Publications by authors named "Eleni Peppa"

40 Publications

Oral factors and adherence to Mediterranean diet in an older Greek population.

Aging Clin Exp Res 2021 Apr 24. Epub 2021 Apr 24.

Department of Prosthodontics, School of Dentistry, National and Kapodistrian University of Athens, Thivon 2, 11527, Athens, Greece.

Purpose: The aim of this study was to investigate the effect of oral factors on adherence to the Mediterranean diet in an older population METHODS: 130 persons over 60 years visiting Open Care Community Centers for Older People participated in this study. Oral interviews recorded demographic and sociomedical information, subjective oral complaints, and dental habits. Adherence to Mediterranean diet was assessed using the MDI_BNC4H index (range: 0-14). An oral examination was performed, and evaluation of the masticatory performance was carried out using a two-color chewing gum that was digitally analysed.

Results: The mean age of the study participants was 73.9 ± 8.5 years. The score of adherence to the Mediterranean diet ranged from 3 to 9 (5.6 ± 1.4). 58 participants used removable prostheses, while 20 used a pair of complete dentures. Univariate analyses revealed that the parameters that negatively significantly, or marginally significantly, affected the level of adherence to the Mediterranean diet were lower masticatory performance (p = 0.050), larger number of drugs per day (p = 0.056), higher BMI (p = 0.043) and smoking (p = 0.053). The multivariable analysis revealed that lower adherence to the Mediterranean diet was significantly associated with higher BMI (p = 0.047) and lower masticatory performance (p = 0.050).

Conclusions: Increased masticatory performance was an independent predictor of better adherence to the Mediterranean diet in an older population.
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http://dx.doi.org/10.1007/s40520-021-01861-8DOI Listing
April 2021

Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer: A pooled analysis of data from two prospective cohort studies.

Int J Cancer 2021 06 22;148(11):2759-2773. Epub 2021 Feb 22.

Hellenic Health Foundation, Athens, Greece.

Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (P = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.
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http://dx.doi.org/10.1002/ijc.33504DOI Listing
June 2021

Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score.

BMC Med 2021 01 4;19(1). Epub 2021 Jan 4.

Public Health Directorate, Asturias, Spain.

Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population.

Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992-2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed.

Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell's C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264-0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084-0.575)).

Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.
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http://dx.doi.org/10.1186/s12916-020-01826-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780676PMC
January 2021

Blood polyphenol concentrations and differentiated thyroid carcinoma in women from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Am J Clin Nutr 2020 Oct 6. Epub 2020 Oct 6.

Institute of Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands.

Background: Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking.

Objectives: The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition).

Methods: A nested case-control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis.

Results: Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC.

Conclusions: Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.
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http://dx.doi.org/10.1093/ajcn/nqaa277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779226PMC
October 2020

Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality: EPIC cohort study in 10 European countries.

BMJ 2020 09 16;370:m3173. Epub 2020 Sep 16.

AOU Federico II, Naples, Italy.

Objective: To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality.

Design: Population based cohort study.

Setting: European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries.

Participants: 521 324 adults; at recruitment, country specific and validated dietary questionnaires were used to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed. The higher the score the lower the overall nutritional quality of the diet.

Main Outcome Measure: Associations between the FSAm-NPS dietary index score and mortality, assessed using multivariable adjusted Cox proportional hazards regression models.

Results: After exclusions, 501 594 adults (median follow-up 17.2 years, 8 162 730 person years) were included in the analyses. Those with a higher FSAm-NPS dietary index score (highest versus lowest fifth) showed an increased risk of all cause mortality (n=53 112 events from non-external causes; hazard ratio 1.07, 95% confidence interval 1.03 to 1.10, P<0.001 for trend) and mortality from cancer (1.08, 1.03 to 1.13, P<0.001 for trend) and diseases of the circulatory (1.04, 0.98 to 1.11, P=0.06 for trend), respiratory (1.39, 1.22 to 1.59, P<0.001), and digestive (1.22, 1.02 to 1.45, P=0.03 for trend) systems. The age standardised absolute rates for all cause mortality per 10 000 persons over 10 years were 760 (men=1237; women=563) for those in the highest fifth of the FSAm-NPS dietary index score and 661 (men=1008; women=518) for those in the lowest fifth.

