Search

Purpose: Recent evidence suggests that plant-based diets may reduce the risk of breast cancer (BC). However, the macronutrient composition of plant-based diets and its potential impact on BC risk has not been well explored. This analysis investigated the association of macronutrient composition with BC risk across a spectrum of plant-based diet indexes using a multidimensional approach. Design: This study followed 64,655 participants from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) cohort from 1993 to 2014. Diets were evaluated using validated 208-item diet history questionnaires at baseline (1993) and follow-up (2005), to calculate adherence to the overall plant-based diet (PDI), healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI). The association of macronutrient composition with BC risk was assessed via generalized additive time-dependent Cox models across different levels of these indexes. Response surfaces were generated to visualize compositional associations at the 25th, 50th, and 75th percentile of each index (low, moderate, and high). Results: A total of 3,932 incident BC cases were identified during the 21-year follow-up. There was a significant association between macronutrient composition and BC risk for hPDI, uPDI, and PDI (all P < 0.001). Akaike information criterion favored the hPDI model for characterizing the association between macronutrients and BC. BC risk was highest for individuals with a lower hPDI score who also consumed a diet containing lower protein (10%), lower carbohydrate (35%), and higher fat (55%). The lowest risk of BC was observed in those with higher hPDI scores with the lowest intake of protein (10%). At higher PDI and uPDI, diets containing higher protein (30%) and fat (45%) had the highest BC risk. Conclusion: These results demonstrate a complex relationship between macronutrient composition, plant-based diet quality, and BC risk. Further research is needed to examine specific foods that may be driving these associations. Registry: The protocol is registered at clinicaltrials.gov as NCT03285230. [ABSTRACT FROM AUTHOR]

Many dietary guidelines recommend restricting the consumption of processed red meat (PRM) in favour of healthier foods such as fish, to reduce the risk of chronic conditions such as hypertension and diabetes. The objective of this study was to estimate the potential effect of replacing PRM for fatty fish, lean fish, red meat, eggs, pulses, or vegetables, on the risk of incident hypertension and diabetes. This was a prospective study of women in the E3N cohort study. Cases of diabetes and hypertension were based on self-report, specific questionnaires, and drug reimbursements. In the main analysis, information on regular dietary intake was assessed with a single food history questionaire, and food substitutions were modelled using cox proportional hazard models. 95 % confidence intervals were generated via bootstrapping. 71 081 women free of diabetes and 45 771 women free of hypertension were followed for an average of 18·7 and 18·3 years, respectively. 2681 incident cases of diabetes and 12 327 incident cases of hypertension were identified. Relative to PRM, fatty fish was associated with a 15 % lower risk of diabetes (HR = 0·85, 95 CI (0·73, 0·97)) and hypertension (HR = 0 85 (0·79, 0·91)). Between 3 and 10 % lower risk of hypertension or diabetes was also observed when comparing PRM with vegetables, unprocessed red meat or pulses. Relative to PRM, alternative protein sources such as fatty fish, unprocessed red meat, vegetables or pulses was associated with a lower risk of hypertension and diabetes. [ABSTRACT FROM AUTHOR]

Objectives To assess the relationship between consumption of largely consumed beverages (coffee, tea, alcohol and soft drinks) and the risk of RA. Material and methods The E3N Study (Étude Épidémiologique auprès des femmes de la Mutuelle Générale de l'Éducation Nationale) is a French prospective cohort including 98 995 women since 1990. Food and beverage consumption was assessed using a validated food-frequency questionnaire. Hazard ratios (HR) and their 95% CI for incident RA were estimated by Cox proportional hazards model. Results Among 62 631 women, 481 incident RA cases were identified. Consumptions of tea, alcohol and sugar-sweetened soft drinks were not associated with RA risk. We observed a linear association between coffee consumption and RA risk [≥4 cups/day vs ≤1cup/day, HR  =  1.24; 95% CI (0.94, 1.64), Ptrend  =  0.04], and a higher risk of RA with artificially sweetened soft drinks consumption [consumers vs not, HR  =  1.66; 95% CI (1.12, 2.45)], particularly in never-smokers. Among ever-smokers, moderate liquor intake was associated with a reduced risk of RA [1–3 glasses/week vs non-consumers, HR  =  0.63; 95% CI (0.43, 0.91)] and moderate wine consumption with a reduced risk of seropositive RA. Conclusions In a large cohort of women, tea, alcohol and sugar-sweetened soft drinks consumption was not associated with RA risk, whereas consumption of coffee (especially caffeinated coffee), and artificially sweetened soft drinks was associated with higher RA risk, particularly among never-smokers. If further confirmed, these results could lead to novel mechanistic hypotheses and to simple prevention measures. [ABSTRACT FROM AUTHOR]

