Publications by authors named "Laureen Dartois"

30 Publications

  • Page 1 of 1

Relation between hysterectomy, oophorectomy and the risk of incident differentiated thyroid cancer: The E3N cohort.

Clin Endocrinol (Oxf) 2019 02 3;90(2):360-368. Epub 2018 Dec 3.

Service d'Endocrinologie, CHU de Rennes, Rennes, France.

Background: Thyroid cancers are threefold more frequent in women than in men. A role of reproductive or hormonal factors has been suggested but with contradictory results. We investigated potential associations between history of hysterectomy, with or without oophorectomy, and history of benign gynaecological disease (uterine fibroids, endometriosis) and the incidence of differentiated thyroid cancer, in a large French prospective cohort.

Methods: A total of 89 340 women from the E3N cohort were followed up between 1990 and 2012. Gynaecological diseases treated by surgery were self-reported. Thyroid cancers were validated by histological reports. Time-dependent covariates included smoking status, BMI and history of benign thyroid disease. Cox proportional hazard models with age as timescale were used to estimate Hazard Ratios (HR) and 95% confidence intervals (CI).

Results: A total of 412 cases of thyroid cancer were diagnosed during follow-up. A history of hysterectomy was associated with an increased risk of differentiated thyroid cancer (adjusted HR=2.05; 95%CI: 1.65-2.55). The association was not altered after further adjustment for reproductive factors. Endometriosis, uterine polyps, ovarian cysts and oophorectomy without hysterectomy were not associated with the risk of thyroid cancer. A history of fibroids was also significantly related to the risk of thyroid cancer over the follow-up period (adjusted HR=1.91; 95%CI: 1.50-2.44) and the increased risk persisted after adjustment for history of hysterectomy.

Conclusions: Women who had either a history of fibroids or hysterectomy had an increased risk of differentiated thyroid cancer. These findings suggest shared biological mechanisms between fibroids and thyroid cancer, which deserve to be further dissected.
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http://dx.doi.org/10.1111/cen.13899DOI Listing
February 2019

Population attributable fractions of the main type 2 diabetes mellitus risk factors in women: Findings from the French E3N cohort.

J Diabetes 2019 Mar 23;11(3):242-253. Epub 2018 Sep 23.

Inserm U1018, Institut Gustave Roussy, Center for Research in Epidemiology and Population Health (CESP), Villejuif, France.

Background: Although many type 2 diabetes mellitus (T2DM) risk factors have been identified, little is known regarding their contributions to the diabetes burden at the population level.

Methods: The study included 72 655 French women from the Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective cohort followed between 1993 and 2011. Cox multivariable models including the main T2DM risk factors (metabolic, dietary, clinical, socioeconomic and hormonal) and a healthy lifestyle index combining five characteristics (smoking, body mass index [BMI], alcohol consumption, fruit and vegetable consumption, and physical activity) were used to estimate hazard ratios and population attributable fractions (PAFs) for T2DM.

Results: In multivariate models, factors with the strongest effect on T2DM risk were, in decreasing order, BMI ≥ 30 kg/m (PAF = 43%; 95% confidence interval [CI] 37-47), high adherence to a Western dietary pattern (PAF = 30%; 95% CI 20-40), hypertension (PAF = 26%; 95% CI 20-32), an acidogenic diet (PAF = 24%; 95% CI 16-32), a family history of diabetes (PAF = 20%; 95% CI 17-22), and, with a negative correlation, moderate alcohol consumption (PAF-19%; 95% CI -34, -4). The PAF for an unhealthy lifestyle was 57% (95% CI 50-63).

Conclusions: We have been able to sort out and quantify the effect of various dietary and biological T2DM risk factors simultaneously in a single population, and to highlight the importance of a healthy lifestyle for primary prevention: more than half the T2DM cases could have been prevented through a healthier lifestyle.
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http://dx.doi.org/10.1111/1753-0407.12839DOI Listing
March 2019

How do self and proxy dependency evaluations agree? Results from a large cohort of older women.

Age Ageing 2018 07;47(4):619-624

MGEN Foundation for Public Health, 3 square Max-Hymans, Paris Cedex, France.

Background: epidemiological studies based on questionnaires can face difficulties when collecting data on functional ability of older people, and may thus use a proxy to obtain or confirm data. It is therefore of importance to compare data from older people and from their proxies, to establish to what extent proxies' answers can be used as a substitute or a complement in epidemiological studies on dependency.

Objective: we evaluated agreement in dependency assessment, and identified factors associated with discrepancy between older people and proxy reports, in a large postal epidemiological survey.

Methodology: autonomy of 5,164 community-dwelling women from the French E3N cohort study aged 75-83 was self- and proxy-evaluated with the instrumental activities of daily living (IADL) scales. Agreement was assessed using Cohen's Kappa coefficients, and factors associated with discrepancy were determined using logistic regression models.

Results: there was agreement between self and proxy dependency assessment in 90.8% of the women, with satisfactory Cohen's kappa. Discrepancy was associated with older age, poor self-reported health, prior low level of physical activity and the proxy being the partner.

Discussion: we found that a proxy could be a reliable source of dependency assessment in large epidemiological surveys, and that some characteristics of the older person and of the proxy could modulate the agreement between proxy- and self-dependency assessments.
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http://dx.doi.org/10.1093/ageing/afy071DOI Listing
July 2018

Micronutrient dietary patterns associated with type 2 diabetes mellitus among women of the E3N-EPIC (Etude Epidémiologique auprès de femmes de l'Education Nationale) cohort study.

J Diabetes 2018 Aug 23;10(8):665-674. Epub 2018 Mar 23.

INSERM U1018, Center for Research in Epidemiology and Population Health, Villejuif, France.

Background: Micronutrients play a key role in type 2 diabetes mellitus (T2DM), but methodological difficulties arise from their collinearity and interdependencies with foods. The aim of the present study was to identify micronutrient dietary patterns in the E3N-EPIC (Etude Epidémiologique auprès de femmes de l'Education Nationale) cohort and to investigate their association with risk of T2DM.

Methods: Principal component analysis was used to identify micronutrient patterns among 71 270 women from the E3N-EPIC cohort. Associations between micronutrient patterns and risk of T2DM were quantified by hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazards regression models, adjusted for potential confounders.