Conclusions: In this large multinational European cohort, consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level.
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http://dx.doi.org/10.1136/bmj.m3173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491938PMC
September 2020

A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort.

Sci Rep 2020 09 3;10(1):14541. Epub 2020 Sep 3.

Andalusian School of Public Health (EASP), Granada, Spain.

Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI < 18.5 kg/m) or obese (BMI ≥ 30 kg/m) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
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http://dx.doi.org/10.1038/s41598-020-71302-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471961PMC
September 2020

Citrus intake and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).

Eur J Epidemiol 2020 Nov 24;35(11):1057-1067. Epub 2020 Jul 24.

CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

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 = 0.001), particularly with basal cell carcinoma (BCC) (HR = 1.11, 95% CI 1.02-1.20, P = 0.007) and squamous cell carcinoma (SCC) (HR = 1.23, 95% CI 1.04-1.47, P = 0.01). Citrus fruit intake was positively associated with skin cancer risk (HR = 1.08, 95% CI 1.01-1.16, P = 0.01), particularly with melanoma (HR = 1.23, 95% CI 1.02-1.48; P = 0.01), although with no heterogeneity across skin cancer types (P = 0.21). Citrus juice was positively associated with skin cancer risk (P = 0.004), particularly with BCC (P = 0.008) and SCC (P = 0.004), but not with melanoma (P = 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.
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http://dx.doi.org/10.1007/s10654-020-00666-9DOI Listing
November 2020

Changes in the Dietary Habits of the Greek EPIC Cohort Participants during a 14-Year Follow-Up Period (1997-2011).

Nutrients 2020 Jul 19;12(7). Epub 2020 Jul 19.

National and Kapodistrian University of Athens, 11527 Athens, Greece.

The aim of this study is to evaluate the changes in the nutritional behavior of the Greek EPIC (European Prospective Investigation into Cancer and Nutrition) cohort participants regarding the consumption of basic food groups, during a 14-year period (1997-2011). In the Greek segment of the EPIC cohort study (EPIC-Greece), the changes in dietary habits of 23,505 participants regarding several food items/groups (vegetables, legumes, fruits, nuts, dairy, cereal, meat, fish/seafood, olive oil) were recorded repeatedly over time and compared to the baseline assessment (1994-1997), using a short, qualitative, follow-up questionnaire. Descriptive statistics were used to study the trends in nutritional behavior over time and ordinal logistic regression models to study the associations between the ordered responses of the questionnaire and sociodemographic and health factors. More participants reported an increase rather than a decrease in the consumption of vegetables, fruits, fish/seafood, whilst the inverse was observed for dairy products, nuts, cereals, and meat. No prevailing trend was noted for legumes and olive oil. Factors such as being female and having high education relate to more positive (healthy) changes in nutritional behavior. There seems to be primarily a change to a more healthy nutritional behavior of the EPIC-Greece participants over the follow-up period, with different participant subgroups presenting different degrees of nutritional changes.
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http://dx.doi.org/10.3390/nu12072148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400902PMC
July 2020

A metabolomic study of red and processed meat intake and acylcarnitine concentrations in human urine and blood.

Am J Clin Nutr 2020 08;112(2):381-388

Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.

Background: Acylcarnitines (ACs) play a major role in fatty acid metabolism and are potential markers of metabolic dysfunction with higher blood concentrations reported in obese and diabetic individuals. Diet, and in particular red and processed meat intake, has been shown to influence AC concentrations but data on the effect of meat consumption on AC concentrations is limited.

Objectives: To investigate the effect of red and processed meat intake on AC concentrations in plasma and urine using a randomized controlled trial with replication in an observational cohort.

Methods: In the randomized crossover trial, 12 volunteers successively consumed 2 different diets containing either pork or tofu for 3 d each. A panel of 44 ACs including several oxidized ACs was analyzed by LC-MS in plasma and urine samples collected after the 3-d period. ACs that were associated with pork intake were then measured in urine (n = 474) and serum samples (n = 451) from the European Prospective Investigation into Cancer and nutrition (EPIC) study and tested for associations with habitual red and processed meat intake derived from dietary questionnaires.