Purpose: Saturated fat has long been associated with cardiovascular disease in multiple prospective studies, and randomized controlled trials. Few studies have assessed the relative associations between saturated fat and other macronutrients with hypertension, a major risk factor for cardiovascular disease. The aim of this study was to assess the relative associations between saturated fat, other macronutrients such as monounsaturated and polyunsaturated fat, proteins, and carbohydrates, and incident hypertension in a large prospective cohort of French women. Methods: This study used data from the E3N cohort study, including participants free of hypertension at baseline. A food frequency questionnaire was used to determine dietary intakes of saturated fat (SFA), monounsaturated fat (MUFA), polyunsaturated fat (PUFA), animal protein (AP), vegetable protein (VP), carbohydrates (CH) and various foods. Cases of hypertension were based on self-report, validated by drug reimbursement data. Covariates were based on self-report. Cox proportional hazard models were used to estimate the relative associations between different macronutrients and hypertension risk, using the 'substitution' framework. Bootstrapping was used to generate 95% confidence intervals. Results: This study included 45,854 women free of hypertension at baseline. During 708,887 person-years of follow-up, 12,338 incident cases of hypertension were identified. Compared to saturated fat, higher consumption of all other macronutrients was associated with a lower risk of hypertension (HRMUFA = 0.74 [0.67: 0.81], HRPUFA = 0.84 [0.77: 0.92], HRCH = 0.83 [0.77: 0.88], HRAP = 0.91 [0.85: 0.97], HRVP = 0.93 [0.83: 1.03]). Conclusion: This study finds that relative to other macronutrients such as monounsaturated or polyunsaturated fat, higher intake of saturated fat is associated with a higher risk of hypertension among women. [ABSTRACT FROM AUTHOR]

Simple Summary: (Multi-)Morbidity shares common biological mechanisms or risk factors with breast cancer. However, the risk of breast cancer among women with (multi-)morbidity remains unclear. In this study, using data of 239,436 female participants aged 40–69 of the UK Biobank cohort, we identified five chronic disease patterns: no-predominant morbidity, psychiatric morbidities, respiratory/immunological morbidities, cardiovascular/metabolic morbidities, and unspecific morbidities. After a median follow-up of 7 years, 5326 women developed breast cancer. We found no association between breast cancer risk and either the number of chronic diseases or chronic disease patterns, apart from an increased risk among women aged younger than 50 with a psychiatric pattern. Women with any multi-morbidity were more likely to die or to be diagnosed with other cancers. Our findings suggest that multi-morbidity may not be a key factor to help identify patients at an increased risk of breast cancer. (Multi-)Morbidity shares common biological mechanisms or risk factors with breast cancer. This study aimed to investigate the association between the number of morbidities and patterns of morbidity and the risk of female breast cancer. Among 239,436 women (40–69 years) enrolled in the UK Biobank cohort who had no cancer history at baseline, we identified 35 self-reported chronic diseases at baseline. We assigned individuals into morbidity patterns using agglomerative hierarchical clustering analysis. We fitted Cox models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer risk. In total, 58.4% of women had at least one morbidity, and the prevalence of multi-morbidity was 25.8%. During a median 7-year follow-up, there was no association between breast cancer risk (5326 cases) and either the number of morbidities or the identified clinically relevant morbidity patterns: no-predominant morbidity (reference), psychiatric morbidities (HR = 1.04, 95%CI 0.94–1.16), respiratory/immunological morbidities (HR = 0.98, 95%CI 0.90–1.07), cardiovascular/metabolic morbidities (HR = 0.93, 95%CI 0.81–1.06), and unspecific morbidities (HR = 0.98, 95%CI 0.89–1.07), overall. Among women younger than 50 years of age only, however, there was a significant association with psychiatric morbidity patterns compared to the no-predominant morbidity pattern (HR = 1.25, 95%CI 1.02–1.52). The other associations did not vary when stratifying by age at baseline and adherence to mammography recommendations. In conclusion, multi-morbidity was not a key factor to help identify patients at an increased risk of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Higher dietary calcium consumption is associated with lower colorectal cancer (CRC) risk. However, little data are available on the association between circulating calcium concentrations and CRC risk. Objectives: To explore the association between circulating calcium concentrations and CRC risk using data from 2 large European prospective cohort studies. Methods: Conditional logistic regression models were used to calculate multivariable-adjusted ORs and 95% CIs in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC; n-cases = 947, n-controls = 947) and the UK Biobank (UK-BB; n-cases = 2759, n-controls = 12,021) cohorts. Results: In EPIC, nonalbumin-adjusted total serum calcium (a proxy of free calcium) was not associated with CRC (OR: 0.94; 95% CI: 0.85, 1.03; modeled as continuous variable, per 1 mg/dL increase), colon cancer (OR: 0.93; 95% CI: 0.82, 1.05) or rectal cancer (OR: 1.01; 95% CI: 0.84, 1.20) risk in the multivariable adjusted model. In the UK-BB, serum ionized calcium (free calcium, most active form) was inversely associated with the risk of CRC (OR: 0.85; 95% CI: 0.76, 0.95; per 1 mg/dL) and colon cancer (OR: 0.78; 95% CI: 0.68, 0.90), but not rectal cancer (OR: 1.02; 95% CI: 0.83, 1.24) in multivariable adjusted models. Meta-analysis of EPIC and UK-BB CRC risk estimates showed an inverse risk association for CRC in the multivariable adjusted model (OR: 0.90; 95%CI: 0.84, 0.97). In analyses by quintiles, in both cohorts, higher levels of serum calcium were associated with reduced CRC risk (EPIC: ORQ5vs.Q1: 0.69; 95% CI: 0.47, 1.00; P-trend = 0.03; UK-BB: ORQ5vs.Q1: 0.82; 95% CI: 0.72, 0.94; P-trend < 0.01). Analyses by anatomical subsite showed an inverse cancer risk association in the colon (EPIC: ORQ5vs.Q1: 0.63, 95% CI: 0.39, 1.02; P-trend = 0.05; UK-BB: ORQ5vs.Q1: 0.75; 95% CI: 0.64, 0.88; P-trend < 0.01) but not the rectum. Conclusions: In UK-BB, higher serum ionized calcium levels were inversely associated with CRC, but the risk was restricted to the colon. Total serum calcium showed a null association in EPIC. Additional prospective studies in other populations are needed to better investigate these associations. [ABSTRACT FROM AUTHOR]