Results: Six micronutrient patterns were identified explaining 78% of the total variance in micronutrient intake. A positive association was found between T2DM and a pattern highly correlated with intake of vitamins B and B (HR 1.34; 95% CI 1.16-1.56). Similarly, a positive association was found with a pattern characterized by high intakes of vitamin B and retinol, and a low intake of vitamin C (HR 1.30; 95% CI 1.15-1.48). An inverse association was observed between T2DM and another two patterns: one correlated with magnesium and vitamin B (HR 0.75; 95% CI 0.66-0.86), and the other correlated with manganese intake (HR 0.82; 95% CI 0.72-0.94).

Conclusions: The findings of the present study identify micronutrients that have an effect on the risk of T2DM, and enable better understanding of the complexity of the diet when investigating the association between micronutrients and T2DM.
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http://dx.doi.org/10.1111/1753-0407.12654DOI Listing
August 2018

Patterns of Ultraviolet Radiation Exposure and Skin Cancer Risk: the E3N-SunExp Study.

J Epidemiol 2018 Jan 25;28(1):27-33. Epub 2017 Nov 25.

CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay.

Background: While ultraviolet (UV) radiation exposure is a recognized risk factor for skin cancer, associations are complex and few studies have allowed a direct comparison of exposure profiles associated with cutaneous melanoma, basal-cell carcinoma (BCC), and squamous-cell carcinoma (SCC) within a single population.

Methods: We examined associations between UV exposures and skin cancer risk in a nested case-control study within E3N, a prospective cohort of 98,995 French women born in 1925-1950. In 2008, a lifetime UV exposure questionnaire was sent to all reported skin cancer cases and three controls per case, which were matched on age, county of birth, and education. Analyses were performed using conditional logistic regression and included 366 melanoma cases, 1,027 BCC cases, 165 SCC cases, and 3,647 controls.

Results: A history of severe sunburns <25 years was associated with increased risks of all skin cancers (melanoma: OR 2.7; BCC: OR 1.7; SCC: OR 2.0 for ≥6 sunburns vs. none), while sunburns ≥25 years were associated with BCC and SCC only. While high-sun protection factor sunscreen use before age 25 was associated with lower BCC risk (P = 0.02), use since age 25 and reapplication of sunscreen were associated with higher risks of all three types of skin cancer. There were positive linear associations between total UV score and risks of BCC (P = 0.01) and SCC (P = 0.09), but not melanoma. While recreational UV score was strongly associated with BCC, total and residential UV scores were more strongly associated with SCC.

Conclusions: Melanoma, BCC, and SCC are associated with different sun exposure profiles in women.
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http://dx.doi.org/10.2188/jea.JE20160166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742376PMC
January 2018

Endometriosis and the risk of skin cancer: a prospective cohort study.

Cancer Causes Control 2017 Oct 10;28(10):1011-1019. Epub 2017 Aug 10.

CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, 94805, Villejuif Cedex, France.

Purpose: Endometriosis has been associated with an increased risk of skin melanoma. However, associations with other skin cancer types and how they compare with melanoma are unclear. Our objective was to prospectively investigate the relationships between endometriosis and risk of non-melanoma and melanoma skin cancers.

Methods: E3N is a prospective cohort of 98,995 French women aged 40-65 years in 1990. Data on surgically confirmed endometriosis and skin cancer diagnoses were collected every 2-3 years through self-report, with skin cancer cases confirmed through pathology reports. Hazard Ratios (HR) and 95% confidence intervals (CIs) were calculated using Cox regression models.

Results: Between 1990 and 2008, 535 melanoma, 247 squamous-cell carcinoma (SCC), and 1,712 basal-cell carcinoma (BCC) cases were ascertained. Endometriosis was associated with an increased overall risk of skin cancer (HR 1.28, 95% CI 1.05-1.55). When considering skin cancer type, endometriosis was associated with melanoma risk (HR 1.64, 95% CI 1.15-2.35), but not with SCC (HR 1.21, 95% CI 0.62-2.36) or BCC (HR 1.16, 95% CI 0.91-1.48) (non-melanoma skin cancers combined: HR 1.17, 95% CI 0.93-1.46), although no heterogeneity was detected across skin cancer types (Phomogeneity = 0.13).

Conclusion: These data support an association between a personal history of endometriosis and the risk of skin cancer and suggest that the association is strongest for melanoma.
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http://dx.doi.org/10.1007/s10552-017-0939-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693730PMC
October 2017

Tumor characteristics and family history in relation to mammographic density and breast cancer: The French E3N cohort.

Cancer Epidemiol 2017 08 8;49:156-160. Epub 2017 Jul 8.

CESP Inserm, Villejuif, France; Department of Clinical and Experimental Medicine, University of Pisa, Italy.

Background: Mammographic density is a known heritable risk factor for breast cancer, but reports how tumor characteristics and family history may modify this association are inconsistent.

Methods: Dense and total breast areas were assessed using Cumulus™ from pre-diagnostic mammograms for 820 invasive breast cancer cases and 820 matched controls nested within the French E3N cohort study. To allow comparisons across models, percent mammographic density (PMD) was standardized to the distribution of the controls. Odds ratios (OR) and 95% confidence intervals (CI) of breast cancer risk for mammographic density were estimated by conditional logistic regression while adjusting for age and body mass index. Heterogeneity according to tumor characteristic and family history was assessed using stratified analyses.

Results: Overall, the OR per 1 SD for PMD was 1.50 (95% CI, 1.33-1.69). No evidence for significant heterogeneity by tumor size, lymph node status, grade, and hormone receptor status (estrogen, progesterone, and HER2) was detected. However, the association of PMD was stronger for women reporting a family history of breast cancer (OR=2.25; 95% CI, 1.67-3.04) than in women reporting none (OR=1.41; 95% CI, 1.24-1.60; p=0.002). Similarly, effect modification by FHBC was observed using categories of PMD (p=0.02) with respective ORs of 15.16 (95% CI, 4.23-54.28) vs. 3.14 (95% CI, 1.89-5.22) for ≥50% vs. <10% PMD.

Conclusions: The stronger association between mammographic density and breast cancer risk with a family history supports the hypothesis of shared genetic factors responsible for familial aggregation of breast cancer and the heritable component of mammographic density.
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http://dx.doi.org/10.1016/j.canep.2017.07.003DOI Listing
August 2017

Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study.

