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  1. Perez-Cornago A, Appleby PN, Pischon T, Tsilidis KK, Tjønneland A, Olsen A, et al.
    BMC Med, 2017 07 13;15(1):115.
    PMID: 28701188 DOI: 10.1186/s12916-017-0876-7
    BACKGROUND: 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.

    METHODS: Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average of 13.9 years of follow-up, there were 7024 incident prostate cancers and 934 prostate cancer deaths.

    RESULTS: Height was not associated with total prostate cancer risk. Subgroup analyses showed heterogeneity in the association with height by tumour grade (P heterogeneity = 0.002), with a positive association with risk for high-grade but not low-intermediate-grade disease (HR for high-grade disease tallest versus shortest fifth of height, 1.54; 95% CI, 1.18-2.03). Greater height was also associated with a higher risk for prostate cancer death (HR = 1.43, 1.14-1.80). Body mass index (BMI) was significantly inversely associated with total prostate cancer, but there was evidence of heterogeneity by tumour grade (P heterogeneity = 0.01; HR = 0.89, 0.79-0.99 for low-intermediate grade and HR = 1.32, 1.01-1.72 for high-grade prostate cancer) and stage (P heterogeneity = 0.01; HR = 0.86, 0.75-0.99 for localised stage and HR = 1.11, 0.92-1.33 for advanced stage). BMI was positively associated with prostate cancer death (HR = 1.35, 1.09-1.68). The results for waist circumference were generally similar to those for BMI, but the associations were slightly stronger for high-grade (HR = 1.43, 1.07-1.92) and fatal prostate cancer (HR = 1.55, 1.23-1.96).

    CONCLUSIONS: The findings from this large prospective study show that men who are taller and who have greater adiposity have an elevated risk of high-grade prostate cancer and prostate cancer death.

  2. Obón-Santacana M, Freisling H, Peeters PH, Lujan-Barroso L, Ferrari P, Boutron-Ruault MC, et al.
    Int J Cancer, 2016 Mar 01;138(5):1129-38.
    PMID: 26376083 DOI: 10.1002/ijc.29853
    Acrylamide, classified in 1994 by IARC as "probably carcinogenic to humans," was discovered in 2002 in some heat-treated, carbohydrate-rich foods. Four prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The purpose of this nested case-control study, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, was to evaluate, for the first time, the association between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) and the risk of developing EC in non-smoking postmenopausal women. Hemoglobin adducts were measured in red blood cells by HPLC/MS/MS. Four exposure variables were evaluated: HbAA, HbGA, their sum (HbAA+HbGA), and their ratio (HbGA/HbAA). The association between hemoglobin adducts and EC was evaluated using unconditional multivariable logistic regression models, and included 383 EC cases (171 were type-I EC), and 385 controls. Exposure variables were analyzed in quintiles based on control distributions. None of the biomarker variables had an effect on overall EC (HRHbAA;Q5vsQ1 : 0.84, 95%CI: 0.49-1.48; HRHbGA;Q5vsQ1 : 0.94, 95%CI: 0.54-1.63) or type-I EC risk. Additionally, none of the subgroups investigated (BMI 
  3. Perez-Cornago A, Travis RC, Appleby PN, Tsilidis KK, Tjønneland A, Olsen A, et al.
    Int J Cancer, 2017 Jul 15;141(2):287-297.
    PMID: 28419475 DOI: 10.1002/ijc.30741
    Several dietary factors have been studied in relation to prostate cancer; however, most studies have not reported on subtypes of fruit and vegetables or tumor characteristics, and results obtained so far are inconclusive. This study aimed to examine the prospective association of total and subtypes of fruit and vegetable intake with the incidence of prostate cancer overall, by grade and stage of disease, and prostate cancer death. Lifestyle information for 142,239 men participating in the European Prospective Investigation into Cancer and Nutrition from 8 European countries was collected at baseline. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow-up time of 13.9 years, 7,036 prostate cancer cases were identified. Compared with the lowest fifth, those in the highest fifth of total fruit intake had a significantly reduced prostate cancer risk (HR = 0.91; 95% CI = 0.83-0.99; p-trend = 0.01). No associations between fruit subtypes and prostate cancer risk were observed, except for citrus fruits, where a significant trend was found (HR = 0.94; 95% CI = 0.86-1.02; p-trend = 0.01). No associations between total and subtypes of vegetables and prostate cancer risk were observed. We found no evidence of heterogeneity in these associations by tumor grade and stage, with the exception of significant heterogeneity by tumor grade (pheterogeneity <0.001) for leafy vegetables. No significant associations with prostate cancer death were observed. The main finding of this prospective study was that a higher fruit intake was associated with a small reduction in prostate cancer risk. Whether this association is causal remains unclear.
  4. Stepien M, Hughes DJ, Hybsier S, Bamia C, Tjønneland A, Overvad K, et al.
    Br J Cancer, 2017 Feb 28;116(5):688-696.
    PMID: 28152549 DOI: 10.1038/bjc.2017.1
    BACKGROUND: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers.

    METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk.

    RESULTS: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, Ptrend=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, Ptrend=0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41-15.27, Ptrend=0.0135). For IHBC and GBTC, no significant associations were observed.

    CONCLUSIONS: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.

  5. van Roekel EH, Trijsburg L, Assi N, Carayol M, Achaintre D, Murphy N, et al.
    Nutrients, 2018 May 22;10(5).
    PMID: 29789452 DOI: 10.3390/nu10050654
    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.
  6. Muller DC, Murphy N, Johansson M, Ferrari P, Tsilidis KK, Boutron-Ruault MC, et al.
    BMC Med, 2016 Jun 14;14:87.
    PMID: 27296932 DOI: 10.1186/s12916-016-0630-6
    BACKGROUND: Life expectancy is increasing in Europe, yet a substantial proportion of adults still die prematurely before the age of 70 years. We sought to estimate the joint and relative contributions of tobacco smoking, hypertension, obesity, physical inactivity, alcohol and poor diet towards risk of premature death.

    METHODS: We analysed data from 264,906 European adults from the EPIC prospective cohort study, aged between 40 and 70 years at the time of recruitment. Flexible parametric survival models were used to model risk of death conditional on risk factors, and survival functions and attributable fractions (AF) for deaths prior to age 70 years were calculated based on the fitted models.

    RESULTS: We identified 11,930 deaths which occurred before the age of 70. The AF for premature mortality for smoking was 31 % (95 % confidence interval (CI), 31-32 %) and 14 % (95 % CI, 12-16 %) for poor diet. Important contributions were also observed for overweight and obesity measured by waist-hip ratio (10 %; 95 % CI, 8-12 %) and high blood pressure (9 %; 95 % CI, 7-11 %). AFs for physical inactivity and excessive alcohol intake were 7 % and 4 %, respectively. Collectively, the AF for all six risk factors was 57 % (95 % CI, 55-59 %), being 35 % (95 % CI, 32-37 %) among never smokers and 74 % (95 % CI, 73-75 %) among current smokers.

    CONCLUSIONS: While smoking remains the predominant risk factor for premature death in Europe, poor diet, overweight and obesity, hypertension, physical inactivity, and excessive alcohol consumption also contribute substantially. Any attempt to minimise premature deaths will ultimately require all six factors to be addressed.

  7. Moskal A, Freisling H, Byrnes G, Assi N, Fahey MT, Jenab M, et al.
    Br J Cancer, 2016 Nov 22;115(11):1430-1440.
    PMID: 27764841 DOI: 10.1038/bjc.2016.334
    BACKGROUND: Much of the current literature on diet-colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

    METHODS: Among 477 312 participants, intakes of 23 nutrients were estimated from validated dietary questionnaires. Using results from a previous principal component (PC) analysis, four major nutrient patterns were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed for the association of each of the four patterns and CRC incidence using multivariate Cox proportional hazards models with adjustment for established CRC risk factors.

    RESULTS: During an average of 11 years of follow-up, 4517 incident cases of CRC were documented. A nutrient pattern characterised by high intakes of vitamins and minerals was inversely associated with CRC (HR per 1 s.d.=0.94, 95% CI: 0.92-0.98) as was a pattern characterised by total protein, riboflavin, phosphorus and calcium (HR (1 s.d.)=0.96, 95% CI: 0.93-0.99). The remaining two patterns were not significantly associated with CRC risk.

    CONCLUSIONS: Analysing nutrient patterns may improve our understanding of how groups of nutrients relate to CRC.

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