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.

The association between lifestyle and survival after colorectal cancer has received limited attention. The female sex hormone, oestrogen, has been associated with lower colorectal cancer risk and mortality after colorectal cancer. Phyto-oestrogens are plant compounds with structure similar to oestrogen, and the main sources in Western populations are plant lignans. We investigated the association between the main lignan metabolite, enterolactone and survival after colorectal cancer among participants in the Danish Diet, Cancer and Health cohort. Prediagnosis plasma samples and lifestyle data, and clinical data from time of diagnosis from 416 women and 537 men diagnosed with colorectal cancer were used. Enterolactone was measured in plasma using a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. Participants were followed from date of diagnosis until death or end of follow-up. During this time, 210 women and 325 men died (170 women and 215 men died due to colorectal cancer). The Cox proportional hazards model was used to estimate hazard ratios (HR) and 95 % CI. Enterolactone concentrations were associated with lower colorectal cancer-specific mortality among women (HRper doubling: 0·88, 95 % CI 0·80, 0·97, P=0·0123). For men, on the contrary, enterolactone concentrations were associated with higher colorectal cancer-specific mortality (HRper doubling: 1·10, 95 % CI 1·01, 1·21, P=0·0379). The use of antibiotics affects enterolactone production, and the associations between higher enterolactone and lower colorectal cancer-specific mortality were more pronounced among women who did not use antibiotics (analysis on a subset). Our results suggest that enterolactone is associated with lower risk of mortality among women, but the opposite association was found among men.

Potatoes have been a staple food in many countries throughout the years. Potatoes have a high glycaemic index (GI) score, and high GI has been associated with several chronic diseases and cancers. Still, the research on potatoes and health is scarce and contradictive, and we identified no prospective studies that had investigated the association between potatoes as a single food and the risk of pancreatic cancer. The aim of this study was to prospectively investigate the association between potato consumption and pancreatic cancer among 114 240 men and women in the prospective HELGA cohort, using Cox proportional hazard models. Information on diet (validated FFQ’s), lifestyle and health was collected by means of a questionnaire, and 221 pancreatic cancer cases were identified through cancer registries. The mean follow-up time was 11·4 (95 % CI 0·3, 16·9) years. High consumption of potatoes showed a non-significantly higher risk of pancreatic cancer in the adjusted model (hazard ratio (HR) 1·44; 95 % CI 0·93, 2·22, Pfor trend 0·030) when comparing the highest v. the lowest quartile of potato consumption. In the sex-specific analyses, significant associations were found for females (HR 2·00; 95 % CI 1·07, 3·72, Pfor trend 0·020), but not for males (HR 1·01; 95 % CI 0·56, 1·84, Pfor trend 0·34). In addition, we explored the associations by spline regression, and the absence of dose–response effects was confirmed. In this study, high potato consumption was not consistently associated with a higher risk of pancreatic cancer. Further studies with larger populations are needed to explore the possible sex difference.

According to World Cancer Research Fund International/American Institute for Cancer Research, it is ‘probable’ that dairy products decrease the risk of colorectal cancer (CRC). However, meta-analyses restricted to women have not shown associations between milk intake and risk of CRC. The aim of this study was to examine the association between milk intake and risk of CRC, colon cancer and rectal cancer among women. Data from 81 675 participants in the Norwegian Women and Cancer Cohort Study were included, and multivariable Cox proportional hazard regression models were used to investigate milk intake using two different analytical approaches: one that included repeated measurements and one that included baseline measurements only (872 and 1084 CRC cases, respectively). A weak inverse association between milk intake and risk of colon cancer may be indicated both in repeated measurements analyses and in baseline data analyses. Hazard ratios (HR) for colon cancer of 0·80 (95 % CI 0·62, 1·03, Ptrend 0·07) and 0·81 (95 % CI 0·64, 1·01, Ptrend 0·03) and HR for rectal cancer of 0·97 (95 % CI 0·67, 1·42, Ptrend 0·92) and 0·71 (95 % CI 0·50, 1·01, Ptrend 0·03) were found when comparing the high with the no/seldom milk intake group in energy-adjusted multivariable models. Our study indicates that there may be a weak inverse association between milk intake and risk of colon cancer among women. The two analytical approaches yielded different results for rectal cancer and hence CRC. Our study indicates that the use of single or repeated measurements in analyses may influence the results.