Ann Intern Med 2017 Aug 11;167(4):236-247. Epub 2017 Jul 11.

From International Agency for Research on Cancer, Lyon, France; Imperial College London, London, United Kingdom; Institut Gustave Roussy, Villejuif, France; German Cancer Research Center, Heidelberg, Germany; German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; Danish Cancer Society Research Center, Copenhagen, Denmark; Aarhus University, Aarhus, Denmark; Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark; Public Health Directorate, Asturias, Spain; Catalan Institute of Oncology, Barcelona, Spain; Andalusian School of Public Health, Granada, Spain; Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastián, Spain; Murcia Regional Health Council, Murcia, Spain; Navarre Public Health Institute, Pamplona, Spain; University of Cambridge and MRC Epidemiology Unit, Cambridge, United Kingdom; University of Oxford, Oxford, United Kingdom; Hellenic Health Foundation, Athens, Greece; Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Cancer Research and Prevention Institute-ISPO, Florence, Italy; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Federico II University, Naples, Italy; "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Ragusa, Italy; National Institute for Public Health and the Environment, Bilthoven, the Netherlands; University Medical Centre, Utrecht, the Netherlands; Malmö University Hospital, Malmö, Sweden; Umeå University, Umeå, Sweden; Swedish University of Agricultural Sciences, Uppsala, Sweden; University of Tromsø, The Arctic University of Norway, Tromsø, Norway; and National Cancer Institute, Bethesda, Maryland.

Background: The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear.

Objective: To examine whether coffee consumption is associated with all-cause and cause-specific mortality.

Design: Prospective cohort study.

Setting: 10 European countries.

Participants: 521 330 persons enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition).

Measurements: Hazard ratios (HRs) and 95% CIs estimated using multivariable Cox proportional hazards models. The association of coffee consumption with serum biomarkers of liver function, inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort (n = 14 800).

Results: During a mean follow-up of 16.4 years, 41 693 deaths occurred. Compared with nonconsumers, participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality (men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend < 0.001; women: HR, 0.93 [CI, 0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend < 0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend < 0.001). Among women, there was a statistically significant inverse association of coffee drinking with circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend < 0.001) and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend = 0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI, 1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher coffee consumption was associated with lower serum alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; γ-glutamyltransferase; and, in women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels.

Limitations: Reverse causality may have biased the findings; however, results did not differ after exclusion of participants who died within 8 years of baseline. Coffee-drinking habits were assessed only once.

Conclusion: Coffee drinking was associated with reduced risk for death from various causes. This relationship did not vary by country.

Primary Funding Source: European Commission Directorate-General for Health and Consumers and International Agency for Research on Cancer.
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http://dx.doi.org/10.7326/M16-2945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788283PMC
August 2017

The association between adult attained height and sitting height with mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC).

PLoS One 2017 3;12(3):e0173117. Epub 2017 Mar 3.

Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.

Adult height and sitting height may reflect genetic and environmental factors, including early life nutrition, physical and social environments. Previous studies have reported divergent associations for height and chronic disease mortality, with positive associations observed for cancer mortality but inverse associations for circulatory disease mortality. Sitting height might be more strongly associated with insulin resistance; however, data on sitting height and mortality is sparse. Using the European Prospective Investigation into Cancer and Nutrition study, a prospective cohort of 409,748 individuals, we examined adult height and sitting height in relation to all-cause and cause-specific mortality. Height was measured in the majority of participants; sitting height was measured in ~253,000 participants. During an average of 12.5 years of follow-up, 29,810 deaths (11,931 from cancer and 7,346 from circulatory disease) were identified. Hazard ratios (HR) with 95% confidence intervals (CI) for death were calculated using multivariable Cox regression within quintiles of height. Height was positively associated with cancer mortality (men: HRQ5 vs. Q1 = 1.11, 95%CI = 1.00-1.24; women: HRQ5 vs. Q1 = 1.17, 95%CI = 1.07-1.28). In contrast, height was inversely associated with circulatory disease mortality (men: HRQ5 vs. Q1 = 0.63, 95%CI = 0.56-0.71; women: HRQ5 vs. Q1 = 0.81, 95%CI = 0.70-0.93). Although sitting height was not associated with cancer mortality, it was inversely associated with circulatory disease (men: HRQ5 vs. Q1 = 0.64, 95%CI = 0.55-0.75; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.49-0.74) and respiratory disease mortality (men: HRQ5 vs. Q1 = 0.45, 95%CI = 0.28-0.71; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.40-0.89). We observed opposing effects of height on cancer and circulatory disease mortality. Sitting height was inversely associated with circulatory disease and respiratory disease mortality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173117PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5336260PMC
August 2017

Comparison of methods for estimating the attributable risk in the context of survival analysis.

BMC Med Res Methodol 2017 01 23;17(1):10. Epub 2017 Jan 23.

Université Paris-Saclay, Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases (B2PHI), Inserm, UVSQ, Institut Pasteur, 25 rue du Dr. Roux, Paris Cedex 15, 75724, France.

Background: The attributable risk (AR) measures the proportion of disease cases that can be attributed to an exposure in the population. Several definitions and estimation methods have been proposed for survival data.

Methods: Using simulations, we compared four methods for estimating AR defined in terms of survival functions: two nonparametric methods based on Kaplan-Meier's estimator, one semiparametric based on Cox's model, and one parametric based on the piecewise constant hazards model, as well as one simpler method based on estimated exposure prevalence at baseline and Cox's model hazard ratio. We considered a fixed binary exposure with varying exposure probabilities and strengths of association, and generated event times from a proportional hazards model with constant or monotonic (decreasing or increasing) Weibull baseline hazard, as well as from a nonproportional hazards model. We simulated 1,000 independent samples of size 1,000 or 10,000. The methods were compared in terms of mean bias, mean estimated standard error, empirical standard deviation and 95% confidence interval coverage probability at four equally spaced time points.

Results: Under proportional hazards, all five methods yielded unbiased results regardless of sample size. Nonparametric methods displayed greater variability than other approaches. All methods showed satisfactory coverage except for nonparametric methods at the end of follow-up for a sample size of 1,000 especially. With nonproportional hazards, nonparametric methods yielded similar results to those under proportional hazards, whereas semiparametric and parametric approaches that both relied on the proportional hazards assumption performed poorly. These methods were applied to estimate the AR of breast cancer due to menopausal hormone therapy in 38,359 women of the E3N cohort.

