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Search Result (493 REFERENCES)

2015

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 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

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.

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

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

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

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

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
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

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)

A prospective study of one-carbon metabolism biomarkers and cancer of the head and neck and esophagus

Fanidi A., Relton C., Ueland P.M., Midttun O., Vollset S.E., Travis R.C., Trichopoulou A., Lagiou P., Trichopoulos D., Bueno-de-Mesquita H.B., Ros M., Boeing H., Tumino R., Panico S., Palli D., Sieri S., Vineis P., Sanchez M.J., Huerta J.M., Barricarte Gurrea A., Lujan-Barroso L., Quiros J.R., Tjonneland A., Halkjaer J., Boutron-Ruault M.C., Clavel-Chapelon F., Cadeau C., Weiderpass E., Johansson M., Riboli E., Brennan P., Johansson M.

Int J Cancer; 2015; 136(4): 915-927

PMID:24975698

Abstract as provided by PubMed

Experimental and epidemiological data suggest that factors of one-carbon metabolism are important in the pathogenesis of several cancers, but prospective data on head and neck cancer (HNC) and esophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants from 10 countries who donated a blood sample. The current study included 516 cancer cases of the head and neck and esophagus and 516 individually matched controls. Plasma levels of vitamins B2, B6, B9 (folate), B12, and methionine and homocysteine were measured in pre-diagnostic plasma samples and analyzed in relation to HNC and esophagus cancer risk, as well as post-diagnosis all-cause mortality. After controlling for risk factors, study participants with higher levels of homocysteine had elevated risk of HNC, the odds ratio (OR) in conditional analysis when comparing the top and bottom quartiles of homocysteine [ORQ4 vs. Q1 ] being 2.13 (95% confidence interval [95% CI] 1.13-4.00, p for trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (ORQ4 vs. Q1 0.63, 95% CI 0.35-1.16, p for trend 0.02). Subgroup analyses by anatomical sub-site indicated particularly strong associations with circulating homocysteine for oral cavity and gum cancer (p for trend 8 x 10(-4) ), as well as for oropharynx cancer (p for trend 0.008). Plasma concentrations of the other investigated biomarkers did not display any clear association with risk or survival. In conclusion, study participants with elevated circulating levels of homocysteine had increased risk of developing squamous cell carcinoma of the head and neck

Body iron status and gastric cancer risk in the EURGAST study

Fonseca-Nunes A., Agudo A., Aranda N., Arija V., Cross A. J., Molina E., Sanchez M. J., Bueno-de-Mesquita H. B., Siersema P., Weiderpass E., Krogh V., Mattiello A., Tumino R., Saieva C., Naccarati A., Ohlsson B., Sjoberg K., Boutron-Ruault M. C., Cadeau C., Fagherazzi G., Boeing H., Steffen A., Kuhn T., Katzke V., Tjonneland A., Olsen A., Khaw K. T., Wareham N., Key T., Lu Y., Riboli E., Peeters P. H., Gavrila D., Dorronsoro M., Quiros J. R., Barricarte A., Jenab M., Zamora-Ros R., Freisling H., Trichopoulou A., Lagiou P., Bamia C., Jakszyn P.

Int J Cancer; 2015; 137(12): 2904-14

PMID:26135329

Abstract as provided by PubMed

Although it appears biologically plausible for iron to be associated with gastric carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body iron status and gastric cancer risk, we conducted a nested case-control study in the multicentric European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured prediagnostic serum iron, ferritin, transferrin and C-reactive protein, and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by iron metrics were estimated from multivariable conditional logistic regression models. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2 = 0.80, 95% CI = 0.72-0.88; OR10%increment = 0.87, 95% CI = 0.78-0.97, respectively). These associations appear to be restricted to noncardia gastric cancer (ferritin showed a p for heterogeneity = 0.04 and TS had a p for heterogeneity = 0.02), and no differences were found by histological type. TIBC increased risk of overall gastric cancer (OR50 microg/dl = 1.13, 95% CI = 1.02-1.2) and also with noncardia gastric cancer (p for heterogeneity = 0.04). Additional analysis suggests that time between blood draw and gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of gastric cancer related to higher body iron stores as measured by serum iron and ferritin. Further investigation is needed to clarify the role of iron in gastric carcinogenesis.