Results: In urine samples from the intervention study, pork intake was positively associated with concentrations of 18 short- and medium-chain ACs. Eleven of these were also positively associated with habitual red and processed meat intake in the EPIC cross-sectional study. In blood, C18:0 was positively associated with red meat intake in both the intervention study (q = 0.004, Student's t-test) and the cross-sectional study (q = 0.033, linear regression).

Conclusions: AC concentrations in urine and blood were associated with red meat intake in both a highly controlled intervention study and in subjects of a cross-sectional study. Our data on the role of meat intake on this important pathway of fatty acid and energy metabolism may help understanding the role of red meat consumption in the etiology of some chronic diseases. This trial was registered at Clinicaltrials.gov as NCT03354130.
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http://dx.doi.org/10.1093/ajcn/nqaa140DOI Listing
August 2020

Menstrual Factors, Reproductive History, Hormone Use, and Urothelial Carcinoma Risk: A Prospective Study in the EPIC Cohort.

Cancer Epidemiol Biomarkers Prev 2020 08 28;29(8):1654-1664. Epub 2020 May 28.

Hellenic Health Foundation, Kaisareias 13 & Alexandroupoleos, Athens, Greece.

Background: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk.

Methods: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non-muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models.

Results: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR = 0.48; 0.25-0.90; in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03-1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non-muscle-invasive urothelial carcinoma risk was observed.

Conclusions: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk.

Impact: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0184DOI Listing
August 2020

Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk: Results from the EPIC cohort.

Int J Cancer 2020 10 24;147(8):2042-2052. Epub 2020 Apr 24.

Clinical Microbiology, Department of Translational Medicine, Lund University, Malmö, Sweden.

A substantial proportion of epithelial ovarian cancer (EOC) arises in the fallopian tube and other epithelia of the upper genital tract; these epithelia may incur damage and neoplastic transformation after sexually transmitted infections (STI) and pelvic inflammatory disease. We investigated the hypothesis that past STI infection, particularly Chlamydia trachomatis, is associated with higher EOC risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 791 cases and 1669 matched controls. Serum antibodies against C. trachomatis, Mycoplasma genitalium, herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) 16, 18 and 45 were assessed using multiplex fluorescent bead-based serology. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) comparing women with positive vs. negative serology. A total of 40% of the study population was seropositive to at least one STI. Positive serology to C. trachomatis Pgp3 antibodies was not associated with EOC risk overall, but with higher risk of the mucinous histotype (RR = 2.30 [95% CI = 1.22-4.32]). Positive serology for chlamydia heat shock protein 60 (cHSP60-1) was associated with higher risk of EOC overall (1.36 [1.13-1.64]) and with the serous subtype (1.44 [1.12-1.85]). None of the other evaluated STIs were associated with EOC risk overall; however, HSV-2 was associated with higher risk of endometrioid EOC (2.35 [1.24-4.43]). The findings of our study suggest a potential role of C. trachomatis in the carcinogenesis of serous and mucinous EOC, while HSV-2 might promote the development of endometrioid disease.
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http://dx.doi.org/10.1002/ijc.32999DOI Listing
October 2020

Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study.

Int J Cancer 2020 09 30;147(6):1649-1656. Epub 2020 Mar 30.

Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden.

Limited evidence exists on the role of modifiable lifestyle factors on the risk of lymphoma. In this work, the associations between adherence to healthy lifestyles and risks of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) were evaluated in a large-scale European prospective cohort. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 2,999 incident lymphoma cases (132 HL and 2,746 NHL) were diagnosed among 453,808 participants after 15 years (median) of follow-up. The healthy lifestyle index (HLI) score combined information on smoking, alcohol intake, diet, physical activity and BMI, with large values of HLI expressing adherence to healthy behavior. Cox proportional hazards models were used to estimate lymphoma hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses were conducted by excluding, in turn, each lifestyle factor from the HLI score. The HLI was inversely associated with HL, with HR for a 1-standard deviation (SD) increment in the score equal to 0.78 (95% CI: 0.66, 0.94). Sensitivity analyses showed that the association was mainly driven by smoking and marginally by diet. NHL risk was not associated with the HLI, with HRs for a 1-SD increment equal to 0.99 (0.95, 1.03), with no evidence for heterogeneity in the association across NHL subtypes. In the EPIC study, adherence to healthy lifestyles was not associated with overall lymphoma or NHL risk, while an inverse association was observed for HL, although this was largely attributable to smoking. These findings suggest a limited role of lifestyle factors in the etiology of lymphoma subtypes.
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http://dx.doi.org/10.1002/ijc.32977DOI Listing
September 2020