Purpose: Experimental studies suggested that antioxidants could protect against skin carcinomas. However, epidemiological studies on antioxidant supplement use in relation to basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) risks yielded inconsistent findings, and few prospective studies have been conducted to date. We aimed to investigate the associations between antioxidant supplement intake and keratinocyte cancer (KC) risk. Methods: E3N is an ongoing prospective cohort initiated in 1990 and involving 98,995 French women aged 40–65 years at recruitment. Intakes of dietary antioxidants were estimated via a validated dietary questionnaire in 1993 and self-reported antioxidant supplement use was collected in 1995. We used Cox models to compute hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and skin cancer risk factors. Results: Over 1995–2014, 2426 BCC and 451 SCC cases were diagnosed among 63,063 women. We found positive relationships between vitamin A supplement use and KC risk (HR = 1.37, 95% CI 1.15–1.62), particularly with BCC (HR = 1.40, 95% CI 1.17–1.69); and between vitamin E supplement use and risks of both BCC (HR = 1.21, 95% CI 1.03–1.52) and SCC (HR = 1.43, 95% CI 1.03–1.99). Intake of beta-carotene supplements was associated with an increased SCC risk (HR = 1.59, 95% CI 1.00–2.54). Vitamin C supplement use was not associated with KC risk. We found similar results when considering total antioxidant intake. Conclusions: Intakes of vitamin A or E supplements were associated with an increased KC risk in women. Further studies with information on doses and duration of supplement use and the ability to examine their underlying mechanisms are needed. [ABSTRACT FROM AUTHOR]

The article by Boonpor et al,1 recently published in I Diabetes Obesity and Metabolism i , highlights the interesting finding that, among participants enrolled in the UK Biobank, those with different diets have different total energy intake. In this work, Boonpor et al hypothesize that weight change may mediate associations between different types of diet and diabetes partly due to the differences in energy intake resulting from each diet. [Extracted from the article]

Purpose: Patterns of change from the traditional Palaeolithic lifestyle to the modern lifestyle may partly explain the epidemic proportions of non-communicable diseases (NCDs). We investigated to what extent adherence to the Palaeolithic diet (PD) and the Palaeolithic-like lifestyle was associated with type 2 diabetes (T2D) and hypertension risks. Methods: A study of 70,991 women from the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort, followed up for nearly 20 years. There were 3292 incident T2D and 12,504 incident hypertension cases that were validated. Dietary data were collected at baseline in 1993 via a food frequency questionnaire. The PD score and the Palaeolithic-like lifestyle score (PD, physical activity, smoking status, and body mass index [BMI]) were derived and considered in quintiles. Multivariable Cox regression models were employed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for incident T2D and hypertension. Results: In the fully adjusted models, a 1-SD increase of the PD score was associated with 4% and 3% lower risks of T2D and hypertension, respectively. Those in the highest versus the lowest quintile of the score had HR (95% CI) of 0.88 (0.79, 0.98) and 0.91 (0.86, 0.96) for T2D and hypertension, respectively (P-trend < 0.0001). Associations were stronger for the Palaeolithic-like lifestyle score; in the fully adjusted model, a 1-SD increase of the score was associated with 19% and 6% lower risks of T2D and hypertension, respectively. Risks lowered successively with each increase in quintile; those in the highest versus the lowest quintile had HR (95% CI) of 0.58 (0.52, 0.65) and 0.85 (0.80, 0.90) for T2D and hypertension, respectively (P-trend < 0.0001). Conclusions: Our data suggest that adhering to a PD based on fruit, vegetables, lean meats, fish, and nuts, and incorporating a Palaeolithic-like lifestyle could be promising options to prevent T2D and hypertension. [ABSTRACT FROM AUTHOR]