Conclusion: In practice, our study suggests to use the semiparametric or parametric approaches to estimate AR as a function of time in cohort studies if the proportional hazards assumption appears appropriate.
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http://dx.doi.org/10.1186/s12874-016-0285-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259851PMC
January 2017

Associations between serum lipids and breast cancer incidence and survival in the E3N prospective cohort study.

Cancer Causes Control 2017 01 18;28(1):77-88. Epub 2016 Nov 18.

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

Purpose: Several mechanistic studies support a role of cholesterol or its metabolites in breast cancer etiology, but associations have been inconsistent in epidemiological studies. In observational studies, possible reverse causation must be accounted for using a prospective design. We investigated prospective associations between pre-diagnostic serum lipid concentrations [total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides], and both breast cancer risk and survival in the E3N cohort study.

Methods: Analyses were performed on 583 cases from the E3N prospective cohort diagnosed between 1994 and 2005, and 1,043 controls matched on date, age, recruitment center and menopausal status at blood collection. Odds ratios (OR) and 95% confidence intervals were estimated using conditional logistic regression. Risks of recurrence were estimated among cases using Cox proportional hazards model. Models were adjusted for lifestyle risk factors and mutually adjusted for lipid concentrations. Survival analyses were additionally adjusted for tumor characteristics.

Results: Overall, there was no association between any serum lipid and breast cancer risk or survival. In stratified analyses, statistically significant interaction was observed between TC and menopausal status (P  = 0.05) and between TC and waist circumference (P  = 0.03), although the ORs did not reach statistical significance in any of the strata. There was no statistically significant effect modification by BMI, time between blood donation and diagnosis or ER status.

Conclusions: Our results suggest that serum lipids are not associated with breast cancer risk overall, but that menopausal status and waist circumference should be considered in further studies.
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http://dx.doi.org/10.1007/s10552-016-0832-4DOI Listing
January 2017

Modifiable causes of premature death in middle-age in Western Europe: results from the EPIC cohort study.

BMC Med 2016 Jun 14;14:87. Epub 2016 Jun 14.

Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133, Milan, Italy.

Background: Life expectancy is increasing in Europe, yet a substantial proportion of adults still die prematurely before the age of 70 years. We sought to estimate the joint and relative contributions of tobacco smoking, hypertension, obesity, physical inactivity, alcohol and poor diet towards risk of premature death.

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

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

Conclusions: While smoking remains the predominant risk factor for premature death in Europe, poor diet, overweight and obesity, hypertension, physical inactivity, and excessive alcohol consumption also contribute substantially. Any attempt to minimise premature deaths will ultimately require all six factors to be addressed.
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http://dx.doi.org/10.1186/s12916-016-0630-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907105PMC
June 2016

Dietary antioxidant capacity and all-cause and cause-specific mortality in the E3N/EPIC cohort study.

Eur J Nutr 2017 Apr 18;56(3):1233-1243. Epub 2016 Feb 18.

CESP, Team 9, UMR-S 1018: INSERM, Gustave Roussy, Université Paris-Sud, Espace Maurice Tubiana, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France.

Purpose: The cellular oxidative stress (balance between pro-oxidant and antioxidant) may be a major risk factor for chronic diseases. Antioxidant capacity of human diet can be globally assessed through the dietary non-enzymatic antioxidant capacity (NEAC). Our aim was to investigate the relationship between the NEAC and all-cause and cause-specific mortality, and to test potential interactions with smoking status, a well-known pro-oxidant factor.

Methods: Among the French women of the E3N prospective cohort study initiated in 1990, including 4619 deaths among 1,199,011 persons-years of follow-up. A validated dietary history questionnaire assessed usual food intake; NEAC intake was estimated using a food composition table from two different methods: ferric ion reducing antioxidant power (FRAP) and total radical-trapping antioxidant parameter (TRAP). Hazard ratio (HR) estimates and 95 % confidence intervals (CI) were derived from Cox proportional hazards regression models.

Results: In multivariate analyses, FRAP dietary equivalent intake was inversely associated with mortality from all-causes (HR for the fourth vs. the first quartile: HR = 0.75, 95 % CI 0.67, 0.83, p  < 0.0001), cancer, and cardiovascular diseases. Similar results were obtained with TRAP. There was an interaction between NEAC dietary equivalent intake and smoking status for all-cause and cardiovascular disease mortality, but not cancer mortality (respectively, for FRAP, p  = 0.002; 0.013; 0.113, results were similar with TRAP), and the association was the strongest among current smokers.

Conclusion: This prospective cohort study highlights the importance of antioxidant consumption for mortality prevention, especially among current smokers.
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http://dx.doi.org/10.1007/s00394-016-1172-6DOI Listing
April 2017

Proportion of premenopausal and postmenopausal breast cancers attributable to known risk factors: Estimates from the E3N-EPIC cohort.

Int J Cancer 2016 May 4;138(10):2415-27. Epub 2016 Feb 4.

Inserm (Institut National De La Santé Et De La Recherche Médical), Centre for Research in Epidemiology and Population Health (CESP), U1018, Team 9, Villejuif, F-94805, France.

Breast cancer is the most frequently diagnosed cancer among women worldwide. Breast cancer risk factors have been widely explored individually; however, little is known about their combined impact. We included 67,634 women from the French E3N prospective cohort, aged 42-72 at baseline. During a 15-year follow-up period, 497 premenopausal and 3,138 postmenopausal invasive breast cancer cases were diagnosed. Population-attributable fractions (PAFs) were used to estimate cases proportions attributable to risk factors under hypothetical scenarios of lowest exposure. We examined overall premenopausal and postmenopausal invasive breast cancers and tumour subtypes (ER status and HER2 expression). Premenopausal breast cancer was not significantly attributable to non-behavioral (61.2%, -15.5 to 91.88%) nor to behavioral (39.9%, -71.0 to 93.9%) factors, contrary to postmenopausal breast cancer (41.9%, 4.5 to 68.7% and 53.5%, 12.8 to 78.7%, respectively). Individually, the highest statistically significant PAFs were obtained in premenopause for birth weight (33.6%, 5.7 to 56.6%) and age at menarche (19.8%, 5.2 to 33.6%) for non-behavioral factors and in postmenopause for history of benign breast diseases (14.9%, 11.6 to 18.0%) and age at menarche (9.7%, 3.9 to 15.5%) for non-behavioral factors and for body shape at menarche (17.1%, 9.7 to 24.3%), use of hormone replacement therapy (14.5%, 9.2 to 19.6%), dietary pattern (10.1%, 2.6 to 17.4%) and alcohol consumption (5.6%, 1.9 to 9.3%) for behavioral factors. These proportions were higher for ER+, HER2- and ER+/HER2- postmenopausal breast cancers. Our data support the hypothesis that in postmenopause, never starting unhealthy behaviors can reduce the number of diagnosed breast cancers.
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http://dx.doi.org/10.1002/ijc.29987DOI Listing
May 2016

Nutrient-wide association study of 57 foods/nutrients and epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study.