The associations of major foods and fibre with risks of ischaemic and haemorrhagic stroke: a prospective study of 418 329 participants in the EPIC cohort across nine European countries.

Eur Heart J 2020 07;41(28):2632-2640

Department of Public Health and Clinical Medicine, Umeå University, 901 87 Umeå, Sweden.

Aim: To investigate the associations between major foods and dietary fibre with subtypes of stroke in a large prospective cohort.

Methods And Results: We analysed data on 418 329 men and women from nine European countries, with an average of 12.7 years of follow-up. Diet was assessed using validated country-specific questionnaires which asked about habitual intake over the past year, calibrated using 24-h recalls. Multivariable-adjusted Cox regressions were used to estimate hazard ratios (HRs) for ischaemic and haemorrhagic stroke associated with consumption of red and processed meat, poultry, fish, dairy foods, eggs, cereals, fruit and vegetables, legumes, nuts and seeds, and dietary fibre. For ischaemic stroke (4281 cases), lower risks were observed with higher consumption of fruit and vegetables combined (HR; 95% CI per 200 g/day higher intake, 0.87; 0.82-0.93, P-trend < 0.001), dietary fibre (per 10 g/day, 0.77; 0.69-0.86, P-trend < 0.001), milk (per 200 g/day, 0.95; 0.91-0.99, P-trend = 0.02), yogurt (per 100 g/day, 0.91; 0.85-0.97, P-trend = 0.004), and cheese (per 30 g/day, 0.88; 0.81-0.97, P-trend = 0.008), while higher risk was observed with higher red meat consumption which attenuated when adjusted for the other statistically significant foods (per 50 g/day, 1.07; 0.96-1.20, P-trend = 0.20). For haemorrhagic stroke (1430 cases), higher risk was associated with higher egg consumption (per 20 g/day, 1.25; 1.09-1.43, P-trend = 0.002).

Conclusion: Risk of ischaemic stroke was inversely associated with consumption of fruit and vegetables, dietary fibre, and dairy foods, while risk of haemorrhagic stroke was positively associated with egg consumption. The apparent differences in the associations highlight the importance of examining ischaemic and haemorrhagic stroke subtypes separately.
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http://dx.doi.org/10.1093/eurheartj/ehaa007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377582PMC
July 2020

Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study.

Int J Cancer 2020 08 31;147(4):1027-1039. Epub 2020 Jan 31.

CESP, Faculté de Médecine, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.

Proinflammatory diets are associated with risk of developing colorectal cancer (CRC), however, inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute toward a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumors). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More proinflammatory diets were related to a higher CRC risk, particularly for colon cancer; hazard ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval [CI] 1.04-1.27) for CRC, 1.24 (95% CI 1.09-1.41) for colon cancer and 0.99 (95% CI 0.83-1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS was 1.62 (95% CI 1.31-2.01) for colon cancer overall and 2.11 (95% CI 1.50-2.97) for colon cancer in men. Our study shows that more proinflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men.
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http://dx.doi.org/10.1002/ijc.32870DOI Listing
August 2020

Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and risk of in situ breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BMC Med 2019 12 2;17(1):221. Epub 2019 Dec 2.

Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

Background: Even though in situ breast cancer (BCIS) accounts for a large proportion of the breast cancers diagnosed, few studies have investigated potential risk factors for BCIS. Their results suggest that some established risk factors for invasive breast cancer have a similar impact on BCIS risk, but large population-based studies on lifestyle factors and BCIS risk are lacking. Thus, we investigated the association between lifestyle and BCIS risk within the European Prospective Investigation into Cancer and Nutrition cohort.