Objective To assess the relationships between female hormonal exposures and risk of RA in a prospective cohort of French women. Methods E3N (Etude Epidémiologique auprès des femmes de la Mutuelle générale de l'Education Nationale) is an on-going French prospective cohort that included 98 995 women aged 40–65 years in 1990. Every 2–3 years, women completed mailed questionnaires on their lifestyles, reproductive factors and health conditions. Cox proportional hazards regression models were used to determine factors associated with risk of incident RA, with age as the time scale, adjusted for known risk factors of RA, and considering endogenous and exogenous hormonal factors. Hazard ratios (HRs) and 95% CIs were estimated. Effect modification by smoking history was investigated. Results A total of 698 incident cases of RA were ascertained among 78 452 women. In multivariable-adjusted Cox regression models, risk of RA was increased with early age at first pregnancy (<22 vs ≥27 years; HR = 1.34; 95% CI 1.0, 1.7) and menopause (≤45 vs ≥53 years; HR = 1.40; 95% CI 1.0, 1.9). For early menopause, the association was of similar magnitude in ever and never smokers, although the association was statistically significant only in ever smokers (HR = 1.54; 95% CI 1.0, 2.3). We found a decreased risk in nulliparous women never exposed to smoking (HR = 0.44; 95% CI 0.2, 0.8). Risk of RA was inversely associated with exposure to progestogen only in perimenopause (>24 vs 0 months; multi-adjusted HR = 0.77; 95% CI 0.6, 0.9). Conclusions These results suggest an effect of both endogenous and exogenous hormonal exposures on RA risk and phenotype that deserves further investigation. [ABSTRACT FROM AUTHOR]

Background: Few studies have evaluated the quality of plant-based diets in relation to chronic diseases, and the potential role of BMI is not clearly explored.Objectives: To study the associations between plant-based diet indices and type 2 diabetes (T2D) and hypertension risks, as well as the extent to which the associations were modified and/or mediated by BMI.Methods: The study included 74,522 women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale prospective cohort [mean (SD): age, 52.94 (6.7) years; BMI, 22.970 (3.328) kg/m2]. Dietary data were collected at baseline (1993) via an FFQ. Overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) were developed. Multivariable Cox regression models were used to derive HRs and 95% CIs. Effect modification and mediation by BMI were explored.Results: There were 3292 (4.64%) incident cases of T2D and 12,504 (27.14%) incident cases of hypertension over ∼20 years of follow-up. In the multivariable model further adjusted for BMI, higher adherence to PDI and hPDI was associated with lower T2D and hypertension risks, with an HR per 1-SD increase (95% CI) of 0.88 (0.85, 0.91) and 0.96 (0.94, 0.98) for PDI and 0.88 (0.85, 0.92) and 0.94 (0.92, 0.95) for hPDI, respectively. uPDI was not associated with T2D [0.98 (0.94, 1.01)], whereas a positive association was observed with hypertension: 1.04 (1.02, 1.06). There was interaction between PDI and uPDI, as well as BMI, on T2D (P-interaction < 0.001) but not on hypertension (P-interaction > 0.05). In addition, BMI mediated 26-59% and 0.2-59% of diet-T2D and diet-hypertension associations, respectively.Conclusions: Differential associations between plant-based diets and T2D and hypertension risks were observed among women in this large prospective study. Only healthier plant foods were associated with lower risks, partly through decreasing BMI. The protocol was registered at clinicaltrials.gov as NCT03285230. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The Mediterranean diet has been reported to be associated with a significant reduction in risk of noncommunicable diseases. We undertook this study to assess the relationship between adherence to the Mediterranean diet and the risk of rheumatoid arthritis (RA), especially in high‐risk individuals. Methods: The E3N study (Etude Epidémiologique Auprès des Femmes de la Mutuelle Générale de l'Education Nationale) is a French prospective cohort study that has included 98,995 women since 1990. Dietary data were collected via a validated food frequency questionnaire in 1993. Adherence to the Mediterranean diet was assessed using a 9‐unit dietary score evaluating consumption of vegetables, legumes, cereal products, fish, meat, dairy products, olive oil, and alcohol. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident RA were estimated using Cox proportional hazards regression models adjusted for age and the main potential confounders, including smoking. Results: Among 62,629 women, we identified 480 incident cases of RA. In the entire study population, the Mediterranean diet adherence score was not associated with RA risk (HR 0.86 [95% CI 0.67–1.09] for high score versus low score; P for trend = 0.09); however, among ever‐smokers, a higher score was associated with a decreased risk of RA (HR 0.91 [95% CI 0.84–0.99] for 1‐point increase in score; P = 0.03). In ever‐smokers, the absolute risks of RA in those with high scores and those with low scores were 38.3 and 51.5 per 100,000 person‐years, respectively, compared to 35.8 per 100,000 person‐years in never‐smokers with high Mediterranean diet scores. Conclusion: Our results suggest that adherence to the Mediterranean diet could reduce the high risk of RA among ever‐smoking women. Our results must be confirmed in future research. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have identified a positive association between the inflammatory potential of the diet and hypertension. It is not known if BMI is an effect modifier for this association, nor if the association is dose-respondent. This study aimed to assess the association between the dietary inflammatory index (DII) and the risk of hypertension, and assess any effect modification from BMI.Methods: Data from the E3N cohort study, a French prospective population-based study initiated in 1990 was used. From the women in the study, we included those who completed a detailed diet history questionnaire, and who did not have prevalent hypertension or cardiovascular disease at baseline, resulting in 46,652 women. The adapted DII was assessed with data from the dietary questionnaire. Hypertension cases were self-reported and verified through a drug-reimbursement database. Cox proportional hazard models were used to calculate hazard ratios. Spline regression was used to determine any dose-respondent relationship.Results: During 884,267 person-years, 13,183 cases of incident hypertension were identified. The median DII in the population was slightly pro-inflammatory (DII = + 0.44). A highly pro-inflammatory diet (DII >  3.0) was associated with a slight increase in hypertension risk (HRQ1-Q5 = 1.07 [1.02, 1.13]). Evidence was observed for effect modification from BMI, with associations strongest amongst women in the 18.5-21.0 BMI range (HRQ1-Q5 = 1.17 [1.06, 1.29]). A weak dose-respondent relationship was observed.Conclusion: Evidence for a weak association between DII and hypertension was observed. Associations were stronger amongst healthy-lean women. [ABSTRACT FROM AUTHOR]