Improvements in colorectal cancer (CRC) detection and treatment have led to greater numbers of CRC survivors, for whom there is limited evidence on which to provide dietary guidelines to improve survival outcomes. Higher intake of red and processed meat and lower intake of fibre are associated with greater risk of developing CRC, but there is limited evidence regarding associations with survival after CRC diagnosis. Among 3789 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, pre-diagnostic consumption of red meat, processed meat, poultry and dietary fibre was examined in relation to CRC-specific mortality (n 1008) and all-cause mortality (n 1262) using multivariable Cox regression models, adjusted for CRC risk factors. Pre-diagnostic red meat, processed meat or fibre intakes (defined as quartiles and continuous grams per day) were not associated with CRC-specific or all-cause mortality among CRC survivors; however, a marginal trend across quartiles of processed meat in relation to CRC mortality was detected (P 0·053). Pre-diagnostic poultry intake was inversely associated with all-cause mortality among women (hazard ratio (HR)/20 g/d 0·92; 95 % CI 0·84, 1·00), but not among men (HR 1·00; 95 % CI 0·91, 1·09) (Pfor heterogeneity=0·10). Pre-diagnostic intake of red meat or fibre is not associated with CRC survival in the EPIC cohort. There is suggestive evidence of an association between poultry intake and all-cause mortality among female CRC survivors and between processed meat intake and CRC-specific mortality; however, further research using post-diagnostic dietary data is required to confirm this relationship.

Low-Se status may be associated with a higher risk of notably advanced prostate cancer. In a Danish population with a relatively low Se intake, we investigated the association between pre-diagnostic Se status and (1) the risk of total, advanced and high-grade prostate cancer and (2) all-cause and prostate cancer-specific mortality among men with prostate cancer. Within the Danish ‘Diet, Cancer and Health’ cohort, including 27 179 men, we identified 784 cases with incident prostate cancer through 2007. Each case was risk set-matched to one control. Two-thirds (n 525) of the cases had advanced disease at the time of diagnosis, and among these 170 had high-grade disease; 305 cases died (n 212 from prostate cancer) during follow-up through 2012. Plasma Se was not associated with total or advanced prostate cancer risk, but higher Se levels were associated with a lower risk of high-grade disease (HR 0·77; 95 % CI 0·64, 0·94; P=0·009). In survival analyses, a higher level of plasma Se was associated with a lower risk of all-cause (HR 0·92; 95 % CI 0·85, 1·00; P=0·04), but not prostate cancer-specific mortality. Higher levels of selenoprotein P were associated with a lower risk of high-grade disease (HR 0·85; 95 % CI 0·74, 0·97; P=0·01), but not with the risk of or mortality from advanced prostate cancer. In conclusion, levels of plasma Se and selenoprotein P were not associated with the risk of total and advanced prostate cancer, but higher levels of these two biomarkers were associated with a lower risk of high-grade disease.

