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.
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.
For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, P
=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, P
=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, P
=0.0135). For IHBC and GBTC, no significant associations were observed.
Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Citrus intake has been suggested to increase the risk of skin cancer. Although this relation is highly plausible biologically, epidemiologic evidence is lacking. We aimed to examine the potential ...association between citrus intake and skin cancer risk. EPIC is an ongoing multi-center prospective cohort initiated in 1992 and involving ~ 520,000 participants who have been followed-up in 23 centers from 10 European countries. Dietary data were collected at baseline using validated country-specific dietary questionnaires. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up of 13.7 years, 8448 skin cancer cases were identified among 270,112 participants. We observed a positive linear dose–response relationship between total citrus intake and skin cancer risk (HR = 1.10, 95% CI 1.03–1.18 in the highest vs. lowest quartile; P
trend
= 0.001), particularly with basal cell carcinoma (BCC) (HR = 1.11, 95% CI 1.02–1.20, P
trend
= 0.007) and squamous cell carcinoma (SCC) (HR = 1.23, 95% CI 1.04–1.47, P
trend
= 0.01). Citrus fruit intake was positively associated with skin cancer risk (HR = 1.08, 95% CI 1.01–1.16, P
trend
= 0.01), particularly with melanoma (HR = 1.23, 95% CI 1.02–1.48; P
trend
= 0.01), although with no heterogeneity across skin cancer types (P
homogeneity
= 0.21). Citrus juice was positively associated with skin cancer risk (P
trend
= 0.004), particularly with BCC (P
trend
= 0.008) and SCC (P
trend
= 0.004), but not with melanoma (P
homogeneity
= 0.02). Our study suggests moderate positive linear dose–response relationships between citrus intake and skin cancer risk. Studies with available biomarker data and the ability to examine sun exposure behaviors are warranted to clarify these associations and examine the phototoxicity mechanisms of furocoumarin-rich foods.
Recent evidence suggest that energy distribution during the daytimecould be a potential determinant for the development of metabolic syndrome (MetS).
To cross-sectionally assess the association ...between breakfast size and the prevalence of MetS in Spanish adults.
Our study included a subset of 3644 participants from the European Prospective Investigation into Cancer and Nutrition Spain study recontacted between 2017-2018. Information on diet, sociodemographic, lifestyle, sleep quality, and chronotype was collected using standardized questionnaires, while anthropometric and blood pressure data were measured in a face-to-face personal interview by a nurse. MetS was defined according to the Adult Treatment Panel III (ATPIII) definition by measuring serum levels of total cholesterol, tryglycerides and glucose. Breakfast size was calculated as: (energy from breakfast/total energy intake) * 2000 kcal. To evaluate the association between breakfast size and MetS prevalence, a multivariable logistic regression model adjusted by potential confounders was used to estimate OR and 95% CI.
Prevalence of MetS in our study was 40.7%. The mean breakfast size was 306.6 * 2000 kcal (15% of the total daily energy intake), with 14 (0.4%) participants skipping breakfast. Participants in the highest quartile of breakfast size had a lower MetS prevalence compared to participants in the lowest quartile (OR
= 0.62; 95% CI = 0.51-0.76;
-trend < 0.001). No modification of the estimated ORs by sex, breakfast time, and number of eating occasions per day were observed.
Our results suggest that higher breakfast size is associated with lower prevalence of MetS in Spanish adults, supporting the importance of a high energy breakfast. Further prospective studies are necessary to confirm these findings.
Existing epidemiological evidence regarding the potential role of (poly)phenol intake in prostate cancer (PCa) risk is scarce and, in the case of flavonoids, it has been suggested that their intake ...may increase PCa risk. We investigated the associations between the intake of the total and individual classes and subclasses of (poly)phenols and the risk of PCa, including clinically relevant subtypes. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort included 131,425 adult men from seven European countries. (Poly)phenol intake at baseline was assessed by combining validated center/country-specific dietary questionnaires and the Phenol-Explorer database. Multivariable-adjusted Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). In total, 6939 incident PCa cases (including 3501 low-grade and 710 high-grade, 2446 localized and 1268 advanced, and 914 fatal Pca cases) were identified during a mean follow-up of 14 years. No associations were observed between the total intake of (poly)phenols and the risk of PCa, either overall (HR
= 0.99, 95% CI 0.94-1.04) or according to PCa subtype. Null associations were also found between all classes (phenolic acids, flavonoids, lignans, and stilbenes) and subclasses of (poly)phenol intake and the risk of PCa, overall and according to PCa subtype. The results of the current large prospective cohort study do not support any association between (poly)phenol intake and PCa incidence.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The specific association of olive oil consumption with coronary heart disease (CHD) or stroke has not been totally established.
Objective: to examine whether olive oil consumption is associated with ...subclinical atherosclerosis, the risk of total cardiovascular disease (CVD), CHD, and stroke.
Three cohorts were included: AWHS (2318 men), SUN Project (18,266 men and women), and EPIC-Spain (39,393 men and women). Olive oil consumption was measured at baseline using validated questionnaires.