Reproductive and hormone-related risk factors for epithelial ovarian cancer by histologic pathways, invasiveness and histologic subtypes: Results from the EPIC cohort

Fortner R. T., Ose J., Merritt M. A., Schock H., Tjonneland A., Hansen L., Overvad K., Dossus L., Clavel-Chapelon F., Baglietto L., Boeing H., Trichopoulou A., Benetou V., Lagiou P., Agnoli C., Mattiello A., Masala G., Tumino R., Sacerdote C., Bueno-de-Mesquita H. B., Onland-Moret N. C., Peeters P. H., Weiderpass E., Torhild Gram I., Duell E. J., Larranaga N., Ardanaz E., Sanchez M. J., Chirlaque M. D., Brandstedt J., Idahl A., Lundin E., Khaw K. T., Wareham N., Travis R. C., Rinaldi S., Romieu I., Gunter M. J., Riboli E., Kaaks R.

Int J Cancer; 2015; 137(5): 1196-208

PMID:25656413

Abstract as provided by PubMed

Whether risk factors for epithelial ovarian cancer (EOC) differ by subtype (i.e., dualistic pathway of carcinogenesis, histologic subtype) is not well understood; however, data to date suggest risk factor differences. We examined associations between reproductive and hormone-related risk factors for EOC by subtype in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 334,126 women with data on reproductive and hormone-related risk factors (follow-up: 1992-2010), 1,245 incident cases of EOC with known histology and invasiveness were identified. Data on tumor histology, grade, and invasiveness, were available from cancer registries and pathology record review. We observed significant heterogeneity by the dualistic model (i.e., type I [low grade serous or endometrioid, mucinous, clear cell, malignant Brenner] vs. type II [high grade serous or endometrioid]) for full-term pregnancy (phet = 0.02). Full-term pregnancy was more strongly inversely associated with type I than type II tumors (ever vs. never: type I: relative risk (RR) 0.47 [95% confidence interval (CI): 0.33-0.69]; type II, RR: 0.81 [0.61-1.06]). We observed no significant differences in risk in analyses by major histologic subtypes of invasive EOC (serous, mucinous, endometrioid, clear cell). None of the investigated factors were associated with borderline tumors. Established protective factors, including duration of oral contraceptive use and full term pregnancy, were consistently inversely associated with risk across histologic subtypes (e.g., ever full-term pregnancy: serous, RR: 0.73 [0.58-0.92]; mucinous, RR: 0.53 [0.30-0.95]; endometrioid, RR: 0.65 [0.40-1.06]; clear cell, RR: 0.34 [0.18-0.64]; phet = 0.16). These results suggest limited heterogeneity between reproductive and hormone-related risk factors and EOC subtypes.

Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort

Hughes D.J., Fedirko V., Jenab M., Schomburg L., Meplan C., Freisling H., Bueno-de-Mesquita H.B., Hybsier S., Becker N.P., Czuban M., Tjonneland A., Outzen M., Boutron-Ruault M.C., Racine A., Bastide N., Kuhn T., Kaaks R., Trichopoulos D., Trichopoulou A., Lagiou P., Panico S., Peeters P.H., Weiderpass E., Skeie G., Dagrun E., Chirlaque M.D., Sanchez M.J., Ardanaz E., Ljuslinder I., Wennberg M., Bradbury K.E., Vineis P., Naccarati A., Palli D., Boeing H., Overvad K., Dorronsoro M., Jakszyn P., Cross A.J., Quiros J.R., Stepien M., Kong S.Y., Duarte-Salles T., Riboli E., Hesketh J.E.