Am J Clin Nutr 2016 Jan 25;103(1):161-7. Epub 2015 Nov 25.

Department of Community Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Tromsø, Norway;

Background: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk.

Objective: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort.

Design: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs.

Results: None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41).

Conclusion: In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat.
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http://dx.doi.org/10.3945/ajcn.115.118588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459057PMC
January 2016

Reproductive factors and risk of mortality in the European Prospective Investigation into Cancer and Nutrition; a cohort study.

BMC Med 2015 Oct 30;13:252. Epub 2015 Oct 30.

CIBER de Epidemiología y Salud Pública (CIBERESP), Melchor Fernández Almagro, 3-5, 28029, Madrid, Spain.

Background: Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation of reproductive characteristics with all-cause and cause-specific mortality risk.

Methods: The analysis was performed within the European Investigation into Cancer and Nutrition prospective cohort study, which enrolled >500,000 women and men from 1992 to 2000, who were residing in a given town/geographic area in 10 European countries. The current analysis included 322,972 eligible women aged 25-70 years with 99 % complete follow-up for vital status. We assessed reproductive characteristics reported at the study baseline including parity, age at the first birth, breastfeeding, infertility, oral contraceptive use, age at menarche and menopause, total ovulatory years, and history of oophorectomy/hysterectomy. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality were determined using Cox proportional hazards regression models adjusted for menopausal status, body mass index, physical activity, education level, and smoking status/intensity and duration.

Results: During a mean follow-up of 12.9 years, 14,383 deaths occurred. The HR (95 % CI) for risk of all-cause mortality was lower in parous versus nulliparous women (0.80; 0.76-0.84), in women who had ever versus never breastfed (0.92; 0.87-0.97), in ever versus never users of oral contraceptives (among non-smokers; 0.90; 0.86-0.95), and in women reporting a later age at menarche (≥15 years versus <12; 0.90; 0.85-0.96; P for trend = 0.038).

Conclusions: Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes. These findings may contribute to the development of improved strategies to promote better long-term health in women.
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http://dx.doi.org/10.1186/s12916-015-0484-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627614PMC
October 2015

Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients: a cohort study.

BMC Med 2015 May 7;13:107. Epub 2015 May 7.

Department of Gastroenterology and Hepatology, University Medical Centre, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.

Background: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients.

Methods: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality.

Results: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend <0.0001), compared to participants with the lowest concordance with the recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall mortality were observed (P for trend 0.004). Meeting the recommendations on body fatness and plant food consumption were associated with improved survival among CRC cases in mutually adjusted models.

Conclusions: Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.
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http://dx.doi.org/10.1186/s12916-015-0332-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423114PMC
May 2015

A comparison between different prediction models for invasive breast cancer occurrence in the French E3N cohort.

Breast Cancer Res Treat 2015 Apr 6;150(2):415-26. Epub 2015 Mar 6.

Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health (CESP), U1018, Team 9, 114 rue Édouard Vaillant, 94805, Villejuif Cedex, France.

Breast cancer remains a global health concern with a lack of high discriminating prediction models. The k-nearest-neighbor algorithm (kNN) estimates individual risks using an intuitive tool. This study compares the performances of this approach with the Cox and the Gail models for the 5-year breast cancer risk prediction. The study included 64,995 women from the French E3N prospective cohort. The sample was divided into a learning (N = 51,821) series to learn the models using fivefold cross-validation and a validation (N = 13,174) series to evaluate them. The area under the receiver operating characteristic curve (AUC) and the expected over observed number of cases (E/O) ratio were estimated. In the two series, 393 and 78 premenopausal and 537 and 98 postmenopausal breast cancers were diagnosed. The discrimination values of the best combinations of predictors obtained from cross-validation ranged from 0.59 to 0.60. In the validation series, the AUC values in premenopausal and postmenopausal women were 0.583 [0.520; 0.646] and 0.621 [0.563; 0.679] using the kNN and 0.565 [0.500; 0.631] and 0.617 [0.561; 0.673] using the Cox model. The E/O ratios were 1.26 and 1.28 in premenopausal women and 1.44 and 1.40 in postmenopausal women. The applied Gail model provided AUC values of 0.614 [0.554; 0.675] and 0.549 [0.495; 0.604] and E/O ratios of 0.78 and 1.12. This study shows that the prediction performances differed according to menopausal status when using parametric statistical tools. The k-nearest-neighbor approach performed well, and discrimination was improved in postmenopausal women compared with the Gail model.
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http://dx.doi.org/10.1007/s10549-015-3321-7DOI Listing
April 2015

Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition cohort study.

Int J Cancer 2015 Jun 16;136(11):2640-8. Epub 2014 Nov 16.

International Agency for Research on Cancer (IARC), Lyon, France; Centre for Public Health Research, Massey University, Wellington, New Zealand.

Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed at baseline. The HLIS was constructed from five factors (diet, physical activity, smoking, alcohol consumption and anthropometry) by assigning scores of 0-4 to categories of each component, for which higher values indicate healthier behaviours. Hazard ratios (HR) were estimated by Cox proportional regression models. During 10.9 years of median follow-up, 7,756 incident breast cancer cases were identified. There was a 3% lower risk of breast cancer per point increase of the HLIS. Breast cancer risk was inversely associated with a high HLIS when fourth versus second (reference) categories were compared [adjusted HR = 0.74; 95% confidence interval (CI): 0.66-0.83]. The fourth versus the second category of the HLIS was associated with a lower risk for hormone receptor double positive (adjusted HR = 0.81, 95% CI: 0.67-0.98) and hormone receptor double negative breast cancer (adjusted HR = 0.60, 95% CI: 0.40-0.90). Findings suggest having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women. Programmes which engage women in long term health behaviours should be supported.
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http://dx.doi.org/10.1002/ijc.29315DOI Listing
June 2015

Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

Eur J Epidemiol 2015 Jan 7;30(1):57-70. Epub 2014 Nov 7.

