Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels in relation to zinc (copper to zinc ratio) become imbalanced in the process of CRC development. Mechanistic studies into the underlying mechanisms of regulation and action are required to further examine a possible role for higher copper and copper/zinc ratio levels in CRC development and progression.
Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most have been of insufficient size to identify heterogeneous associations with precision.
Little is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer.
The relationship between body size and prostate cancer risk, and in particular risk by tumour characteristics, is not clear because most studies have not differentiated between high-grade or advanced stage tumours, but rather have assessed risk with a combined category of aggressive disease. We investigated the association of height and adiposity with incidence of and death from prostate cancer in 141,896 men in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
Metabolomics is now widely used to characterize metabolic phenotypes associated with lifestyle risk factors such as obesity. The objective of the present study was to explore the associations of body mass index (BMI) with 145 metabolites measured in blood samples in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolites were measured in blood from 392 men from the Oxford (UK) cohort (EPIC-Oxford) and in 327 control subjects who were part of a nested case-control study on hepatobiliary carcinomas (EPIC-Hepatobiliary). Measured metabolites included amino acids, acylcarnitines, hexoses, biogenic amines, phosphatidylcholines, and sphingomyelins. Linear regression models controlled for potential confounders and multiple testing were run to evaluate the associations of metabolite concentrations with BMI. 40 and 45 individual metabolites showed significant differences according to BMI variations, in the EPIC-Oxford and EPIC-Hepatobiliary subcohorts, respectively. Twenty two individual metabolites (kynurenine, one sphingomyelin, glutamate and 19 phosphatidylcholines) were associated with BMI in both subcohorts. The present findings provide additional knowledge on blood metabolic signatures of BMI in European adults, which may help identify mechanisms mediating the relationship of BMI with obesity-related diseases.
Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions.
Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations.
Wood, Angela M; Kaptoge, Stephen; Butterworth, Adam S; Willeit, Peter; Warnakula, Samantha; Bolton, Thomas; Paige, Ellie; Paul, Dirk S; Sweeting, Michael; Burgess, Stephen; Bell, Steven; Astle, William; Stevens, David; Koulman, Albert; Selmer, Randi M; Verschuren, W M Monique; Sato, Shinichi; Njølstad, Inger; Woodward, Mark; Salomaa, Veikko; Nordestgaard, Børge G; Yeap, Bu B; Fletcher, Astrid; Melander, Olle; Kuller, Lewis H; Balkau, Beverley; Marmot, Michael; Koenig, Wolfgang; Casiglia, Edoardo; Cooper, Cyrus; Arndt, Volker; Franco, Oscar H; Wennberg, Patrik; Gallacher, John; de la Cámara, Agustín Gómez; Völzke, Henry; Dahm, Christina C; Dale, Caroline E; Bergmann, Manuela M; Crespo, Carlos J; van der Schouw, Yvonne T; Kaaks, Rudolf; Simons, Leon A; Lagiou, Pagona; Schoufour, Josje D; Boer, Jolanda M A; Key, Timothy J; Rodriguez, Beatriz; Moreno-Iribas, Conchi; Davidson, Karina W; Taylor, James O; Sacerdote, Carlotta; Wallace, Robert B; Quiros, J Ramon; Tumino, Rosario; Blazer, Dan G; Linneberg, Allan; Daimon, Makoto; Panico, Salvatore; Howard, Barbara; Skeie, Guri; Strandberg, Timo; Weiderpass, Elisabete; Nietert, Paul J; Psaty, Bruce M; Kromhout, Daan; Salamanca-Fernandez, Elena; Kiechl, Stefan; Krumholz, Harlan M; Grioni, Sara; Palli, Domenico; Huerta, José M; Price, Jackie; Sundström, Johan; Arriola, Larraitz; Arima, Hisatomi; Travis, Ruth C; Panagiotakos, Demosthenes B; Karakatsani, Anna; Trichopoulou, Antonia; Kühn, Tilman; Grobbee, Diederick E; Barrett-Connor, Elizabeth; van Schoor, Natasja; Boeing, Heiner; Overvad, Kim; Kauhanen, Jussi; Wareham, Nick; Langenberg, Claudia; Forouhi, Nita; Wennberg, Maria; Després, Jean-Pierre; Cushman, Mary; Cooper, Jackie A; Rodriguez, Carlos J; Sakurai, Masaru; Shaw, Jonathan E; Knuiman, Matthew; Voortman, Trudy; Meisinger, Christa; Tjønneland, Anne; Brenner, Hermann; Palmieri, Luigi; Dallongeville, Jean; Brunner, Eric J; Assmann, Gerd; Trevisan, Maurizio; Gillum, Richard F; Ford, Ian; Sattar, Naveed; Lazo, Mariana; Thompson, Simon G; Ferrari, Pietro; Leon, David A; Smith, George Davey; Peto, Richard; Jackson, Rod; Banks, Emily; Di Angelantonio, Emanuele; Danesh, John(2018)
Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.
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