbury K. E., Ward H. A., Romieu I., Jenab M.

Eur J Nutr; 2016; 55(1): 7-20

PMID:25528243

Abstract as provided by PubMed

PURPOSE: The aim of the study was to assess associations between intake of combined soft drinks (sugar sweetened and artificially sweetened) and fruit and vegetable juices and the risk of hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBC) and biliary tract cancers (GBTC) using data from the European Prospective Investigation into Cancer and Nutrition cohort of 477,206 participants from 10 European countries. METHODS: After 11.4 years of follow-up, 191 HCC, 66 IHBC and 236 GBTC cases were identified. Hazard ratios and 95 % confidence intervals (HR; 95 % CI) were estimated with Cox regression models with multivariable adjustment (baseline total energy intake, alcohol consumption and intake pattern, body mass index, physical activity, level of educational attainment and self-reported diabetes status). RESULTS: No risk associations were observed for IHBC or GBTC. Combined soft drinks consumption of >6 servings/week was positively associated with HCC risk: HR 1.83; 95 % CI 1.11-3.02, p trend = 0.01 versus non-consumers. In sub-group analyses available for 91 % of the cohort artificially sweetened soft drinks increased HCC risk by 6 % per 1 serving increment (HR 1.06, 95 % CI 1.03-1.09, n cases = 101); for sugar-sweetened soft drinks, this association was null (HR 1.00, 95 % CI 0.95-1.06; n cases = 127, p heterogeneity = 0.07). Juice consumption was not associated with HCC risk, except at very low intakes (<1 serving/week: HR 0.60; 95 % CI 0.38-0.95; p trend = 0.02 vs. non-consumers). CONCLUSIONS: Daily intake of combined soft drinks is positively associated with HCC, but a differential association between sugar and artificially sweetened cannot be discounted. This study provides some insight into possible associations of HCC with sugary drinks intake. Further exploration in other settings is required.

A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort

Terry K. L., Schock H., Fortner R. T., Husing A., Fichorova R. N., Yamamoto H. S., Vitonis A. F., Johnson T., Overvad K., Tjonneland A., Boutron-Ruault M. C., Mesrine S., Severi G., Dossus L., Rinaldi S., Boeing H., Benetou V., Lagiou P., Trichopoulou A., Krogh V., Kuhn E., Panico S., Bueno-de-Mesquita H. B., Onland-Moret N. C., Peeters P. H., Gram I. T., Weiderpass E., Duell E. J., Sanchez M. J., Ardanaz E., Etxezarreta N., Navarro C., Idahl A., Lundin E., Jirstrom K., Manjer J., Wareham N. J., Khaw K. T., Byrne K. S., Travis R. C., Gunter M. J., Merritt M. A., Riboli E., Cramer D. W., Kaaks R.

Clin Cancer Res; 2016; 22(18): 4664-75

PMID:27060155

Abstract as provided by PubMed

PURPOSE: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. EXPERIMENTAL DESIGN: We measured CA125, HE4, CA72.4, and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as area under the receiver operator curve (C-statistic) for each marker individually and in combination. In addition, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. RESULTS: We observed the best discrimination between cases and controls within 6 months of diagnosis for CA125 (C-statistic = 0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. CONCLUSIONS: CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early-stage cases. Clin Cancer Res; 22(18); 4664-75. (c)2016 AACRSee related commentary by Skates, p. 4542.

Pre-diagnostic meat and fibre intakes in relation to colorectal cancer survival in the European Prospective Investigation into Cancer and Nutrition

Ward H. A., Norat T., Overvad K., Dahm C. C., Bueno-de-Mesquita H. B., Jenab M., Fedirko V., van Duijnhoven F. J., Skeie G., Romaguera-Bosch D., Tjonneland A., Olsen A., Carbonnel F., Affret A., Boutron-Ruault M. C., Katzke V., Kuhn T., Aleksandrova K., Boeing H., Trichopoulou A., Lagiou P., Bamia C., Palli D., Sieri S., Tumino R., Naccarati A., Mattiello A., Peeters P. H., Weiderpass E., Asli L. A., Jakszyn P., Ramon Quiros J., Sanchez M. J., Dorronsoro M., Huerta J. M., Barricarte A., Jirstrom K., Ericson U., Johansson I., Gylling B., Bradbury K. E., Khaw K. T., Wareham N. J., Stepien M., Freisling H., Murphy N., Cross A. J., Riboli E.