No study has yet investigated the intake of different types of whole grain (WG) in relation to all-cause and cause-specific mortality in a healthy population. The aim of the present study was to investigate the intake of WG products and WG types in relation to all-cause and cause-specific mortality in a large Scandinavian HELGA cohort that, in 1992–8, included 120 010 cohort members aged 30–64 years from the Norwegian Women and Cancer Study, the Northern Sweden Health and Disease Study, and the Danish Diet Cancer and Health Study. Participants filled in a FFQ from which data on the intake of WG products were extracted. The estimation of daily intake of WG cereal types was based on country-specific products and recipes. Mortality rate ratios (MRR) and 95 % CI were estimated using the Cox proportional hazards model. A total of 3658 women and 4181 men died during the follow-up (end of follow-up was 15 April 2008 in the Danish sub-cohort, 15 December 2009 in the Norwegian sub-cohort and 15 February 2009 in the Swedish sub-cohort). In the analyses of continuous WG variables, we found lower all-cause mortality with higher intake of total WG products (women: MRR 0·89 (95 % CI 0·86, 0·91); men: MRR 0·89 (95 % CI 0·86, 0·91) for a doubling of intake). In particular, intake of breakfast cereals and non-white bread was associated with lower mortality. We also found lower all-cause mortality with total intake of different WG types (women: MRR 0·88 (95 % CI 0·86, 0·92); men: MRR 0·88 (95 % CI 0·86, 0·91) for a doubling of intake). In particular, WG oat, rye and wheat were associated with lower mortality. The associations were found in both women and men and for different causes of deaths. In the analyses of quartiles of WG intake in relation to all-cause mortality, we found lower mortality in the highest quartile compared with the lowest for breakfast cereals, non-white bread, total WG products, oat, rye (only men), wheat and total WG types. The MRR for highest v. lowest quartile of intake of total WG products was 0·68 (95 % CI 0·62, 0·75, Ptrend over quartiles< 0·0001) for women and 0·75 (95 % CI 0·68, 0·81, Ptrend over quartiles< 0·0001) for men. The MRR for highest v. lowest quartile of intake of total WG types was 0·74 (95 % CI 0·67, 0·81, Ptrend over quartiles< 0·0001) for women and 0·75 (95 % CI 0·68, 0·82, Ptrend over quartiles< 0·0001) for men. Despite lower statistical power, the analyses of cause-specific mortality according to quartiles of WG intake supported these results. In conclusion, higher intake of WG products and WG types was associated with lower mortality among participants in the HELGA cohort. The study indicates that intake of WG is an important aspect of diet in preventing early death in Scandinavia.

Individual lifestyle factors have been associated with lifestyle diseases and premature mortality by an accumulating body of evidence. The impact of a combination of lifestyle factors on mortality has been investigated in several studies, but few have applied a simple index taking national guidelines into account. The objective of the present prospective cohort study was to investigate the combined impact of adherence to five lifestyle factors (smoking, alcohol intake, physical activity, waist circumference and diet) on all-cause, cancer and cardiovascular mortality based on international and national health recommendations. A Cox proportional hazards model was used to estimate hazard ratios (HR) with 95 % CI. During a median follow-up of 14 years, 3941 men and 2827 women died. Among men, adherence to one additional health recommendation was associated with an adjusted HR of 0·73 (95 % CI 0·71, 0·75) for all-cause mortality, 0·74 (95 % CI 0·71, 0·78) for cancer mortality and 0·70 (95 % CI 0·65, 0·75) for cardiovascular mortality. Among women, the corresponding HR was 0·72 (95 % CI 0·70, 0·75) for all-cause mortality, 0·76 (95 % CI 0·73, 0·80) for cancer mortality and 0·63 (95 % CI 0·57, 0·70) for cardiovascular mortality. In the present study, adherence to merely one additional health recommendation had a protective effect on mortality risk, indicating a huge potential in enhancing healthy lifestyle behaviours of the population.

Whole-grain intake has been reported to be associated with a lower risk of several lifestyle-related diseases such as type 2 diabetes, CVD and some types of cancers. As measurement errors in self-reported whole-grain intake assessments can be substantial, dietary biomarkers are relevant to be used as complementary tools for dietary intake assessment. Alkylresorcinols (AR) are phenolic lipids found almost exclusively in whole-grain wheat and rye products among the commonly consumed foods and are considered as valid biomarkers of the intake of these products. In the present study, we analysed the plasma concentrations of five AR homologues in 2845 participants from ten European countries from a nested case–control study in the European Prospective Investigation into Cancer and Nutrition. High concentrations of plasma total AR were found in participants from Scandinavia and Central Europe and lower concentrations in those from the Mediterranean countries. The geometric mean plasma total AR concentrations were between 35 and 41 nmol/l in samples drawn from fasting participants in the Central European and Scandinavian countries and below 23 nmol/l in those of participants from the Mediterranean countries. The whole-grain source (wheat or rye) could be determined using the ratio of two of the homologues. The main source was wheat in Greece, Italy, the Netherlands and the UK, whereas rye was also consumed in considerable amounts in Germany, Denmark and Sweden. The present study demonstrates a considerable variation in the plasma concentrations of total AR and concentrations of AR homologues across ten European countries, reflecting both quantitative and qualitative differences in the intake of whole-grain wheat and rye.