In the AWHS, 747 participants had a positive coronary artery calcium score (CACS>0), and the OR (95% CI) was 0.89 (0.72, 1.10) in those with virgin olive oil consumption ≥30 g/day (v. <10 g/day). In the SUN Project (follow-up 10.8 years) 261 total CVD cases occurred, and the HR was 0.57 (0.34, 0.96) for consumptions ≥30 g/day (v. <10 g/day). In the EPIC-Spain (follow-up 22.8 years) 1300 CHD cases and 938 stroke cases occurred; the HRs for stroke according, 0 to <10 (ref), 10 to <20, 20 to <30, and ≥30 g/day of olive oil consumption, were 0.84 (0.70, 1.02), 0.80 (0.66, 0.96), 0.89 (0.74, 1.07). A weaker association was observed for CHD. The association was stronger among those consuming virgin olive oil, instead of common (refined).
Olive oil is associated with lower risk of CVD and stroke. The maximum benefit could be obtained with a consumption between 20 and 30 g/day. The association could be stronger for virgin olive oil and might operate from the early stages of the disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Polyphenols are bioactive compounds from plants with antioxidant properties that may have a protective role against body weight gain, with adipose tissue and systemic oxidative stress as potential ...targets. We aimed to investigate the dietary intake of individual polyphenols and their association with 5-year body weight change in a sub-cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). This study included 349,165 adult participants from nine European countries. Polyphenol intake was estimated through country-specific validated dietary questionnaires and the Phenol-Explorer database. Body weight was obtained at recruitment and after a mean follow-up time of 5 years. Associations were estimated using multilevel mixed linear regression models. From 91 polyphenols included, the majority (n = 67) were inversely associated with 5-year body weight change after FDR-correction (q < 0.05). The greatest inverse associations were observed for quercetin 3-O-rhamnoside (change in weight for doubling in intake: −0.071 (95% CI: −0.085; −0.056) kg/5 years). Only 13 polyphenols showed positive associations with body weight gain, mainly from the subclass hydroxycinnamic acids (HCAs) with coffee as the main dietary source, such as 4-caffeoylquinic acid (0.029 (95% CI: 0.021; 0.038) kg/5 years). Individual polyphenols with fruit, tea, cocoa and whole grain cereals as the main dietary sources may contribute to body weight maintenance in adults. Individual HCAs may have different roles in body weight change depending on their dietary source.
The Mediterranean diet (MD) has been proposed as a healthy diet with a potential to lower the incidence of several types of cancer, but there is no data regarding thyroid cancer (TC). We investigated ...the association between MD adherence, and its components, and the differentiated TC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
Over 450,000 men and women from nine European countries were followed up for a mean of 14.1 years, during which 712 differentiated TC cases were identified. Adherence to MD was estimated using the relative MD (rMED) score, an 18-point scale including alcohol, and the adapted rMED (arMED) score, a 16-point scale excluding alcohol. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounding factors.
Adherence to the arMED score was not associated with the risk of differentiated TC (HR
= 0.94, 95% CI: 0.70-1.25;
-trend 0.27), while a suggestive, but non-statistically significant inverse relationship was observed with rMED (HR
= 0.88, 95% CI: 0.68-1.14;
-trend 0.17). Low meat (HR
= 0.81, 95% CI: 0.67-0.99;
-trend = 0.04) and moderate alcohol (HR
= 0.88, 95% CI: 0.75-1.03) intake were related with lower differentiated TC risk.
Our study shows that a high adherence to MD is not strongly related to differentiated TC risk, although further research is required to confirm the impact of MD and, especially, meat intake in TC risk.
Although total plasma homocysteine (tHcy) has been extensively studied as a risk factor of CVD, longitudinal evidence on its association with mortality is scarce, especially among the elderly. The ...study cohort consisted of 215 subjects (eighty-eight male and 127 female), aged 60 years or older, recruited in fourteen elderly care institutions from Asturias (Spain). All participants were free of major chronic pathology and took no vitamin and/or mineral supplements. Baseline determinations included tHcy in plasma and folate, vitamin B12 and Se in serum. Survival analyses were performed by quintiles of these factors after 6 years (mean follow-up time 4·3 years) by means of Cox regression models. During follow-up time sixty participants died. tHcy above 16·7 μmol/l was associated with an increased risk of mortality in the sample (relative risk 2·30 (95 % CI 1·02, 5·17)). Among the nutritional determinants of tHcy evaluated, folate and Se were not predictive of death risk of the cohort, while vitamin B12 showed inconsistent results. Nevertheless, mortality was significantly lower at higher serum Se levels (upper quintile), but this effect was restricted to women. Higher tHcy in both sexes and lower serum Se in women were found to be independently associated with an increased risk of death in elderly subjects.
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.
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.
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.
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.
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.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
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.
Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; P
= .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; P
= .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; P
= .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; P
= .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; P
< .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 (P
= .026).
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.
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