Br J Nutr; 2016; 116(2): 316-25

PMID:27193442

Abstract as provided by PubMed

Improvements in colorectal cancer (CRC) detection and treatment have led to greater numbers of CRC survivors, for whom there is limited evidence on which to provide dietary guidelines to improve survival outcomes. Higher intake of red and processed meat and lower intake of fibre are associated with greater risk of developing CRC, but there is limited evidence regarding associations with survival after CRC diagnosis. Among 3789 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, pre-diagnostic consumption of red meat, processed meat, poultry and dietary fibre was examined in relation to CRC-specific mortality (n 1008) and all-cause mortality (n 1262) using multivariable Cox regression models, adjusted for CRC risk factors. Pre-diagnostic red meat, processed meat or fibre intakes (defined as quartiles and continuous grams per day) were not associated with CRC-specific or all-cause mortality among CRC survivors; however, a marginal trend across quartiles of processed meat in relation to CRC mortality was detected (P 0.053). Pre-diagnostic poultry intake was inversely associated with all-cause mortality among women (hazard ratio (HR)/20 g/d 0.92; 95 % CI 0.84, 1.00), but not among men (HR 1.00; 95 % CI 0.91, 1.09) (P for heterogeneity=0.10). Pre-diagnostic intake of red meat or fibre is not associated with CRC survival in the EPIC cohort. There is suggestive evidence of an association between poultry intake and all-cause mortality among female CRC survivors and between processed meat intake and CRC-specific mortality; however, further research using post-diagnostic dietary data is required to confirm this relationship.

Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study

Zamora-Ros R., Rinaldi S., Tsilidis K. K., Weiderpass E., Boutron-Ruault M. C., Rostgaard-Hansen A. L., Tjonneland A., Clavel-Chapelon F., Mesrine S., Katzke V. A., Kuhn T., Forster J., Boeing H., Trichopoulou A., Lagiou P., Klinaki E., Masala G., Sieri S., Ricceri F., Tumino R., Mattiello A., Peeters P. H., Bueno-de-Mesquita H. B., Engeset D., Skeie G., Arguelles M., Agudo A., Sanchez M. J., Chirlaque M. D., Barricarte A., Chamosa S., Almquist M., Tosovic A., Hennings J., Sandstrom M., Schmidt J. A., Khaw K. T., Wareham N. J., Cross A. J., Slimani N., Byrnes G., Romieu I., Riboli E., Franceschi S.

Int J Cancer; 2016; 138(1): 65-73

PMID:26190646

Abstract as provided by PubMed

Incidence rates of differentiated thyroid carcinoma (TC) have increased in many countries. Adiposity and dietary risk factors may play a role, but little is known on the influence of energy intake and macronutrient composition. The aim of this study was to investigate the associations between TC and the intake of energy, macronutrients, glycemic index (GI) and glycemic load in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,274 middle-age participants (70.2% women) from ten European countries. Dietary data were collected using country-specific validated dietary questionnaires. Total carbohydrates, proteins, fats, saturated, monounsaturated and polyunsaturated fats (PUFA), starch, sugar, and fiber were computed as g/1,000 kcal. Multivariable Cox regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence interval (CI) by intake quartile (Q). After a mean follow-up time of 11 years, differentiated TC was diagnosed in 556 participants (90% women). Overall, we found significant associations only with total energy (HRQ4 vs .Q1 , 1.29; 95% CI, 1.00-1.68) and PUFA intakes (HRQ4 vs .Q1 , 0.74; 95% CI, 0.57-0.95). However, the associations with starch and sugar intake and GI were significantly heterogeneous across body mass index (BMI) groups, i.e., positive associations with starch and GI were found in participants with a BMI >/= 25 and with sugar intake in those with BMI < 25. Moreover, inverse associations with starch and GI were observed in subjects with BMI < 25. In conclusion, our results suggest that high total energy and low PUFA intakes may increase the risk of differentiated TC. Positive associations with starch intake and GI in participants with BMI >/= 25 suggest that those persons may have a greater insulin response to high starch intake and GI than lean people.

Dietary polyphenol intake in Europe: the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Zamora-Ros R., Knaze V., Rothwell J. A., Hemon B., Moskal A., Overvad K., Tjonneland A., Kyro C., Fagherazzi G., Boutron-Ruault M. C., Touillaud M., Katzke V., Kuhn T., Boeing H., Forster J., Trichopoulou A., Valanou E., Peppa E., Palli D., Agnoli C., Ricceri F., Tumino R., de Magistris M. S., Peeters P. H., Bueno-de-Mesquita H. B., Engeset D., Skeie G., Hjartaker A., Menendez V., Agudo A., Molina-Montes E., Huerta J. M., Barricarte A., Amiano P., Sonestedt E., Nilsson L. M., Landberg R., Key T. J., Khaw K. T., Wareham N. J., Lu Y., Slimani N., Romieu I., Riboli E., Scalbert A.