Background: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans.Methods: Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations.Results: Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (ORquartile 4 vs quartile 1= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95% CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk.Conclusions: This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive. [ABSTRACT FROM AUTHOR]

We investigated the influence of premenopausal use of progestogens on melanoma using data from E3N (Etude Epidémiologique Auprès de Femmes de l'Education Nationale), a prospective cohort of 98,995 French women, aged 40–65 years at inclusion. We used Cox models to adjust for age and melanoma risk factors. Over 1992–2008, 540 melanoma cases were ascertained among 79,558 women. We found a modest association between self-reported progestogen use and melanoma risk (hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 1.02, 1.47), which was reduced after adjustment for melanoma risk factors (HR = 1.15, 95% CI: 0.95, 1.39). There was no heterogeneity across types of progestogens (P  = 0.22), and use of multiple progestogens was positively associated with melanoma risk (HR = 1.33, 95% CI: 1.04, 1.70). Among users, we found no relationship with duration of progestogen use, age at start and last use, and time since first and last use. Although our results did not show evidence of a confounding effect of sun exposure, progestogen users had lower levels of residential sun exposure and were more likely to report sunscreen use, suggesting specific sun exposure profiles in users. Our findings do not support a strong influence of progestogens on melanoma risk. Further research is needed to confirm these results. [ABSTRACT FROM AUTHOR]

Introduction: Chronic inflammation plays a critical role in lymphomagenesis and several dietary factors seem to be involved its regulation. The aim of the current study was to assess the association between the inflammatory potential of the diet and the risk of lymphoma and its subtypes in the European Investigation into Cancer and Nutrition (EPIC) study. Methods: The analysis included 476,160 subjects with an average follow-up of 13.9 years, during which 3,136 lymphomas (135 Hodgkin lymphoma (HL), 2606 non-Hodgkin lymphoma (NHL) and 395 NOS) were identified. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated using 28 dietary components and their corresponding inflammatory weights. The association between the ISD and lymphoma risk was estimated by hazard ratios (HR) and 95% confidence intervals (CI) calculated by multivariable Cox regression models adjusted for potential confounders. Results: The ISD was not associated with overall lymphoma risk. Among lymphoma subtypes, a positive association between the ISD and mature B-cell NHL (HR for a 1-SD increase: 1.07 (95% CI 1.01; 1.14), p trend = 0.03) was observed. No statistically significant association was found among other subtypes. However, albeit with smaller number of cases, a suggestive association was observed for HL (HR for a 1-SD increase = 1.22 (95% CI 0.94; 1.57), p trend 0.13). Conclusions: Our findings suggested that a high ISD score, reflecting a pro-inflammatory diet, was modestly positively associated with the risk of B-cell lymphoma subtypes. Further large prospective studies on low-grade inflammation induced by diet are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Despite research efforts, current knowledge of the etiology of thyroid carcinoma remains limited. To explore the potential role of diet-induced inflammation, we examined the association between differentiated thyroid cancer risk and the energy-adjusted Dietary Inflammatory Index (E-DII) in a population-based case-control study conducted in New Caledonia, a Pacific archipelago with one of the highest recorded thyroid cancer incidence rates in the world. The E-DII was computed from food frequency questionnaire information on usual dietary intake. Logistic regression analyses were performed on data from 324 histologically confirmed cases of papillary or follicular carcinoma, diagnosed from 1993 to 1999, and 402 controls. Positive associations between E-DII and thyroid cancer risk were observed (comparing extreme tertiles, odds ratio = 1.67, 95% confidence interval: 1.08, 2.58; P for trend = 0.002), with stronger associations found for larger carcinomas (P for trend = 0.0005). Stratified analyses showed an increased risk of thyroid cancer associated with the E-DII among Southern province residents (P for trend = 0.003), Melanesian women (P for trend = 0.02), obese participants (P for trend = 0.006), and ever-smokers (P for trend = 0.0005). Our results suggest that a proinflammatory diet—especially when concomitant with other inflammation-inducing conditions or habits (e.g., obesity, smoking)—is associated with increased risk of thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Advanced breast cancer (BC) is associated with heavier treatments and poorer prognosis than early BC. Despite mammographic screening, advanced BC incidence remains stable. Little is known about risk factors differentially associated with advanced BC. We analyzed factors predicting for postmenopausal advanced vs. early BC in the E3N cohort. E3N has been prospectively following 98,995 French women aged 50–65 years at baseline since 1990. Hazard ratios (HRs) and 95% confidence intervals (CIs) for advanced and early invasive BC were estimated with multivariate Cox competing risk hazard models. With a median follow‐up of 15.7 years, 4,941 postmenopausal BC were diagnosed, including 1,878 (38%) advanced BC. Compared to early BC, advanced BC was differentially associated with excess weight (HR 1.39 [95% CI = 1.26–1.53] vs. 1.08 [95% CI = 1.00–1.17], phomogeneity < 0.0001) and living in a rural area (HR 1.14 [95% CI = 1.00–1.31] vs. 0.93 [95% CI = 0.82–1.04], phomogeneity 0.02). Excess weight was the only differential risk factor for advanced BC for hormone‐dependent BC and for women compliant with screening recommendations. Previous mammography was associated with reduced advanced BC risk (HR 0.86 [95% CI = 0.73–1.00]) and increased early BC risk (HR 1.36 [95% CI = 1.18–1.56], phomogeneity < 0.0001), but only for hormone‐dependent BC. Excess weight appears to be mostly associated with advanced BC, especially hormone‐dependent BC. These results add to the evidence for maintaining weight within the recommended limits. What's new? Targeting women at high risk of advanced‐stage diagnosis for personalized screening and prevention could help decrease the incidence of advanced breast cancers (BC). However, little is known about risk factors differentially associated with advanced BC. In this large prospective study, postmenopausal advanced BC is differentially associated with excess weight and living in a rural area, compared to early BC. Excess weight is the only differential risk factor for advanced hormone‐dependent BC, and for women compliant with screening recommendations. These results further support maintaining weight within the WHO recommended limits and enforcing mammographic screening as well as personalized prevention. [ABSTRACT FROM AUTHOR]