Department of Community Medicine, UiT-The Arctic University of Norway, Tromsö, Norway,

Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992-1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99% confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p < 0.000) with fatty fish consumption and total mortality and with total fish consumption and cancer mortality (p = 0.046).
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http://dx.doi.org/10.1007/s10654-014-9966-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356893PMC
January 2015

Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study.

BMC Med 2014 Oct 10;12:168. Epub 2014 Oct 10.

Cancer Registry and Histopathology Unit, "M.P.Arezzo" Hospital, Ragusa, Italy.

Background: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors--healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated.

Results: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend<0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend<0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend<0.0001) for rectal cancer, respectively (P-difference by cancer sub-site=0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index.

Conclusions: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.
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http://dx.doi.org/10.1186/s12916-014-0168-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192278PMC
October 2014

Fruit and vegetable intake and cause-specific mortality in the EPIC study.

Eur J Epidemiol 2014 Sep 26;29(9):639-52. Epub 2014 Aug 26.

Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands,

Consumption of fruits and vegetables is associated with a lower overall mortality. The aim of this study was to identify causes of death through which this association is established. More than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition study were included, of which 25,682 were reported deceased after 13 years of follow-up. Information on lifestyle, diet and vital status was collected through questionnaires and population registries. Hazard ratios (HR) with 95% confidence intervals (95% CI) for death from specific causes were calculated from Cox regression models, adjusted for potential confounders. Participants reporting consumption of more than 569 g/day of fruits and vegetables had lower risks of death from diseases of the circulatory (HR for upper fourth 0.85, 95% CI 0.77-0.93), respiratory (HR for upper fourth 0.73, 95% CI 0.59-0.91) and digestive system (HR for upper fourth 0.60, 95% CI 0.46-0.79) when compared with participants consuming less than 249 g/day. In contrast, a positive association with death from diseases of the nervous system was observed. Inverse associations were generally observed for vegetable, but not for fruit consumption. Associations were more pronounced for raw vegetable consumption, when compared with cooked vegetable consumption. Raw vegetable consumption was additionally inversely associated with death from neoplasms and mental and behavioral disorders. The lower risk of death associated with a higher consumption of fruits and vegetables may be derived from inverse associations with diseases of the circulatory, respiratory and digestive system, and may depend on the preparation of vegetables and lifestyle factors.
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http://dx.doi.org/10.1007/s10654-014-9945-9DOI Listing
September 2014

Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study.

Lancet Diabetes Endocrinol 2014 Oct 5;2(10):810-8. Epub 2014 Aug 5.

Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark; Aalborg University Hospital, Aalborg, Denmark.

Background: Conflicting evidence exists regarding the association between saturated fatty acids (SFAs) and type 2 diabetes. In this longitudinal case-cohort study, we aimed to investigate the prospective associations between objectively measured individual plasma phospholipid SFAs and incident type 2 diabetes in EPIC-InterAct participants.

Methods: The EPIC-InterAct case-cohort study includes 12,403 people with incident type 2 diabetes and a representative subcohort of 16,154 individuals who were selected from a cohort of 340.234 European participants with 3·99 million person-years of follow-up (the EPIC study). Incident type 2 diabetes was ascertained until Dec 31, 2007, by a review of several sources of evidence. Gas chromatography was used to measure the distribution of fatty acids in plasma phospholipids (mol%); samples from people with type 2 diabetes and subcohort participants were processed in a random order by centre, and laboratory staff were masked to participant characteristics. We estimated country-specific hazard ratios (HRs) for associations per SD of each SFA with incident type 2 diabetes using Prentice-weighted Cox regression, which is weighted for case-cohort sampling, and pooled our findings using random-effects meta-analysis.

Findings: SFAs accounted for 46% of total plasma phospholipid fatty acids. In adjusted analyses, different individual SFAs were associated with incident type 2 diabetes in opposing directions. Even-chain SFAs that were measured (14:0 [myristic acid], 16:0 [palmitic acid], and 18:0 [stearic acid]) were positively associated with incident type 2 diabetes (HR [95% CI] per SD difference: myristic acid 1·15 [95% CI 1·09-1·22], palmitic acid 1·26 [1·15-1·37], and stearic acid 1·06 [1·00-1·13]). By contrast, measured odd-chain SFAs (15:0 [pentadecanoic acid] and 17:0 [heptadecanoic acid]) were inversely associated with incident type 2 diabetes (HR [95% CI] per 1 SD difference: 0·79 [0·73-0·85] for pentadecanoic acid and 0·67 [0·63-0·71] for heptadecanoic acid), as were measured longer-chain SFAs (20:0 [arachidic acid], 22:0 [behenic acid], 23:0 [tricosanoic acid], and 24:0 [lignoceric acid]), with HRs ranging from 0·72 to 0·81 (95% CIs ranging between 0·61 and 0·92). Our findings were robust to a range of sensitivity analyses.

Interpretation: Different individual plasma phospholipid SFAs were associated with incident type 2 diabetes in opposite directions, which suggests that SFAs are not homogeneous in their effects. Our findings emphasise the importance of the recognition of subtypes of these fatty acids. An improved understanding of differences in sources of individual SFAs from dietary intake versus endogenous metabolism is needed.

Funding: EU FP6 programme, Medical Research Council Epidemiology Unit, Medical Research Council Human Nutrition Research, and Cambridge Lipidomics Biomarker Research Initiative.
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http://dx.doi.org/10.1016/S2213-8587(14)70146-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196248PMC
October 2014

Lifetime alcohol use and overall and cause-specific mortality in the European Prospective Investigation into Cancer and nutrition (EPIC) study.

BMJ Open 2014 Jul 3;4(7):e005245. Epub 2014 Jul 3.

Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.

Objectives: To investigate the role of factors that modulate the association between alcohol and mortality, and to provide estimates of absolute risk of death.

Design: The European Prospective Investigation into Cancer and nutrition (EPIC).

Setting: 23 centres in 10 countries.