Eur J Nutr; 2016; 55(4): 1359-75

PMID:26081647

Abstract as provided by PubMed

BACKGROUND/OBJECTIVES: Polyphenols are plant secondary metabolites with a large variability in their chemical structure and dietary occurrence that have been associated with some protective effects against several chronic diseases. To date, limited data exist on intake of polyphenols in populations. The current cross-sectional analysis aimed at estimating dietary intakes of all currently known individual polyphenols and total intake per class and subclass, and to identify their main food sources in the European Prospective Investigation into Cancer and Nutrition cohort. METHODS: Dietary data at baseline were collected using a standardized 24-h dietary recall software administered to 36,037 adult subjects. Dietary data were linked with Phenol-Explorer, a database with data on 502 individual polyphenols in 452 foods and data on polyphenol losses due to cooking and food processing. RESULTS: Mean total polyphenol intake was the highest in Aarhus-Denmark (1786 mg/day in men and 1626 mg/day in women) and the lowest in Greece (744 mg/day in men and 584 mg/day in women). When dividing the subjects into three regions, the highest intake of total polyphenols was observed in the UK health-conscious group, followed by non-Mediterranean (non-MED) and MED countries. The main polyphenol contributors were phenolic acids (52.5-56.9 %), except in men from MED countries and in the UK health-conscious group where they were flavonoids (49.1-61.7 %). Coffee, tea, and fruits were the most important food sources of total polyphenols. A total of 437 different individual polyphenols were consumed, including 94 consumed at a level >1 mg/day. The most abundant ones were the caffeoylquinic acids and the proanthocyanidin oligomers and polymers. CONCLUSION: This study describes the large number of dietary individual polyphenols consumed and the high variability of their intakes between European populations, particularly between MED and non-MED countries.

Urinary excretions of 34 dietary polyphenols and their associations with lifestyle factors in the EPIC cohort study

Zamora-Ros R., Achaintre D., Rothwell J. A., Rinaldi S., Assi N., Ferrari P., Leitzmann M., Boutron-Ruault M. C., Fagherazzi G., Auffret A., Kuhn T., Katzke V., Boeing H., Trichopoulou A., Naska A., Vasilopoulou E., Palli D., Grioni S., Mattiello A., Tumino R., Ricceri F., Slimani N., Romieu I., Scalbert A.

Sci Rep; 2016; 26905

PMID:27273479

Abstract as provided by PubMed

Urinary excretion of 34 dietary polyphenols and their variations according to diet and other lifestyle factors were measured by tandem mass spectrometry in 475 adult participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study. A single 24-hour urine sample was analysed for each subject from 4 European countries. The highest median levels were observed for phenolic acids such as 4-hydroxyphenylacetic acid (157 mumol/24 h), followed by 3-hydroxyphenylacetic, ferulic, vanillic and homovanillic acids (20-50 mumol/24 h). The lowest concentrations were observed for equol, apigenin and resveratrol (<0.1 mumol/24 h). Urinary polyphenols significantly varied by centre, followed by alcohol intake, sex, educational level, and energy intake. This variability is largely explained by geographical variations in the diet, as suggested by the high correlations (r > 0.5) observed between urinary polyphenols and the intake of their main food sources (e.g., resveratrol and gallic acid ethyl ester with red wine intake; caffeic, protocatechuic and ferulic acids with coffee consumption; and hesperetin and naringenin with citrus fruit intake). The large variations in urinary polyphenols observed are largely determined by food preferences. These polyphenol biomarkers should allow more accurate evaluation of the relationships between polyphenol exposure and the risk of chronic diseases in large epidemiological studies.

2015

A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk

Aleksandrova K., Chuang S.C., Boeing H., Zuo H., Tell G.S., Pischon T., Jenab M., Bueno-de-Mesquita B., Vollset S.E., Midttun O., Ueland P.M., Fedirko V., Johansson M., Weiderpass E., Severi G., Racine A., Boutron-Ruault M.C., Kaaks R., Kuhn T., Tjonneland A., Overvad K., Quiros J.R., Jakszyn P., Sanchez M.J., Dorronsoro M., Chirlaque M.D., Ardanaz E., Khaw K.T., Wareham N.J., Travis R.C., Trichopoulou A., Lagiou P., Trichopoulos D., Palli D., Sieri S., Tumino R., Panico S., May A.M., Palmqvist R., Ljuslinder I., Kong S.Y., Freisling H., Gunter M.J., Lu Y., Cross A.J., Riboli E., Vineis P.

J Natl Cancer Inst; 2015; 107(4):

PMID:25713165

Abstract as provided by PubMed

BACKGROUND: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. RESULTS: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P difference = .87) and after excluding case patients diagnosed within the first four follow-up years. CONCLUSIONS: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC

The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: data from the European Prospective Investigation into Cancer and Nutrition

Aleksandrova K., Bamia C., Drogan D., Lagiou P., Trichopoulou A., Jenab M., Fedirko V., Romieu I., Bueno-de-Mesquita H. B., Pischon T., Tsilidis K., Overvad K., Tjonneland A., Bouton-Ruault M. C., Dossus L., Racine A., Kaaks R., Kuhn T., Tsironis C., Papatesta E. M., Saitakis G., Palli D., Panico S., Grioni S., Tumino R., Vineis P., Peeters P. H., Weiderpass E., Lukic M., Braaten T., Quiros J. R., Lujan-Barroso L., Sanchez M. J., Chilarque M. D., Ardanas E., Dorronsoro M., Nilsson L. M., Sund M., Wallstrom P., Ohlsson B., Bradbury K. E., Khaw K. T., Wareham N., Stepien M., Duarte-Salles T., Assi N., Murphy N., Gunter M. J., Riboli E., Boeing H., Trichopoulos D.

Am J Clin Nutr; 2015; 102(6): 1498-508

PMID:26561631

Abstract as provided by PubMed

BACKGROUND: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. OBJECTIVE: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC). DESIGN: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. RESULTS: The multivariable-adjusted RR of having >/=4 cups (600 mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. CONCLUSION: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.