Diet is an important source of exposure to chemical compounds and estimating individual exposure is challenging and essential to study the association with long term health effects. This project aims to estimate the dietary exposure to more than 400 chemical compounds in the E3N cohort (Etude Epidémiologique après de femmes de la Mutuelle Générale de l'Education Nationale). In order to do so we developed a new database obtained by merging measures of chemical levels in commonly consumed food, from the second French Total Diet Study (TDS2), with the consumption data for food items of the E3N participants. E3N is a prospective cohort enrolled from 1990 with nearly 100,000 women aged between 40 to 65 years at inclusion. Participants complete a follow-up questionnaire every 2–3 years and dietary data were collected in 1993 and in 2005 using validated semi-quantitative food questionnaires developed according to the French meal pattern, collecting consumption information for 238 food items. The TDS2 analysed 445 different chemical substances in 186 core foods prepared as consumed. We attributed an occurrence value for each substance measured in the TDS2 study to all foods items included in the E3N food questionnaires. We identified 146 food items with a direct correspondence between the two databases. Alternatively, we attributed the weighted average of single foods using an a posteriori partition for 19 E3N food items. For 37 E3N food items not considered in the TDS2 we attributed the value of the most similar food measured in the TDS2. Overall 36 food items were excluded from the E3N-TDS2 database because no similar food was available. This study will allow estimating the dietary exposures to more than 400 chemical substances, either individually or as mixtures, in the E3N cohort, and therefore investigating their effect on the risk of chronic diseases, including cancers, diabetes, thyroid abnormalities, or ageing. [ABSTRACT FROM AUTHOR]

Purpose: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study. Methods: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires. Results: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97–1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95–1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95–1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81–0.99), but this association was based on a sub-analysis with a small number of cancer cases. Conclusions: In this large prospective study, coffee and tea consumptions were not associated with TC risk. [ABSTRACT FROM AUTHOR]

Objective: Most older adults express the wish to live at home as long as possible, thus autonomy promoting measures are essential. Hearing and visual impairments are common among older people, and they have been consistently associated with functional disability. However, longitudinal data are scarce, notably regarding dual sensory impairments (both in hearing and vision). We aimed at assessing the relationship between hearing, visual, and dual sensory impairments, and subsequent decline in instrumental activities of daily living (IADL). Design: Longitudinal. Setting: The French E3N-elderly sub-cohort. Participants: 4,010 community-dwelling older women born between 1925 and 1930, and free of IADL limitations in 2006. Measurements: Hearing and visual impairments were self-reported in 2006. IADLs were evaluated in 2006 and 2010. Results: After 4 years of follow-up, 588 women became limited in their IADLs. In logistic regression models adjusted for potential confounders, odds ratios [95% confidence interval] for developing IADL limitations were 1.18 [0.98; 1.41], 1.98 [1.26; 3.11], and 2.61 [1.50; 4.54] for hearing, visual, or both sensory impairments respectively, compared with no sensory impairment at baseline. Conclusion: Results suggest that among autonomous older women, visual, and to a lesser extent, hearing impairment, have a short-term negative impact on their ability to perform daily activities, with some evidence of a multiplicative effect between sensory impairments. Appropriate evaluation and management of sensory impaired elderly, and more particularly those with dual impairments, may contribute to prevent disability in aging. [ABSTRACT FROM AUTHOR]