Methods: Lifestyle was operationalized by a score reflecting the adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. The recommendations utilized in these analyses were the ones pertinent to healthy body weight, physical activity, consumption of plant-based foods, energy-dense foods, red and processed meat, and sugary drinks and alcohol, as well as the recommendation on breastfeeding. Cox proportional hazards regression was used to assess the association between lifestyle score and BCIS risk. The results were presented as hazard ratios (HR) and corresponding 95% confidence intervals (CI).

Results: After an overall median follow-up time of 14.9 years, 1277 BCIS cases were diagnosed. Greater adherence to the WCRF/AICR cancer prevention recommendations was not associated with BCIS risk (HR = 0.98, 95% CI 0.93-1.03; per one unit of increase; multivariable model). An inverse association between the lifestyle score and BCIS risk was observed in study centers, where participants were recruited mainly via mammographic screening and attended additional screening throughout follow-up (HR = 0.85, 95% CI 0.73-0.99), but not in the remaining ones (HR = 0.99, 95% CI 0.94-1.05).

Conclusions: While we did not observe an overall association between lifestyle and BCIS risk, our results indicate that lifestyle is associated with BCIS risk among women recruited via screening programs and with regular screening participation. This suggests that a true inverse association between lifestyle habits and BCIS risk in the overall cohort may have been masked by a lack of information on screening attendance. The potential inverse association between lifestyle and BCIS risk in our analyses is consistent with the inverse associations between lifestyle scores and breast cancer risk reported from previous studies.
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http://dx.doi.org/10.1186/s12916-019-1444-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886197PMC
December 2019

Development and validation of circulating CA125 prediction models in postmenopausal women.

J Ovarian Res 2019 Nov 26;12(1):116. Epub 2019 Nov 26.

CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Background: Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker.

Methods: We developed and validated linear and dichotomous (≥35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses' Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC.

Result: The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset.

Conclusions: The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.
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http://dx.doi.org/10.1186/s13048-019-0591-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878636PMC
November 2019

Healthy lifestyle and the risk of pancreatic cancer in the EPIC study.

Eur J Epidemiol 2020 Oct 28;35(10):975-986. Epub 2019 Sep 28.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLI) and waist-to-hip ratio (WHR, HLI), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants' shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLI and HLI were 0.84 (95% CI: 0.79, 0.89; p = 4.3e-09) and 0.77 (0.72, 0.82; p = 1.7e-15), respectively. Exclusions of smoking from HLI resulted in HRs of 0.88 (0.82, 0.94; p = 4.9e-04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.
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http://dx.doi.org/10.1007/s10654-019-00559-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116136PMC
October 2020

Socioeconomic Effect of Education on Pancreatic Cancer Risk in Western Europe: An Update on the EPIC Cohorts Study.

Cancer Epidemiol Biomarkers Prev 2019 06;28(6):1089-1092

Department of Public Health, Aarhus University, Aarhus, Denmark.

Background: To analyze the potential effect of social inequality on pancreatic cancer risk in Western Europe, by reassessing the association within the European Prospective Investigation into Cancer and Nutrition (EPIC) Study, including a larger number of cases and an extended follow-up.

Methods: Data on highest education attained were gathered for 459,170 participants (70% women) from 10 European countries. A relative index of inequality (RII) based on adult education was calculated for comparability across countries and generations. Cox regression models were applied to estimate relative inequality in pancreatic cancer risk, stratifying by age, gender, and center, and adjusting for known pancreatic cancer risk factors.

Results: A total of 1,223 incident pancreatic cancer cases were included after a mean follow-up of 13.9 (±4.0) years. An inverse social trend was found in models adjusted for age, sex, and center for both sexes [HR of RII, 1.27; 95% confidence interval (CI), 1.02-1.59], which was also significant among women (HR, 1.42; 95% CI, 1.05-1.92). Further adjusting by smoking intensity, alcohol consumption, body mass index, prevalent diabetes, and physical activity led to an attenuation of the RII risk and loss of statistical significance.

Conclusions: The present reanalysis does not sustain the existence of an independent social inequality influence on pancreatic cancer risk in Western European women and men, using an index based on adult education, the most relevant social indicator linked to individual lifestyles, in a context of very low pancreatic cancer survival from (quasi) universal public health systems.