A statistical framework to model the meeting-in-the-middle principle using metabolomic data: application to hepatocellular carcinoma in the EPIC study

Assi N., Fages A., Vineis P., Chadeau-Hyam M., Stepien M., Duarte-Salles T., Byrnes G., Boumaza H., Knuppel S., Kuhn T., Palli D., Bamia C., Boshuizen H., Bonet C., Overvad K., Johansson M., Travis R., Gunter M. J., Lund E., Dossus L., Elena-Herrmann B., Riboli E., Jenab M., Viallon V., Ferrari P.

Mutagenesis; 2015; 30(6): 743-53

PMID:26130468

Abstract as provided by PubMed

Metabolomics is a potentially powerful tool for identification of biomarkers associated with lifestyle exposures and risk of various diseases. This is the rationale of the 'meeting-in-the-middle' concept, for which an analytical framework was developed in this study. In a nested case-control study on hepatocellular carcinoma (HCC) within the European Prospective Investigation into Cancer and nutrition (EPIC), serum (1)H nuclear magnetic resonance (NMR) spectra (800 MHz) were acquired for 114 cases and 222 matched controls. Through partial least square (PLS) analysis, 21 lifestyle variables (the 'predictors', including information on diet, anthropometry and clinical characteristics) were linked to a set of 285 metabolic variables (the 'responses'). The three resulting scores were related to HCC risk by means of conditional logistic regressions. The first PLS factor was not associated with HCC risk. The second PLS metabolomic factor was positively associated with tyrosine and glucose, and was related to a significantly increased HCC risk with OR = 1.11 (95% CI: 1.02, 1.22, P = 0.02) for a 1SD change in the responses score, and a similar association was found for the corresponding lifestyle component of the factor. The third PLS lifestyle factor was associated with lifetime alcohol consumption, hepatitis and smoking, and had negative loadings on vegetables intake. Its metabolomic counterpart displayed positive loadings on ethanol, glutamate and phenylalanine. These factors were positively and statistically significantly associated with HCC risk, with 1.37 (1.05, 1.79, P = 0.02) and 1.22 (1.04, 1.44, P = 0.01), respectively. Evidence of mediation was found in both the second and third PLS factors, where the metabolomic signals mediated the relation between the lifestyle component and HCC outcome. This study devised a way to bridge lifestyle variables to HCC risk through NMR metabolomics data. This implementation of the 'meeting-in-the-middle' approach finds natural applications in settings characterised by high-dimensional data, increasingly frequent in the omics generation.

Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: Multicentre, prospective cohort study

Bamia C., Lagiou P., Jenab M., Trichopoulou A., Fedirko V., Aleksandrova K., Pischon T., Overvad K., Olsen A., Tjonneland A., Boutron-Ruault M.C., Fagherazzi G., Racine A., Kuhn T., Boeing H., Floegel A., Benetou V., Palli D., Grioni S., Panico S., Tumino R., Vineis P., Bueno-de-Mesquita H.B., Dik V.K., Bhoo-Pathy N., Uiterwaal C.S., Weiderpass E., Lund E., Quiros J.R., Zamora-Ros R., Molina-Montes E., Chirlaque M.D., Ardanaz E., Dorronsoro M., Lindkvist B., Wallstrom P., Nilsson L.M., Sund M., Khaw K.T., Wareham N., Bradbury K.E., Travis R.C., Ferrari P., Duarte-Salles T., Stepien M., Gunter M., Murphy N., Riboli E., Trichopoulos D.

Int. J. Cancer; 2015; 136(8): 1899-1908

PMID:25219573

Abstract as provided by PubMed

Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow-up of 11 years. We calculated adjusted hazard ratios (HRs) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% [HR: 0.28; 95% confidence intervals (CIs): 0.16-0.50, p-trend < 0.001]. The corresponding association of tea with HCC risk was 0.41 (95% CI: 0.22-0.78, p-trend = 0.003). There was no compelling evidence of heterogeneity of these associations across strata of important HCC risk factors, including hepatitis B or hepatitis C status (available in a nested case-control study). The inverse, monotonic associations of coffee intake with HCC were apparent for caffeinated (p-trend = 0.009), but not decaffeinated (p-trend = 0.45) coffee for which, however, data were available for a fraction of subjects. Results from this multicentre, European cohort study strengthen the existing evidence regarding the inverse association between coffee/tea and HCC risk. Given the apparent lack of heterogeneity of these associations by HCC risk factors and that coffee/tea are universal exposures, our results could have important implications for high HCC risk subjects

Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study

Bamia C., Lagiou P., Jenab M., Aleksandrova K., Fedirko V., Trichopoulos D., Overvad K., Tjonneland A., Olsen A., Clavel-Chapelon F., Boutron-Ruault M.C., Kvaskoff M., Katzke V.A., Kuhn T., Boeing H., Nothlings U., Palli D., Sieri S., Panico S., Tumino R., Naccarati A., Bueno-de-Mesquita H.A., Peeters P.H., Weiderpass E., Skeie G., Quiros J.R., Agudo A., Chirlaque M.D., Sanchez M.J., Ardanaz E., Dorronsoro M., Ericson U., Nilsson L.M., Wennberg M., Khaw K.T., Wareham N., Key T.J., Travis R.C., Ferrari P., Stepien M., Duarte-Salles T., Norat T., Murphy N., Riboli E., Trichopoulou A.