The article discusses research which examined link between smoking status, passive smoking exposure in adulthood and childhood, and risk for rheumatoid arthritis (RA). Topics explored include the clinical characteristics and genetic factors which contribute to RA development, the analysis of risk associated with both active and passive smoking exposure, and the incident RA risk based on smoking status.

Objective: To examine timing of eating across ten European countries.Design: Cross-sectional analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study using standardized 24 h diet recalls collected during 1995-2000. Eleven predefined food consumption occasions were assessed during the recall interview. We present time of consumption of meals and snacks as well as the later:earlier energy intake ratio, with earlier and later intakes defined as 06.00-14.00 and 15.00-24.00 hours, respectively. Type III tests were used to examine associations of sociodemographic, lifestyle and health variables with timing of energy intake.Setting: Ten Western European countries.Subjects: In total, 22 985 women and 13 035 men aged 35-74 years (n 36 020).Results: A south-north gradient was observed for timing of eating, with later consumption of meals and snacks in Mediterranean countries compared with Central and Northern European countries. However, the energy load was reversed, with the later:earlier energy intake ratio ranging from 0·68 (France) to 1·39 (Norway) among women, and from 0·71 (Greece) to 1·35 (the Netherlands) among men. Among women, country, age, education, marital status, smoking, day of recall and season were all independently associated with timing of energy intake (all P<0·05). Among men, the corresponding variables were country, age, education, smoking, physical activity, BMI and day of recall (all P<0·05).Conclusions: We found pronounced differences in timing of eating across Europe, with later meal timetables but greater energy load earlier during the day in Mediterranean countries compared with Central and Northern European countries. [ABSTRACT FROM AUTHOR]

Background: Parity is widely recognized as protective for breast cancer, but breast cancer risk may be increased shortly after childbirth. Whether this risk varies with breastfeeding, family history of breast cancer, or specific tumor subtype has rarely been evaluated.Objective: To characterize breast cancer risk in relation to recent childbirth.Design: Pooled analysis of individual-level data from 15 prospective cohort studies.Setting: The international Premenopausal Breast Cancer Collaborative Group.Participants: Women younger than 55 years.Measurements: During 9.6 million person-years of follow-up, 18 826 incident cases of breast cancer were diagnosed. Hazard ratios (HRs) and 95% CIs for breast cancer were calculated using Cox proportional hazards regression.Results: Compared with nulliparous women, parous women had an HR for breast cancer that peaked about 5 years after birth (HR, 1.80 [95% CI, 1.63 to 1.99]) before decreasing to 0.77 (CI, 0.67 to 0.88) after 34 years. The association crossed over from positive to negative about 24 years after birth. The overall pattern was driven by estrogen receptor (ER)-positive breast cancer; no crossover was seen for ER-negative cancer. Increases in breast cancer risk after childbirth were pronounced when combined with a family history of breast cancer and were greater for women who were older at first birth or who had more births. Breastfeeding did not modify overall risk patterns.Limitations: Breast cancer diagnoses during pregnancy were not uniformly distinguishable from early postpartum diagnoses. Data on human epidermal growth factor receptor 2 (HER2) oncogene overexpression were limited.Conclusion: Compared with nulliparous women, parous women have an increased risk for breast cancer for more than 20 years after childbirth. Health care providers should consider recent childbirth a risk factor for breast cancer in young women.Primary Funding Source: The Avon Foundation, the National Institute of Environmental Health Sciences, Breast Cancer Now and the UK National Health Service, and the Institute of Cancer Research. [ABSTRACT FROM AUTHOR]