Int J Cancer; 2015; 136(5): 1149-1161

Abstract as provided by PubMed

Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case-control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X-ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 mug/L and 4.3 mg/L in cases and 85.6 mug/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non-significant lower CRC risk (IRR = 0.92, 95% CI: 0.82-1.03 per 25 mug/L increase). However, sub-group analyses by sex showed a statistically significant association for women (ptrend = 0.032; per 25 mug/L Se increase, IRR = 0.83, 95% CI: 0.70-0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (ptrend = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82-0.98) with the association more apparent in women (ptrend = 0.004; IRR = 0.82, 95% CI: 0.72-0.94 per 0.806 mg/L increase) than men (ptrend = 0.485; IRR = 0.98, 95% CI: 0.86-1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women

Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: a nested case-control study: plasma micronutrients and pancreatic cancer risk

Jeurnink S.M., Ros M.M., Leenders M., van Duijnhoven F.J., Siersema P.D., Jansen E.H., Van Gils C.H., Bakker M.F., Overvad K., Roswall N., Tjonneland A., Boutron-Ruault M.C., Racine A., Cadeau C., Grote V., Kaaks R., Aleksandrova K., Boeing H., Trichopoulou A., Benetou V., Valanou E., Palli D., Krogh V., Vineis P., Tumino R., Mattiello A., Weiderpass E., Skeie G., Castano J.M., Duell E.J., Barricarte A., Molina-Montes E., Arguelles M., Dorronsoro M., Johansen D., Lindkvist B., Sund M., Crowe F.L., Khaw K.T., Jenab M., Fedirko V., Riboli E., Bueno-de-Mesquita H.B.

Int. J Cancer; 2015; 136(6): E665-E676

Abstract as provided by PubMed

Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (alpha- and beta-carotene, lycopene, beta-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), alpha- and gamma-tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma beta-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend = 0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend = 0.06) and alpha-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend = 0.08. For alpha- and beta-carotene, lutein, sum of carotenoids and gamma-tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of beta-carotene, zeaxanthin and alpha-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted

Lag times between lymphoproliferative disorder and clinical diagnosis of chronic lymphocytic leukemia: a prospective analysis using plasma soluble CD23

Kaaks R., Sookthai D., Luczynska A., Oakes C.C., Becker S., Johnson T., Johansson A., Melin B., Sjoberg K., Trichopoulos D., Trichopoulou A., Lagiou P., Mattiello A., Tumino R., Masala G., Agnoli C., Boeing H., Aleksandrova K., Brennan P., Franceschi S., Roulland S., Casabonne D., de Sanjose S., Sanchez M.J., Huerta J.M., Ardanaz E., Sala N., Overvad K., Tjonneland A., Halkjaer J., Weiderpass E., Bueno-de-Mesquita H.B., Vermeulen R., Peeters P.H., Vineis P., Kelly R.S., Khaw K.T., Travis R.C., Key T.J., Riboli E., Nieters A.

Cancer Epidemiol. Biomarkers Prev; 2015; 24(3): 538-545

PMID:25542829

Abstract as provided by PubMed

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a chronic disease that often progresses slowly from a precursor stage, monoclonal B-cell lymphocytosis (MBL), and that can remain undiagnosed for a long time. METHODS: Within the European Prospective Investigation into Cancer cohort, we measured prediagnostic plasma sCD23 for 179 individuals who eventually were diagnosed with CLL and an equal number of matched control subjects who remained free of cancer. RESULTS: In a very large proportion of CLL patients' plasma sCD23 was clearly elevated 7 or more years before diagnosis. Considering sCD23 as a disease predictor, the area under the ROC curve (AUROC) was 0.95 [95% confidence interval (CI), 0.90-1.00] for CLL diagnosed within 0.1 to 2.7 years after blood measurement, 0.90 (95% CI, 0.86-0.95) for diagnosis within 2.8 to 7.3 years, and 0.76 (95% CI, 0.65-0.86) for CLL diagnosed between 7.4 and 12.5 years. Even at a 7.4-year and longer time interval, elevated plasma sCD23 could predict a later clinical diagnosis of CLL with 100% specificity at >45% sensitivity. CONCLUSIONS: Our findings provide unique documentation for the very long latency times during which measurable B-cell lymphoproliferative disorder exists before the clinical manifestation of CLL. IMPACT: Our findings have relevance for the interpretation of prospective epidemiologic studies on the causes of CLL in terms of reverse causation bias. The lag times indicate a time frame within which an early detection of CLL would be theoretically possible. Cancer Epidemiol Biomarkers Prev; 24(3); 538-45. (c)2014 AACR