Br J Cancer; 2015; 112(7): 1273-1282

PMID:25742480

Abstract as provided by PubMed

BACKGROUND: Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations. METHODS: In 486 799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes. RESULTS: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11. CONCLUSIONS: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease

Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study

Besevic J., Gunter M. J., Fortner R. T., Tsilidis K. K., Weiderpass E., Charlotte Onland-Moret N., Dossus L., Tjonneland A., Hansen L., Overvad K., Mesrine S., Baglietto L., Clavel-Chapelon F., Kaaks R., Aleksandrova K., Boeing H., Trichopoulou A., Lagiou P., Bamia C., Masala G., Agnoli C., Tumino R., Ricceri F., Panico S., Bueno-de-Mesquita H. A., Peeters P. H., Jareid M., Ramon Quiros J., Duell E. J., Sanchez M. J., Larranaga N., Chirlaque M. D., Barricarte A., Dias J. A., Sonestedt E., Idahl A., Lundin E., Wareham N. J., Khaw K. T., Travis R. C., Rinaldi S., Romieu I., Riboli E., Merritt M. A.

Br J Cancer; 2015; 113(11): 1622-31

PMID:26554655

Abstract as provided by PubMed

BACKGROUND: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521 330 total participants (approximately 370 000 women) aged 25-70 years at recruitment from 1992 to 2000. METHODS: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre. RESULTS: After a mean follow-up of 3.6 years (+/-3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR=0.80, 95% CI=0.62-1.03) and a significant survival benefit in long-term MHT users (5 years use vs never use, HR=0.70, 95% CI=0.50-0.99, Ptrend=0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk. CONCLUSIONS: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users.

Coffee and tea consumption and risk of pre- and postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study

Bhoo-Pathy N., Peeters P. H., Uiterwaal C. S., Bueno-de-Mesquita H. B., Bulgiba A. M., Bech B. H., Overvad K., Tjonneland A., Olsen A., Clavel-Chapelon F., Fagherazzi G., Perquier F., Teucher B., Kaaks R., Schutze M., Boeing H., Lagiou P., Orfanos P., Trichopoulou A., Agnoli C., Mattiello A., Palli D., Tumino R., Sacerdote C., van Duijnhoven F. J., Braaten T., Lund E., Skeie G., Redondo M. L., Buckland G., Perez M. J., Chirlaque M. D., Ardanaz E., Amiano P., Wirfalt E., Wallstrom P., Johansson I., Nilsson L. M., Khaw K. T., Wareham N., Allen N. E., Key T. J., Rinaldi S., Romieu I., Gallo V., Riboli E., van Gils C. H.

Breast Cancer Res; 2015; 15

PMID:25637171

Abstract as provided by PubMed

INTRODUCTION: Specific coffee subtypes and tea may impact risk of pre- and post-menopausal breast cancer differently. We investigated the association between coffee (total, caffeinated, decaffeinated) and tea intake and risk of breast cancer. METHODS: A total of 335,060 women participating in the European Prospective Investigation into Nutrition and Cancer (EPIC) Study, completed a dietary questionnaire from 1992 to 2000, and were followed-up until 2010 for incidence of breast cancer. Hazard ratios (HR) of breast cancer by country-specific, as well as cohort-wide categories of beverage intake were estimated. RESULTS: During an average follow-up of 11 years, 1064 premenopausal, and 9134 postmenopausal breast cancers were diagnosed. Caffeinated coffee intake was associated with lower risk of postmenopausal breast cancer: adjusted HR=0.90, 95% confidence interval (CI): 0.82 to 0.98, for high versus low consumption; Ptrend=0.029. While there was no significant effect modification by hormone receptor status (P=0.711), linear trend for lower risk of breast cancer with increasing caffeinated coffee intake was clearest for estrogen and progesterone receptor negative (ER-PR-), postmenopausal breast cancer (P=0.008). For every 100 ml increase in caffeinated coffee intake, the risk of ER-PR- breast cancer was lower by 4% (adjusted HR: 0.96, 95% CI: 0.93 to 1.00). Non-consumers of decaffeinated coffee had lower risk of postmenopausal breast cancer (adjusted HR=0.89; 95% CI: 0.80 to 0.99) compared to low consumers, without evidence of dose-response relationship (Ptrend=0.128). Exclusive decaffeinated coffee consumption was not related to postmenopausal breast cancer risk, compared to any decaffeinated-low caffeinated intake (adjusted HR=0.97; 95% CI: 0.82 to 1.14), or to no intake of any coffee (HR: 0.96; 95%: 0.82 to 1.14). Caffeinated and decaffeinated coffee were not associated with premenopausal breast cancer. Tea intake was neither associated with pre- nor post-menopausal breast cancer. CONCLUSIONS: Higher caffeinated coffee intake may be associated with lower risk of postmenopausal breast cancer. Decaffeinated coffee intake does not seem to be associated with breast cancer.