The phyto-oestrogen enterolactone has been hypothesised to protect against hormone-dependent cancers, probably through its anti-oestrogenic potential. We investigated whether a higher level of plasma enterolactone was associated with a lower incidence of endometrial cancer in a case–cohort study in the ‘Diet, Cancer and Health’ cohort. The cohort study included 29 875 women aged 50–64 years enrolled between 1993 and 1997. Information on diet and lifestyle was provided by self-administrated questionnaires and blood was drawn from each participant. Time-resolved fluoroimmunoassay was used for biochemical determination of plasma enterolactone. A total of 173 cases and 149 randomly selected cohort members were included. We estimated incidence rate ratio (IRR) and 95 % CI by a Cox proportional hazards model. A 20 nmol/l higher plasma concentration of enterolactone was associated with a non-significant lower risk of endometrial cancer (IRR 0·93, 95 % CI 0·84, 1·04). When excluding women with low enterolactone concentrations (quartile 1) due to potential recent antibiotic use, the association became slightly stronger, but remained non-significant (IRR 0·90, 95 % CI 0·79, 1·02). Menopausal status, hormone replacement therapy or BMI did not modify the association. In conclusion, we found some support for a possible inverse association between plasma enterolactone concentration and endometrial cancer incidence.

Colorectal cancer (CRC) is a multi-factorial disease in which diet is believed to play a role. Little is known about the health effects of specific regional diets. The Nordic diet is high in fat and sugar but also includes a range of traditional products with anticipated health-promoting effects. The aim of this cohort study was to determine whether a healthy Nordic food index consisting of fish, cabbage, rye bread, oatmeal, apples, pears and root vegetables was related to CRC incidence. Data were obtained from a prospective cohort study of 57 053 Danish men and women aged 50–64 years, of whom 1025 developed CRC (13 years' follow-up). Incidence rate ratios (IRR) with 95 % CI were calculated from Cox proportional hazard models. Women who strongly adhered to a healthy Nordic food index had a 35 % lower incidence of CRC than women with poor adherence (adjusted IRR, 0·65; 95 % CI 0·46, 0·94); a similar tendency was found for men. Women had a 9 % lower incidence of CRC per point adherence to the healthy Nordic food index, but no significant effect was found for men. A regional diet based on healthy Nordic food items was therefore associated with a lower incidence of CRC in women. The protective effect was of the same magnitude as previously found for the Mediterranean diet, suggesting that healthy regional diets should be promoted in order to ensure health; this will also preserve cultural heredity and the environment.

Epidemiological studies suggest health-protective effects of flavan-3-ols and their derived compounds on chronic diseases. The present study aimed to estimate dietary flavan-3-ol, proanthocyanidin (PA) and theaflavin intakes, their food sources and potential determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration cohort. Dietary data were collected using a standardised 24 h dietary recall software administered to 36 037 subjects aged 35–74 years. Dietary data were linked with a flavanoid food composition database compiled from the latest US Department of Agriculture and Phenol-Explorer databases and expanded to include recipes, estimations and retention factors. Total flavan-3-ol intake was the highest in UK Health-conscious men (453·6 mg/d) and women of UK General population (377·6 mg/d), while the intake was the lowest in Greece (men: 160·5 mg/d; women: 124·8 mg/d). Monomer intake was the highest in UK General population (men: 213·5 mg/d; women: 178·6 mg/d) and the lowest in Greece (men: 26·6 mg/d in men; women: 20·7 mg/d). Theaflavin intake was the highest in UK General population (men: 29·3 mg/d; women: 25·3 mg/d) and close to zero in Greece and Spain. PA intake was the highest in Asturias (men: 455·2 mg/d) and San Sebastian (women: 253 mg/d), while being the lowest in Greece (men: 134·6 mg/d; women: 101·0 mg/d). Except for the UK, non-citrus fruits (apples/pears) were the highest contributors to the total flavan-3-ol intake. Tea was the main contributor of total flavan-3-ols in the UK. Flavan-3-ol, PA and theaflavin intakes were significantly different among all assessed groups. This study showed heterogeneity in flavan-3-ol, PA and theaflavin intake throughout the EPIC countries.