Determinants of the t(14;18) translocation and their role in t(14;18)-positive follicular lymphoma

Kelly R. S., Roulland S., Morgado E., Sungalee S., Jouve N., Tumino R., Krogh V., Panico S., Polidoro S., Masala G., Sanchez M. J., Chirlaque M. D., Sala N., Gurrea A. B., Dorronsoro M., Travis R. C., Riboli E., Gunter M., Murphy N., Vermeulen R., Bueno-de-Mesquita H. B., Peeters P. H., Trichopoulou A., Trichopoulos D., Lagiou P., Nieters A., Canzian F., Kaaks R., Boeing H., Weiderpass E., Stocks T., Melin B., Overvad K., Tjonneland A., Olsen A., Brennan P., Johansson M., Nadel B., Vineis P.

Cancer Causes Control; 2015; 26(12): 1845-55

PMID:26424368

Abstract as provided by PubMed

PURPOSE: The strong association between t(14;18) translocation and follicular lymphoma (FL) is well known. However, the determinants of this chromosomal aberration and their role in t(14;18) associated FL remain to be established. METHODS: t(14;18) frequency within the B cell lymphoma 2 major breakpoint region was determined for 135 incident FL cases and 251 healthy controls as part of a nested case-control study within the European Prospective Investigation into Cancer cohort. Quantitative real-time PCR was performed in DNA extracted from blood samples taken at recruitment. The relationship between prevalence and frequency of the translocation with baseline anthropometric, lifestyle, and dietary factors in cases and controls was determined. Unconditional logistic regression was used to explore whether the risk of FL associated with these factors differed in t(14;18)(+) as compared to t(14;18)(-) cases. RESULTS: Among incident FL cases, educational level (chi (2) p = 0.021) and height (chi (2) p = 0.025) were positively associated with t(14;18) prevalence, and cases with high frequencies [t(14;18)(HF)] were significantly taller (t test p value = 0.006). These findings were not replicated in the control population, although there were a number of significant associations with dietary variables. Further analyses revealed that height was a significant risk factor for t(14;18)(+) FL [OR 6.31 (95 % CI 2.11, 18.9) in the tallest versus the shortest quartile], but not t(14;18)(-) cases. CONCLUSIONS: These findings suggest a potential role for lifestyle factors in the prevalence and frequency of the t(14;18) translocation. The observation that the etiology of FL may differ by t(14;18) status, particularly with regard to height, supports the subdivision of FL by translocation status.

Human papillomavirus antibodies and future risk of anogenital cancer: a nested case-control study in the European prospective investigation into cancer and nutrition study

Kreimer A.R., Brennan P., Lang Kuhs K.A., Waterboer T., Clifford G., Franceschi S., Michel A., Willhauck-Fleckenstein M., Riboli E., Castellsague X., Hildesheim A., Fortner R.T., Kaaks R., Palli D., Ljuslinder I., Panico S., Clavel-Chapelon F., Boutron-Ruault M.C., Mesrine S., Trichopoulou A., Lagiou P., Trichopoulos D., Peeters P.H., Cross A.J., Bueno-de-Mesquita H.B., Vineis P., Larranaga N., Pala V., Sanchez M.J., Navarro C., Barricarte A., Tumino R., Khaw K.T., Wareham N., Boeing H., Steffen A., Travis R.C., Quiros J.R., Weiderpass E., Pawlita M., Johansson M.

J Clin. Oncol; 2015; 33(8): 877-884

PMID:25667279

Abstract as provided by PubMed

PURPOSE: Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. METHODS: Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. RESULTS: HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non-type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis. CONCLUSION: HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers

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