Diabetes and Onset of Natural Menopause: Results From the European Prospective Investigation Into Cancer and Nutrition EDITORIAL COMMENT

Brand J.S., Onland-Moret N.C., Eijkemans M.J.C., Tjonneland A., Roswall N., Overvad K., Fagherazzi G., Clavel-Chapelon F., Dossus L., Lukanova A., Grote V., Bergman M.M., Boeing H., Trichoupoulou A., Tzivoglou M., Trichopoulos D., Grioni S., Mattiello A., Masala G., Tumino R., Vineis P., Bueno-de-Mesquit H.B., Weiderpass E., Redondo M.L., Sanchez M.J., Castano J.M.H., Arriola L., Ardanaz E., Duell E.J., Rolandsson O., Franks P.W., Butt S., Nilsson P., Khaw K.T., Wareham N., Travis R., Romieu I., Gunter M.J., Riboli E., van der Schouw Y.T.

Obstet Gynecol Surv; 2015; 70(8): 507-508
Diabetes and onset of natural menopause: results from the European Prospective Investigation into Cancer and Nutrition

Brand J.S., Onland-Moret N.C., Eijkemans M.J., Tjonneland A., Roswall N., Overvad K., Fagherazzi G., Clavel-Chapelon F., Dossus L., Lukanova A., Grote V., Bergmann M.M., Boeing H., Trichopoulou A., Tzivoglou M., Trichopoulos D., Grioni S., Mattiello A., Masala G., Tumino R., Vineis P., Bueno-de-Mesquita H.B., Weiderpass E., Redondo M.L., Sanchez M.J., Castano J.M., Arriola L., Ardanaz E., Duell E.J., Rolandsson O., Franks P.W., Butt S., Nilsson P., Khaw K.T., Wareham N., Travis R., Romieu I., Gunter M.J., Riboli E., van der Schouw Y.T.

Hum. Reprod; 2015; 30(6): 1491-1498

PMID:25779698

Abstract as provided by PubMed

STUDY QUESTION: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? SUMMARY ANSWER: Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause. WHAT IS KNOWN ALREADY: Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health. STUDY DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000. PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM. LIMITATIONS, REASONS FOR CAUTION: Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes. WIDER IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association. STUDY FUNDING/COMPETING INTERESTS: The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ) and Federal Ministry of Education and Research (BMMF) (Germany); Ministry of Health and Social Solidarity, Stavros Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skane and Vasterbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). None of the authors reported a conflict of interest

Healthy lifestyle index and risk of gastric adenocarcinoma in the EPIC cohort study

Buckland G., Travier N., Huerta J.M., Bueno-de-Mesquita H.B., Siersema P.D., Skeie G., Weiderpass E., Engeset D., Ericson U., Ohlsson B., Agudo A., Romieu I., Ferrari P., Freisling H., Colorado-Yohar S., Li K., Kaaks R., Pala V., Cross A.J., Riboli E., Trichopoulou A., Lagiou P., Bamia C., Boutron-Ruault M.C., Fagherazzi G., Dartois L., May A.M., Peeters P.H., Panico S., Johansson M., Wallner B., Palli D., Key T.J., Khaw K.T., Ardanaz E., Overvad K., Tjonneland A., Dorronsoro M., Sanchez M.J., Quiros J.R., Naccarati A., Tumino R., Boeing H., Gonzalez C.A.

Int. J Cancer; 2015; 137(3): 598-606

PMID:25557932

Abstract as provided by PubMed

Several modifiable lifestyle factors, including smoking, alcohol, certain dietary factors and weight are independently associated with gastric cancer (GC); however, their combined impact on GC risk is unknown. We constructed a healthy lifestyle index to investigate the joint influence of these behaviors on GC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The analysis included 461,550 participants (662 first incident GC cases) with a mean follow-up of 11.4 years. A healthy lifestyle index was constructed, assigning 1 point for each healthy behavior related to smoking status, alcohol consumption and diet quality (represented by the Mediterranean diet) for assessing overall GC and also body mass index for cardia GC and 0 points otherwise. Risk of GC was calculated using Cox proportional hazards regression models while adjusting for relevant confounders. The highest versus lowest score in the healthy lifestyle index was associated with a significant lower risk of GC, by 51% overall (HR 0.49 95% CI 0.35, 0.70), by 77% for cardia GC (HR 0.23 95% CI 0.08, 0.68) and by 47% for noncardia GC (HR 0.53 (95% CI 0.32, 0.87), p-trends<0.001. Population attributable risk calculations showed that 18.8% of all GC and 62.4% of cardia GC cases could have been prevented if participants in this population had followed the healthy lifestyle behaviors of this index. Adopting several healthy lifestyle behaviors including not smoking, limiting alcohol consumption, eating a healthy diet and maintaining a normal weight is associated with a large decreased risk of GC

Consumption of fatty foods and incident type 2 diabetes in populations from eight European countries

Buijsse B., Boeing H., Drogan D., Schulze M.B., Feskens E.J., Amiano P., Barricarte A., Clavel-Chapelon F., de Lauzon-Guillain B., Fagherazzi G., Fonseca-Nunes A., Franks P.W., Huerta J.M., Jakobsen M.U., Kaaks R., Key T.J., Khaw K.T., Masala G., Moskal A., Nilsson P.M., Overvad K., Pala V., Panico S., Redondo M.L., Ricceri F., Rolandsson O., Sanchez M.J., Sluijs I., Spijkerman A.M., Tjonneland A., Tumino R., van der A.DL, van der Schouw Y.T., Langenberg C., Sharp S.J., Forouhi N.G., Riboli E., Wareham N.J.

