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  1. Allen NE, Travis RC, Appleby PN, Albanes D, Barnett MJ, Black A, et al.
    J Natl Cancer Inst, 2016 11;108(11).
    PMID: 27385803 DOI: 10.1093/jnci/djw153
    BACKGROUND: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade.

    METHODS: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided.

    RESULTS: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, Pheterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, Ptrend < .001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, Pheterogeneity = .08).

    CONCLUSIONS: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.

  2. Obón-Santacana M, Luján-Barroso L, Freisling H, Naudin S, Boutron-Ruault MC, Mancini FR, et al.
    Int J Cancer, 2020 Jan 01;146(1):76-84.
    PMID: 31107546 DOI: 10.1002/ijc.32415
    Four epidemiologic studies have assessed the association between nut intake and pancreatic cancer risk with contradictory results. The present study aims to investigate the relation between nut intake (including seeds) and pancreatic ductal adenocarcinoma (PDAC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to estimate hazards ratio (HR) and 95% confidence intervals (95% CI) for nut intake and PDAC risk. Information on intake of nuts was obtained from the EPIC country-specific dietary questionnaires. After a mean follow-up of 14 years, 476,160 participants were eligible for the present study and included 1,283 PDAC cases. No association was observed between consumption of nuts and PDAC risk (highest intake vs nonconsumers: HR, 0.89; 95% CI, 0.72-1.10; p-trend = 0.70). Furthermore, no evidence for effect-measure modification was observed when different subgroups were analyzed. Overall, in EPIC, the highest intake of nuts was not statistically significantly associated with PDAC risk.
  3. Zamora-Ros R, Cayssials V, Jenab M, Rothwell JA, Fedirko V, Aleksandrova K, et al.
    Eur J Epidemiol, 2018 Nov;33(11):1063-1075.
    PMID: 29761424 DOI: 10.1007/s10654-018-0408-6
    Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HRlog2 = 1.06, 95% CI 0.99-1.14) or in men (HRlog2 = 0.97, 95% CI 0.90-1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HRlog2 = 0.91, 95% CI 0.85-0.97) and positively associated with rectal cancer in women (HRlog2 = 1.10, 95% CI 1.02-1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.
  4. Agudo A, Cayssials V, Bonet C, Tjønneland A, Overvad K, Boutron-Ruault MC, et al.
    Am J Clin Nutr, 2018 Apr 01;107(4):607-616.
    PMID: 29635497 DOI: 10.1093/ajcn/nqy002
    BACKGROUND: Chronic inflammation plays a critical role in the pathogenesis of the 2 major types of gastric cancer. Several foods, nutrients, and nonnutrient food components seem to be involved in the regulation of chronic inflammation.

    OBJECTIVE: We assessed the association between the inflammatory potential of the diet and the risk of gastric carcinoma, overall and for the 2 major subsites: cardia cancers and noncardia cancers.

    DESIGN: A total of 476,160 subjects (30% men, 70% women) from the European Investigation into Cancer and Nutrition (EPIC) study were followed for 14 y, during which 913 incident cases of gastric carcinoma were identified, including 236 located in the cardia, 341 in the distal part of the stomach (noncardia), and 336 with overlapping or unknown tumor site. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated with the use of 28 dietary components and their corresponding inflammatory scores. The association between the ISD and gastric cancer risk was estimated by HRs and 95% CIs calculated by multivariate Cox regression models adjusted for confounders.

    RESULTS: The inflammatory potential of the diet was associated with an increased risk of gastric cancer. The HR (95% CI) for each increase in 1 SD of the ISD were 1.25 (1.12, 1.39) for all gastric cancers, 1.30 (1.06, 1.59) for cardia cancers, and 1.07 (0.89, 1.28) for noncardia cancers. The corresponding values for the highest compared with the lowest quartiles of the ISD were 1.66 (1.26, 2.20), 1.94 (1.14, 3.30), and 1.07 (0.70, 1.70), respectively.

    CONCLUSIONS: Our results suggest that low-grade chronic inflammation induced by the diet may be associated with gastric cancer risk. This pattern seems to be more consistent for gastric carcinomas located in the cardia than for those located in the distal stomach. This study is listed on the ISRCTN registry as ISRCTN12136108.

  5. Zamora-Ros R, Cayssials V, Franceschi S, Kyrø C, Weiderpass E, Hennings J, et al.
    Int J Cancer, 2020 Apr 01;146(7):1841-1850.
    PMID: 31342519 DOI: 10.1002/ijc.32589
    Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77-1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80-1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55-2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.
  6. 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.
  7. 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.