Participants: 380 395 men and women, free of cancer, diabetes, heart attack or stroke at enrolment, followed up for 12.6 years on average.

Main Outcome Measures: 20 453 fatal events, of which 2053 alcohol-related cancers (ARC, including cancers of upper aerodigestive tract, liver, colorectal and female breast), 4187 cardiovascular diseases/coronary heart disease (CVD/CHD), 856 violent deaths and injuries. Lifetime alcohol use was assessed at recruitment.

Results: HRs comparing extreme drinkers (≥30 g/day in women and ≥60 g/day in men) to moderate drinkers (0.1-4.9 g/day) were 1.27 (95% CI 1.13 to 1.43) in women and 1.53 (1.39 to 1.68) in men. Strong associations were observed for ARC mortality, in men particularly, and for violent deaths and injuries, in men only. No associations were observed for CVD/CHD mortality among drinkers, whereby HRs were higher in never compared to moderate drinkers. Overall mortality seemed to be more strongly related to beer than wine use, particularly in men. The 10-year risks of overall death for women aged 60 years, drinking more than 30 g/day was 5% and 7%, for never and current smokers, respectively. Corresponding figures in men consuming more than 60 g/day were 11% and 18%, in never and current smokers, respectively. In competing risks analyses, mortality due to CVD/CHD was more pronounced than ARC in men, while CVD/CHD and ARC mortality were of similar magnitude in women.

Conclusions: In this large European cohort, alcohol use was positively associated with overall mortality, ARC and violent death and injuries, but marginally to CVD/CHD. Absolute risks of death observed in EPIC suggest that alcohol is an important determinant of total mortality.
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http://dx.doi.org/10.1136/bmjopen-2014-005245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091394PMC
July 2014

Non-invasive risk scores for prediction of type 2 diabetes (EPIC-InterAct): a validation of existing models.

Lancet Diabetes Endocrinol 2014 Jan 8;2(1):19-29. Epub 2013 Oct 8.

Cancer Research and Prevention Institute, Florence, Italy.

Background: The comparative performance of existing models for prediction of type 2 diabetes across populations has not been investigated. We validated existing non-laboratory-based models and assessed variability in predictive performance in European populations.

Methods: We selected non-invasive prediction models for incident diabetes developed in populations of European ancestry and validated them using data from the EPIC-InterAct case-cohort sample (27,779 individuals from eight European countries, of whom 12,403 had incident diabetes). We assessed model discrimination and calibration for the first 10 years of follow-up. The models were first adjusted to the country-specific diabetes incidence. We did the main analyses for each country and for subgroups defined by sex, age (<60 years vs ≥60 years), BMI (<25 kg/m(2)vs ≥25 kg/m(2)), and waist circumference (men <102 cm vs ≥102 cm; women <88 cm vs ≥88 cm).

Findings: We validated 12 prediction models. Discrimination was acceptable to good: C statistics ranged from 0·76 (95% CI 0·72-0·80) to 0·81 (0·77-0·84) overall, from 0·73 (0·70-0·76) to 0·79 (0·74-0·83) in men, and from 0·78 (0·74-0·82) to 0·81 (0·80-0·82) in women. We noted significant heterogeneity in discrimination (pheterogeneity<0·0001) in all but one model. Calibration was good for most models, and consistent across countries (pheterogeneity>0·05) except for three models. However, two models overestimated risk, DPoRT by 34% (95% CI 29-39%) and Cambridge by 40% (28-52%). Discrimination was always better in individuals younger than 60 years or with a low waist circumference than in those aged at least 60 years or with a large waist circumference. Patterns were inconsistent for BMI. All models overestimated risks for individuals with a BMI of <25 kg/m(2). Calibration patterns were inconsistent for age and waist-circumference subgroups.

Interpretation: Existing diabetes prediction models can be used to identify individuals at high risk of type 2 diabetes in the general population. However, the performance of each model varies with country, age, sex, and adiposity.

Funding: The European Union.
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http://dx.doi.org/10.1016/S2213-8587(13)70103-7DOI Listing
January 2014

Association between five lifestyle habits and cancer risk: results from the E3N cohort.

Cancer Prev Res (Phila) 2014 May 26;7(5):516-25. Epub 2014 Feb 26.

Inserm, Centre for research in Epidemiology and Population Health (CESP), 114 rue Edouard Vaillant, 94805 Villejuif, France.

Although some modifiable lifestyle characteristics have been associated with decreased cancer risk, little is known about their combined effect or about the proportion of cancer cases that could be prevented by improving lifestyle behaviors. We aimed to quantify the association between lifestyle habits and all-site and site-specific cancer risk in middle-aged women. The study included 64,732 women from the French E3N prospective cohort, ages 43 to 68 years at baseline. During a 15-year follow-up period, 6,938 cases of invasive cancer were diagnosed. We defined an index that aggregated five lifestyle characteristics: smoking, body mass index, alcohol consumption, fruit and vegetable consumption, and physical activity. Proportional hazard Cox regressions were performed to evaluate the association between lifestyle and cancer risk and to estimate multivariate HRs and their 95% confidence intervals (CI). In addition, population-attributable fractions were used to estimate the proportion of cancer cases that could be prevented by healthier behaviors. A significant decrease in all-site cancer risk was observed and was associated with a healthy lifestyle (HR, 0.81; 95% CI, 0.73-0.89 when comparing the highest with the lowest health index category; Ptrend across categories < 0.01). Combining all five characteristics would have prevented 6.3% (2.2%-10.3%) of any-site, 6.3% (0.5%-12.1%) of postmenopausal breast, and 47.5% (26.8%-64.1%) of lung cancers. In conclusion, compliance with only five modifiable lifestyle behaviors could prevent a significant number of cancers, notably postmenopausal breast and lung cancers.
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http://dx.doi.org/10.1158/1940-6207.CAPR-13-0325DOI Listing
May 2014

Development and validation of a risk score predicting substantial weight gain over 5 years in middle-aged European men and women.

PLoS One 2013 16;8(7):e67429. Epub 2013 Jul 16.

Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.

Background: Identifying individuals at high risk of excess weight gain may help targeting prevention efforts at those at risk of various metabolic diseases associated with weight gain. Our aim was to develop a risk score to identify these individuals and validate it in an external population.