Eur. J Clin. Nutr; 2015; 69(4): 455-461

PMID:25424603

Abstract as provided by PubMed

BACKGROUND/OBJECTIVES: Diets high in saturated and trans fat and low in unsaturated fat may increase type 2 diabetes (T2D) risk, but studies on foods high in fat per unit weight are sparse. We assessed whether the intake of vegetable oil, butter, margarine, nuts and seeds and cakes and cookies is related to incident T2D. SUBJECTS/METHODS: A case-cohort study was conducted, nested within eight countries of the European Prospective Investigation into Cancer (EPIC), with 12,403 incident T2D cases and a subcohort of 16,835 people, identified from a cohort of 340,234 people. Diet was assessed at baseline (1991-1999) by country-specific questionnaires. Country-specific hazard ratios (HRs) across four categories of fatty foods (nonconsumers and tertiles among consumers) were combined with random-effects meta-analysis. RESULTS: After adjustment not including body mass index (BMI), nonconsumers of butter, nuts and seeds and cakes and cookies were at higher T2D risk compared with the middle tertile of consumption. Among consumers, cakes and cookies were inversely related to T2D (HRs across increasing tertiles 1.14, 1.00 and 0.92, respectively; P-trend <0.0001). All these associations attenuated upon adjustment for BMI, except the higher risk of nonconsumers of cakes and cookies (HR 1.57). Higher consumption of margarine became positively associated after BMI adjustment (HRs across increasing consumption tertiles: 0.93, 1.00 and 1.12; P-trend 0.03). Within consumers, vegetable oil, butter and nuts and seeds were unrelated to T2D. CONCLUSIONS: Fatty foods were generally not associated with T2D, apart from weak positive association for margarine. The higher risk among nonconsumers of cakes and cookies needs further explanation

Reliability of Serum Metabolites over a Two-Year Period: A Targeted Metabolomic Approach in Fasting and Non-Fasting Samples from EPIC

Carayol M., Licaj I., Achaintre D., Sacerdote C., Vineis P., Key T.J., Onland Moret N.C., Scalbert A., Rinaldi S., Ferrari P.

PLoS. One; 2015; 10(8): e0135437

PMID:26274920

Abstract as provided by PubMed

OBJECTIVE: Although metabolic profiles have been associated with chronic disease risk, lack of temporal stability of metabolite levels could limit their use in epidemiological investigations. The present study aims to evaluate the reliability over a two-year period of 158 metabolites and compare reliability over time in fasting and non-fasting serum samples. METHODS: Metabolites were measured with the AbsolueIDQp180 kit (Biocrates, Innsbruck, Austria) by mass spectrometry and included acylcarnitines, amino acids, biogenic amines, hexoses, phosphatidylcholines and sphingomyelins. Measurements were performed on repeat serum samples collected two years apart in 27 fasting men from Turin, Italy, and 39 non-fasting women from Utrecht, The Netherlands, all participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Reproducibility was assessed by estimating intraclass correlation coefficients (ICCs) in multivariable mixed models. RESULTS: In fasting samples, a median ICC of 0.70 was observed. ICC values were <0.50 for 48% of amino acids, 27% of acylcarnitines, 18% of lysophosphatidylcholines and 4% of phosphatidylcholines. In non-fasting samples, the median ICC was 0.54. ICC values were <0.50 for 71% of acylcarnitines, 48% of amino acids, 44% of biogenic amines, 36% of sphingomyelins, 34% of phosphatidylcholines and 33% of lysophosphatidylcholines. Overall, reproducibility was lower in non-fasting as compared to fasting samples, with a statistically significant difference for 19-36% of acylcarnitines, phosphatidylcholines and sphingomyelins. CONCLUSION: A single measurement per individual may be sufficient for the study of 73% and 52% of the metabolites showing ICCs >0.50 in fasting and non-fasting samples, respectively. ICCs were higher in fasting samples that are preferable to non-fasting

Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study

Chajes V., Biessy C., Ferrari P., Romieu I., Freisling H., Huybrechts I., Scalbert A., Bueno de Mesquita B., Romaguera D., Gunter M.J., Vineis P., Hansen C.P., Jakobsen M.U., Clavel-Chapelon F., Fagherazzi G., Boutron-Ruault M.C., Katzke V., Neamat-Allah J., Boeing H., Bachlechner U., Trichopoulou A., Naska A., Orfanos P., Pala V., Masala G., Mattiello A., Skeie G., Weiderpass E., Agudo A., Huerta J.M., Ardanaz E., Sanchez M.J., Dorronsoro M., Quiros J.R., Johansson I., Winkvist A., Sonested E., Key T., Khaw K.T., Wareham N.J., Peeters P.H., Slimani N.