Impact: The results do not support an association between education and risk of pancreatic cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-1153DOI Listing
June 2019

Consumption of nuts and seeds and pancreatic ductal adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition.

Int J Cancer 2020 01 6;146(1):76-84. Epub 2019 Jun 6.

Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

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.
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http://dx.doi.org/10.1002/ijc.32415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340534PMC
January 2020

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case-control sets from EPIC.

Int J Cancer 2020 02 29;146(3):720-730. Epub 2019 Apr 29.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR ) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR  = 0.77, 95% confidence interval 0.66-0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR  = 0.72, 0.57-0.90), or lysophosphatidylcholines (OR  = 0.81, 0.69-0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR  = 0.77, 0.61-0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.
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http://dx.doi.org/10.1002/ijc.32314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916595PMC
February 2020

Predicting Circulating CA125 Levels among Healthy Premenopausal Women.

Cancer Epidemiol Biomarkers Prev 2019 06 4;28(6):1076-1085. Epub 2019 Apr 4.

Public Health Direction and Biodonostia Research Institute and Ciberesp, Basque Regional Health Department, San Sebastian, Spain.

Background: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women.

Methods: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (≥35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC).

Results: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC ( = 0.22) and in EPIC ( = 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78).

Conclusions: We identified a combination of factors associated with CA125 levels in premenopausal women.

Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-1120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548604PMC
June 2019

Intake of individual fatty acids and risk of prostate cancer in the European prospective investigation into cancer and nutrition.

Int J Cancer 2020 01 14;146(1):44-57. Epub 2019 Mar 14.

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

The associations of individual dietary fatty acids with prostate cancer risk have not been examined comprehensively. We examined the prospective association of individual dietary fatty acids with prostate cancer risk overall, by tumor subtypes, and prostate cancer death. 142,239 men from the European Prospective Investigation into Cancer and Nutrition who were free from cancer at recruitment were included. Dietary intakes of individual fatty acids were estimated using center-specific validated dietary questionnaires at baseline and calibrated with 24-h recalls. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow-up of 13.9 years, 7,036 prostate cancer cases and 936 prostate cancer deaths were ascertained. Intakes of individual fatty acids were not related to overall prostate cancer risk. There was evidence of heterogeneity in the association of some short chain saturated fatty acids with prostate cancer risk by tumor stage (p < 0.015), with a positive association with risk of advanced stage disease for butyric acid (4:0; HR = 1.08; 95%CI = 1.01-1.15; p-trend = 0.026). There were no associations with fatal prostate cancer, with the exception of a slightly higher risk for those who consumed more eicosenoic acid (22:1n-9c; HR = 1.05; 1.00-1.11; p-trend = 0.048) and eicosapentaenoic acid (20:5n-3c; HR = 1.07; 1.00-1.14; p-trend = 0.045). There was no evidence that dietary intakes of individual fatty acids were associated with overall prostate cancer risk. However, a higher intake of butyric acid might be associated with a higher risk of advanced, whereas intakes of eicosenoic and eicosapentaenoic acids might be positively associated with fatal prostate cancer risk.
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http://dx.doi.org/10.1002/ijc.32233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899744PMC
January 2020

Adherence to the mediterranean diet and lymphoma risk in the european prospective investigation into cancer and nutrition.

Int J Cancer 2019 07 5;145(1):122-131. Epub 2019 Feb 5.

Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.

There is a growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, no prospective study has yet investigated its influence on lymphoma. We evaluated the association between adherence to the MD and risk of lymphoma and its subtypes in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The analysis included 476,160 participants, recruited from 10 European countries between 1991 and 2001. Adherence to the MD was estimated through the adapted relative MD (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for potential confounders. During an average follow-up of 13.9 years, 3,136 lymphomas (135 Hodgkin lymphoma [HL], 2,606 non-HL and 395 lymphoma not otherwise specified) were identified. Overall, a 1-unit increase in the arMED score was associated with a 2% lower risk of lymphoma (95% CI: 0.97; 1.00, p-trend = 0.03) while a statistically nonsignificant inverse association between a high versus low arMED score and risk of lymphoma was observed (hazard ratio [HR]: 0.91 [95% CI 0.80; 1.03], p-trend = 0.12). Analyses by lymphoma subtype did not reveal any statistically significant associations. Albeit with small numbers of cases (N = 135), a suggestive inverse association was found for HL (HR 1-unit increase = 0.93 [95% CI: 0.86; 1.01], p-trend = 0.07). However, the study may have lacked statistical power to detect small effect sizes for lymphoma subtype. Our findings suggest that an increasing arMED score was inversely related to the risk of overall lymphoma in EPIC but not by subtypes. Further large prospective studies are warranted to confirm these findings.
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http://dx.doi.org/10.1002/ijc.32091DOI Listing
July 2019

Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort.

Environ Res 2019 02 23;169:417-433. Epub 2018 Nov 23.

Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway.

Background: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases.

Objectives: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles.

Methods: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models.

Results: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB.

Conclusions: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.
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http://dx.doi.org/10.1016/j.envres.2018.11.027DOI Listing
February 2019

Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study.

PLoS Med 2018 09 18;15(9):e1002651. Epub 2018 Sep 18.

Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.

Background: 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.

Methods And Findings: This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus Q1 = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out.

Conclusions: In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.
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http://dx.doi.org/10.1371/journal.pmed.1002651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143197PMC
September 2018

A new food-composition database for 437 polyphenols in 19,899 raw and prepared foods used to estimate polyphenol intakes in adults from 10 European countries.

Am J Clin Nutr 2018 09;108(3):517-524

Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France.

Background: Accurate assessment of polyphenol intakes is needed in epidemiologic research in order to study their health effects, and this can be particularly challenging in international study settings.

Objective: The purpose of this work is to describe the procedures to prepare a comprehensive polyphenol food-composition database that was used to calculate standardized polyphenol intakes from 24-h diet recalls (24HDRs) and dietary questionnaires (DQs) in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Design: With the use of the comparable food classification and facet-descriptor system of the computerized 24HDR program EPIC-Soft (renamed GloboDiet), foods reported in the 24HDR (n = 74,626) were first aggregated following a stepwise process. Multi-ingredient and generic foods were broken down into ingredients or more-specific foods with consideration of regional consumption habits before matching to foods in the Phenol-Explorer database. Food-composition data were adjusted by using selected retention factors curated in Phenol-Explorer. DQ foods (n = 13,946) were matched to a generated EPIC 24HDR polyphenol-composition database before calculation of daily intakes from the 24HDR and DQ.

Results: Food matching yielded 2.0% and 2.7% of foods with missing polyphenol content in the 24HDR and DQ food data sets, respectively. Process-specific retention factors for 42 different polyphenol compounds were applied to adjust the polyphenol content in 35 prioritized Phenol-Explorer foods, thereby adjusting the polyphenol content in 70% of all of the prepared 24 food occurrences. A detailed food-composition database was finally generated for 437 polyphenols in 19,899 aggregated raw and prepared foods reported by 10 EPIC countries in the 24HDR.

Conclusions: An efficient procedure was developed to build the most-comprehensive food-composition database for polyphenols, thereby standardizing the calculations of dietary polyphenol intakes obtained from different dietary assessment methods and European populations. The whole database is accessible online. This procedure could equally be used for other food constituents and in other cohorts.
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http://dx.doi.org/10.1093/ajcn/nqy098DOI Listing
September 2018

Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke: EPIC-CVD case-cohort study.

BMJ 2018 05 29;361:k934. Epub 2018 May 29.

Public Health Directorate of Asturias, Oviedo, Spain.

Objective: To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke.

Design: Multicentre case-cohort study.

Setting: A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries.

Participants: 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison.

Main Outcome Measures: Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke).

Results: There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events.

Conclusions: Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972779PMC
http://dx.doi.org/10.1136/bmj.k934DOI Listing
May 2018

A prospective evaluation of plasma polyphenol levels and colon cancer risk.

Int J Cancer 2018 10 11;143(7):1620-1631. Epub 2018 Jun 11.

Dipartimento di Medicina Clinica e Sperimentale, Federico II University, Naples, Italy.

Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre-diagnostic plasma polyphenols and colon cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (q ) was computed to control for multiple comparisons. All statistical tests were two-sided. After false discovery rate correction and in continuous log -transformed multivariable models, equol (odds ratio [OR] per log -value, 0.86, 95% confidence interval [95% CI] = 0.79-0.93; q  = 0.01) and homovanillic acid (OR per log -value, 1.46, 95% CI = 1.16-1.84; q  = 0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR = 0.61, 95% CI = 0.41-0.91, p  = 0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR = 1.72, 95% CI = 1.17-2.53, p  < 0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis.
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http://dx.doi.org/10.1002/ijc.31563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175205PMC
October 2018

Anti-CA15.3 and Anti-CA125 Antibodies and Ovarian Cancer Risk: Results from the EPIC Cohort.

Cancer Epidemiol Biomarkers Prev 2018 07 16;27(7):790-804. Epub 2018 Apr 16.

Hellenic Health Foundation, Athens, Greece.

Neoplastic and non-neoplastic events may raise levels of mucins, CA15.3, and CA125, and generate antibodies against them, but their impact on epithelial ovarian cancer (EOC) risk has not been fully defined. CA15.3, CA125, and IgG1 antibodies against them were measured in 806 women who developed EOC and 1,927 matched controls from the European Prospective Investigation of Nutrition and Cancer. Associations between epidemiologic factors and anti-mucin antibodies were evaluated using generalized linear models; EOC risks associated with anti-mucin antibodies, by themselves or in combination with respective antigens, were evaluated using conditional logistic regression. In controls, lower antibodies against both mucins were associated with current smoking; and, in postmenopausal women, higher levels with longer oral contraceptive use and later-age-at and shorter-interval-since last birth. Lower anti-CA15.3 antibodies were associated with higher body mass and, in premenopausal women, more ovulatory cycles. Higher anti-CA15.3 and anti-CA125 antibodies were associated with higher risk for mucinous EOC occurring ≥ 3 years from enrollment. Long-term risk for serous EOC was reduced in women with low CA125 and high anti-CA125 antibodies relative to women with low concentrations of both. We found general support for the hypothesis that anti-mucin antibody levels correlate with risk factors for EOC. Antibodies alone or in combinations with their antigen may predict longer term risk of specific EOC types. Anti-CA125 and anti-CA15.3 antibodies alone or in perspective of antigens may be informative in the pathogenesis of EOC subtypes, but less useful for informing risk for all EOC. .
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http://dx.doi.org/10.1158/1055-9965.EPI-17-0744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309875PMC
July 2018

Evaluation of food photographs assessing the dietary intake of children up to 10 years old.

Public Health Nutr 2018 04 4;21(5):888-895. Epub 2017 Dec 4.

1Hellenic Health Foundation,Kaisareias 13 & Alexandroupoleos,GR-115 27 Athens,Greece.

Objective: Young children lack basic skills related to recognizing the types of foods they consume and dietary surveys often rely on parents' response. The present study aimed to evaluate how well parents of children aged from 3 months to 10 years perceive images of portions of foods commonly consumed by young children.

Design: Pre-weighed, actual food portions (n 2314) were shown to the study participants who were asked to indicate the picture that corresponded to the food in view. Mean differences between picture numbers selected and shown were estimated and compared using unpaired t tests or Tukey-Cramer pairwise comparisons.

Setting: Real-time testing of parents' perception of food images presenting portion sizes consumed by children up to 10 years old.

Subjects: A convenience sample of 138 parents/caregivers of young children (69 % females).

Results: Individuals selected the correct or adjacent image in about 97 % of the assessments. Images presenting amorphous solids (i.e. pies and pastries with a filling), liquid or semi-liquid dishes (i.e. soups, porridges, fruit and vegetable purées) were more prone to bias. There was no indication that personal characteristics (gender, age, educational background, age, number of offspring) were associated with differences in the way parents/caregivers perceived the food pictures.

Conclusions: Food pictures may not be appropriate to quantify the intake of liquid, semi-liquid or amorphous solid foods in surveys addressing young children and studies evaluating their performance as food portion anchors should ensure the inclusion of several and various amorphous foods in the assessment.
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http://dx.doi.org/10.1017/S1368980017003354DOI Listing
April 2018
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