  8. Harms LM, Scalbert A, Zamora-Ros R, Rinaldi S, Jenab M, Murphy N, et al.
    Br J Nutr, 2020 Jan 28;123(2):198-208.
    PMID: 31583990 DOI: 10.1017/S0007114519002538
    Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterise the association between plasma concentrations of thirty-five polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis, the OR and 95 % CI of elevated serum hsCRP (>3 mg/l) were calculated within quartiles and per standard deviation higher level of plasma polyphenol concentrations. In a multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per standard deviation) was associated with 29 (95 % CI 50, 1) % lower odds of elevated hsCRP. In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR 0·66, 95 % CI 0·46, 0·96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR 0·58, 95 % CI 0·39, 0·86), 3,4-dihydroxyphenylpropionic acid (OR 0·63, 95 % CI 0·46, 0·87), ferulic acid (OR 0·65, 95 % CI 0·44, 0·96) and caffeic acid (OR 0·69, 95 % CI 0·51, 0·93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR 0·67, 95 % CI 0·48, 0·93). The present study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies.
  9. Aglago EK, Huybrechts I, Murphy N, Casagrande C, Nicolas G, Pischon T, et al.
    Clin Gastroenterol Hepatol, 2020 Mar;18(3):654-666.e6.
    PMID: 31252190 DOI: 10.1016/j.cgh.2019.06.031
    BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs.

    RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026).

    CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

  10. Heath AK, Muller DC, van den Brandt PA, Papadimitriou N, Critselis E, Gunter M, et al.
    Breast Cancer Res, 2020 01 13;22(1):5.
    PMID: 31931881 DOI: 10.1186/s13058-019-1244-7
    BACKGROUND: Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study.

    METHODS: Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS).

    RESULTS: Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS.

    CONCLUSIONS: Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.

  11. Kyrø C, Zamora-Ros R, Scalbert A, Tjønneland A, Dossus L, Johansen C, et al.
    Breast Cancer Res Treat, 2015 Nov;154(2):389-401.
    PMID: 26531755 DOI: 10.1007/s10549-015-3595-9
    The aim was to investigate the association between pre-diagnostic intakes of polyphenol classes (flavonoids, lignans, phenolic acids, stilbenes, and other polyphenols) in relation to breast cancer survival (all-cause and breast cancer-specific mortality). We used data from the European Prospective Investigation into Cancer and Nutrition cohort. Pre-diagnostic usual diet was assessed using dietary questionnaires, and polyphenol intakes were estimated using the Phenol-Explorer database. We followed 11,782 breast cancer cases from time of diagnosis until death, end of follow-up or last day of contact. During a median of 6 years, 1482 women died (753 of breast cancer). We related polyphenol intake to all-cause and breast cancer-specific mortality using Cox proportional hazard models with time since diagnosis as underlying time and strata for age and country. Among postmenopausal women, an intake of lignans in the highest versus lowest quartile was related to a 28 % lower risk of dying from breast (adjusted model: HR, quartile 4 vs. quartile 1, 0.72, 95 % CI 0.53; 0.98). In contrast, in premenopausal women, a positive association between lignan intake and all-cause mortality was found (adjusted model: HR, quartile 4 vs. quartile 1, 1.63, 95 % CI 1.03; 2.57). We found no association for other polyphenol classes. Intake of lignans before breast cancer diagnosis may be related to improved survival among postmenopausal women, but may on the contrary worsen the survival for premenopausal women. This suggests that the role of phytoestrogens in breast cancer survival is complex and may be dependent of menopausal status.
  12. Zamora-Ros R, Alghamdi MA, Cayssials V, Franceschi S, Almquist M, Hennings J, et al.
    Eur J Nutr, 2019 Dec;58(8):3303-3312.
    PMID: 30535794 DOI: 10.1007/s00394-018-1874-z
    PURPOSE: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study.

    METHODS: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires.

    RESULTS: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97-1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95-1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95-1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81-0.99), but this association was based on a sub-analysis with a small number of cancer cases.

    CONCLUSIONS: In this large prospective study, coffee and tea consumptions were not associated with TC risk.

  13. van Duijnhoven FJB, Jenab M, Hveem K, Siersema PD, Fedirko V, Duell EJ, et al.
    Int J Cancer, 2018 Mar 15;142(6):1189-1201.
    PMID: 29114875 DOI: 10.1002/ijc.31146
    Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow-up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.
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