PLoS. One; 2015; 10(2): e0118206

PMID:25675445

Abstract as provided by PubMed

BACKGROUND: Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. RESULTS: In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trend<.0001). In men, a trend was observed for doubling elaidic acid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids. CONCLUSIONS: These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids

Dietary folate intake and breast cancer risk: European prospective investigation into cancer and nutrition

de Batlle J., Ferrari P., Chajes V., Park J.Y., Slimani N., McKenzie F., Overvad K., Roswall N., Tjonneland A., Boutron-Ruault M.C., Clavel-Chapelon F., Fagherazzi G., Katzke V., Kaaks R., Bergmann M.M., Trichopoulou A., Lagiou P., Trichopoulos D., Palli D., Sieri S., Panico S., Tumino R., Vineis P., Bueno-de-Mesquita H.B., Peeters P.H., Hjartaker A., Engeset D., Weiderpass E., Sanchez S., Travier N., Sanchez M.J., Amiano P., Chirlaque M.D., Barricarte Gurrea A., Khaw K.T., Key T.J., Bradbury K.E., Ericson U., Sonestedt E., Van Guelpen B., Schneede J., Riboli E., Romieu I.

J Natl Cancer Inst; 2015; 107(1): 367

PMID:25505228

Abstract as provided by PubMed

BACKGROUND: There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided. RESULTS: A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P trend = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, P trend = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P trend = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (>12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P interaction = .035). CONCLUSIONS: Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women

Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort

Duarte-Salles T., Fedirko V., Stepien M., Aleksandrova K., Bamia C., Lagiou P., Laursen A.S., Hansen L., Overvad K., Tjonneland A., Boutron-Ruault M.C., Fagherazzi G., His M., Boeing H., Katzke V., Kuhn T., Trichopoulou A., Valanou E., Kritikou M., Masala G., Panico S., Sieri S., Ricceri F., Tumino R., Bueno-de-Mesquita H.B., Peeters P.H., Hjartaker A., Skeie G., Weiderpass E., Ardanaz E., Bonet C., Chirlaque M.D., Dorronsoro M., Quiros J.R., Johansson I., Ohlsson B., Sjoberg K., Wennberg M., Khaw K.T., Travis R.C., Wareham N., Ferrari P., Freisling H., Romieu I., Cross A.J., Gunter M., Lu Y., Jenab M.

Int J Cancer; 2015; 137(11): 2715-2728

PMID:26081477

Abstract as provided by PubMed

The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk

Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European Prospective Investigation into Cancer and Nutrition Study (EPIC)

Ekelund U., Ward H.A., Norat T., Luan J., May A.M., Weiderpass E., Sharp S.J., Overvad K., Ostergaard J.N., Tjonneland A., Johnsen N.F., Mesrine S., Fournier A., Fagherazzi G., Trichopoulou A., Lagiou P., Trichopoulos D., Li K., Kaaks R., Ferrari P., Licaj I., Jenab M., Bergmann M., Boeing H., Palli D., Sieri S., Panico S., Tumino R., Vineis P., Peeters P.H., Monnikhof E., Bueno-de-Mesquita H.B., Quiros J.R., Agudo A., Sanchez M.J., Huerta J.M., Ardanaz E., Arriola L., Hedblad B., Wirfalt E., Sund M., Johansson M., Key T.J., Travis R.C., Khaw K.T., Brage S., Wareham N.J., Riboli E.

Am J Clin Nutr; 2015; 101(3): 613-621

PMID:25733647

Abstract as provided by PubMed

BACKGROUND: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear. OBJECTIVE: We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures. DESIGN: This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m(2)) (>30), and WC (>/=102 cm for men, >/=88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures. RESULTS: Significant interactions (PA x BMI and PA x WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16-30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity. CONCLUSION: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health

Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort

Engeset D., Braaten T., Teucher B., Kuhn T., Bueno-de-Mesquita H.B., Leenders M., Agudo A., Bergmann M.M., Valanou E., Naska A., Trichopoulou A., Key T.J., Crowe F.L., Overvad K., Sonestedt E., Mattiello A., Peeters P.H., Wennberg M., Jansson J.H., Boutron-Ruault M.C., Dossus L., Dartois L., Li K., Barricarte A., Ward H., Riboli E., Agnoli C., Huerta J.M., Sanchez M.J., Tumino R., Altzibar J.M., Vineis P., Masala G., Ferrari P., Muller D.C., Johansson M., Luisa Redondo M., Tjonneland A., Olsen A., Olsen K.S., Brustad M., Skeie G., Lund E.

Eur. J Epidemiol; 2015; 30(1): 57-70

PMID:25377533

Abstract as provided by PubMed

Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992-1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99% confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p < 0.000) with fatty fish consumption and total mortality and with total fish consumption and cancer mortality (p = 0.046)

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