Methods: We used lifestyle and nutritional data from 53°758 individuals followed for a median of 5.4 years from six centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) to develop a risk score to predict substantial weight gain (SWG) for the next 5 years (derivation sample). Assuming linear weight gain, SWG was defined as gaining ≥ 10% of baseline weight during follow-up. Proportional hazards models were used to identify significant predictors of SWG separately by EPIC center. Regression coefficients of predictors were pooled using random-effects meta-analysis. Pooled coefficients were used to assign weights to each predictor. The risk score was calculated as a linear combination of the predictors. External validity of the score was evaluated in nine other centers of the EPIC study (validation sample).

Results: Our final model included age, sex, baseline weight, level of education, baseline smoking, sports activity, alcohol use, and intake of six food groups. The model's discriminatory ability measured by the area under a receiver operating characteristic curve was 0.64 (95% CI = 0.63-0.65) in the derivation sample and 0.57 (95% CI = 0.56-0.58) in the validation sample, with variation between centers. Positive and negative predictive values for the optimal cut-off value of ≥ 200 points were 9% and 96%, respectively.

Conclusion: The present risk score confidently excluded a large proportion of individuals from being at any appreciable risk to develop SWG within the next 5 years. Future studies, however, may attempt to further refine the positive prediction of the score.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0067429PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713004PMC
February 2014

Adherence to the World Cancer Research Fund/American Institute for Cancer Research guidelines and risk of death in Europe: results from the European Prospective Investigation into Nutrition and Cancer cohort study1,4.

Am J Clin Nutr 2013 May 3;97(5):1107-20. Epub 2013 Apr 3.

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.

Background: In 2007, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) issued recommendations on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence.

Objective: We investigated whether concordance with WCRF/AICR recommendations is related to risk of death.

Design: The current study included 378,864 participants from 9 European countries enrolled in the European Prospective Investigation into Cancer and Nutrition study. At recruitment (1992-1998), dietary, anthropometric, and lifestyle information was collected. A WCRF/AICR score, which incorporated 6 of the WCRF/AICR recommendations for men [regarding body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, and alcoholic drinks (score range: 0-6)] and 7 WCRF/AICR recommendations for women [plus breastfeeding (score range: 0-7)], was constructed. Higher scores indicated greater concordance with WCRF/AICR recommendations. Associations between the WCRF/AICR score and risks of total and cause-specific death were estimated by using Cox regression analysis.

Results: After a median follow-up time of 12.8 y, 23,828 deaths were identified. Participants within the highest category of the WCRF/AICR score (5-6 points in men; 6-7 points in women) had a 34% lower hazard of death (95% CI: 0.59, 0.75) compared with participants within the lowest category of the WCRF/AICR score (0-2 points in men; 0-3 points in women). Significant inverse associations were observed in all countries. The WCRF/AICR score was also significantly associated with a lower hazard of dying from cancer, circulatory disease, and respiratory disease.

Conclusion: Results of this study suggest that following WCRF/AICR recommendations could significantly increase longevity.
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http://dx.doi.org/10.3945/ajcn.112.049569DOI Listing
May 2013

Combined impact of lifestyle factors on prospective change in body weight and waist circumference in participants of the EPIC-PANACEA study.

PLoS One 2012 30;7(11):e50712. Epub 2012 Nov 30.

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

Background: The evidence that individual dietary and lifestyle factors influence a person's weight and waist circumference is well established; however their combined impact is less well documented. Therefore, we investigated the combined effect of physical activity, nutrition and smoking status on prospective gain in body weight and waist circumference.

Methods: We used data of the prospective EPIC-PANACEA study. Between 1992 and 2000, 325,537 participants (94,445 men and 231,092 women, aged between 25-70) were recruited from nine European countries. Participants were categorised into two groups (positive or negative health behaviours) for each of the following being physically active, adherent to a healthy (Mediterranean not including alcohol) diet, and never-smoking for a total score ranging from zero to three. Anthropometric measures were taken at baseline and were mainly self-reported after a medium follow-up time of 5 years.

Results: Mixed-effects linear regression models adjusted for age, educational level, alcohol consumption, baseline body mass index and follow-up time showed that men and women who reported to be physically active, never-smoking and adherent to the Mediterranean diet gained over a 5-year period 537 (95% CI -706, -368) and 200 (-478, -87) gram less weight and 0.95 (-1.27, -0.639) and 0.99 (-1.29, -0.69) cm less waist circumference, respectively, compared to participants with zero healthy behaviours.

Conclusion: The combination of positive health behaviours was associated with significantly lower weight and waist circumference gain.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0050712PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511344PMC
May 2013

Fiber intake and total and cause-specific mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

Am J Clin Nutr 2012 Jul 30;96(1):164-74. Epub 2012 May 30.

School of Public Health, Imperial College London, London, United Kingdom.

Background: Previous studies have shown that high fiber intake is associated with lower mortality. However, little is known about the association of dietary fiber with specific causes of death other than cardiovascular disease (CVD).

Objective: The aim of this study was to assess the relation between fiber intake, mortality, and cause-specific mortality in a large European prospective study of 452,717 men and women.

Design: HRs and 95% CIs were estimated by using Cox proportional hazards models, stratified by age, sex, and center and adjusted for education, smoking, alcohol consumption, BMI, physical activity, total energy intake, and, in women, ever use of menopausal hormone therapy.

Results: During a mean follow-up of 12.7 y, a total of 23,582 deaths were recorded. Fiber intake was inversely associated with total mortality (HR(per 10-g/d increase): 0.90; 95% CI: 0.88, 0.92); with mortality from circulatory (HR(per 10-g/d increase): 0.90 and 0.88 for men and women, respectively), digestive (HR: 0.61 and 0.64), respiratory (HR: 0.77 and 0.62), and non-CVD noncancer inflammatory (HR: 0.85 and 0.80) diseases; and with smoking-related cancers (HR: 0.86 and 0.89) but not with non-smoking-related cancers (HR: 1.05 and 0.97). The associations were more evident for fiber from cereals and vegetables than from fruit. The associations were similar across BMI and physical activity categories but were stronger in smokers and participants who consumed >18 g alcohol/d.

Conclusions: Higher fiber intake is associated with lower mortality, particularly from circulatory, digestive, and non-CVD noncancer inflammatory diseases. Our results support current recommendations of high dietary fiber intake for health maintenance.
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http://dx.doi.org/10.3945/ajcn.111.028415DOI Listing
July 2012