This study aimed to estimate the number of new cancer cases attributable to diet among adults aged 30–84 years in France in 2015, where convincing or probable evidence of a causal association exists, and, in a secondary analysis, where at least limited but suggestive evidence of a causal association exists. Cancer cases attributable to diet were estimated assuming a 10-year latency period. Dietary intake data were obtained from the 2006 French National Nutrition and Health Survey. Counterfactual scenarios of dietary intake were based on dietary guidelines. Corresponding risk relation estimates were obtained from meta-analyses, cohort studies and one case–control study. Cancer incidence data were obtained from the French Network of Cancer Registries. Nationally, unfavourable dietary habits led to 16 930 new cancer cases, representing 5·4 % of all new cancer cases. Low intake of fruit and dietary fibre was the largest contributor to this burden, being responsible for 4787 and 4389 new cancer cases, respectively. If this is expanded to dietary component and cancer pairs with at least limited but suggestive evidence of a causal association, 36 049 new cancer cases, representing 11·6 % of all new cancer cases, were estimated to be attributable to diet. These findings suggest that unfavourable dietary habits lead to a substantial number of new cancer cases in France; however, there is a large degree of uncertainty as to the number of cancers attributable to diet, including through indirect mechanisms such as obesity, and therefore additional research is needed to determine how diet affects cancer risk. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Studies using metabolomic data have identified metabolites from several compound classes that are associated with disease-related lifestyle factors. Objective: In this study,we identified metabolic signatures reflecting lifestyle patterns and related them to the risk of hepatocellular carcinoma (HCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Design: Within a nested case-control study of 147 incident HCC cases and 147 matched controls, partial least squares (PLS) analysis related 7 modified healthy lifestyle index (HLI) variables (diet, BMI, physical activity, lifetime alcohol, smoking, diabetes, and hepatitis) to 132 targeted serum-measured metabolites and a liver function score. The association between the resulting PLS scores and HCC risk was examined in multivariable conditional logistic regression models, where ORs and 95% CIs were computed. Results: The lifestyle component's PLS score was negatively associated with lifetime alcohol, BMI, smoking, and diabetes, and positively associated with physical activity. Its metabolic counterpart was positively related to the metabolites sphingomyelin (SM)(OH) C14:1, C16:1, and C22:2 and negatively related to glutamate, hexoses, and the diacyl-phosphatidylcholine PC aaC32:1. The lifestyle and metabolomics components were inversely associated with HCC risk, with the ORs for a 1-SD increase in scores equal to 0.53 (95% CI: 0.38, 0.74) and 0.28 (0.18, 0.43), and the associated AUCs equal to 0.64 (0.57, 0.70) and 0.74 (0.69, 0.80), respectively. Conclusions: This study identified a metabolic signature reflecting a healthy lifestyle pattern which was inversely associated with HCC risk. The metabolic profile displayed a stronger association with HCC than did the modified HLI derived from questionnaire data. Measuring a specific panel of metabolites may identify strata of the population at higher risk for HCC and can add substantial discrimination compared with questionnaire data. This trial was registered at clinicaltrials.gov as NCT03356535. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation plays a critical role in the pathogenesis of the 2 major types of gastric cancer. Several foods, nutrients, and nonnutrient food components seem to be involved in the regulation of chronic inflammation. Objective: We assessed the association between the inflammatory potential of the diet and the risk of gastric carcinoma, overall and for the 2 major subsites: cardia cancers and noncardia cancers. Design: A total of 476,160 subjects (30% men, 70% women) from the European Investigation into Cancer and Nutrition (EPIC) study were followed for 14 y, during which 913 incident cases of gastric carcinoma were identified, including 236 located in the cardia, 341 in the distal part of the stomach (noncardia), and 336 with overlapping or unknown tumor site. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated with the use of 28 dietary components and their corresponding inflammatory scores. The association between the ISD and gastric cancer risk was estimated by HRs and 95% CIs calculated by multivariate Cox regression models adjusted for confounders. Results: The inflammatory potential of the diet was associated with an increased risk of gastric cancer. The HR (95% CI) for each increase in 1 SD of the ISD were 1.25 (1.12, 1.39) for all gastric cancers, 1.30 (1.06, 1.59) for cardia cancers, and 1.07 (0.89, 1.28) for noncardia cancers. The corresponding values for the highest compared with the lowest quartiles of the ISD were 1.66 (1.26, 2.20), 1.94 (1.14, 3.30), and 1.07 (0.70, 1.70), respectively. Conclusions: Our results suggest that low-grade chronic inflammation induced by the diet may be associated with gastric cancer risk. This pattern seems to be more consistent for gastric carcinomas located in the cardia than for those located in the distal stomach. [ABSTRACT FROM AUTHOR]

Objective: To identify individual and contextual socio-economic factors associated with an increase in fruit and vegetable (F&V) consumption over a 12-year period and evaluate if some socio-economic factors were differentially associated with the change in consumption of some types of F&V.Design: Associations between increased F&V consumption and socio-economic factors were studied with multivariate logistic regression.Setting: E3N, a French prospective cohort study of 98 995 women.Subjects: E3N participants (n 58 193) with information on diet in 1993 and 2005, and numerous individual and contextual socio-economic factors available.Results: Associations between some individual socio-economic factors and changes in F&V consumption were observed. For instance, women who lived in a large household (>3 children v. no child) had higher probability of increasing their vegetable consumption (OR=1·33; 95 % CI 1·24, 1·42). This association was driven by higher consumption of courgette and raw cucumber. Living with a partner was associated with higher odds of increasing consumption of fruits (OR=1·07; 95 % CI 1·02, 1·13) such as pear, peach and grape.Conclusions: Certain individual socio-economic factors, but none of the contextual socio-economic factors examined, were associated with an increase in F&V consumption. Factors associated with an increase in total F&V consumption were not necessarily associated with an increase in fruit or vegetable consumption separately, or with an increase in each subtype of fruit or vegetable. Magnitudes of the different associations observed also differed when F&V were considered together, separately or by subtype. Increases in F&V consumption were mostly observed in women with high socio-economic position. To develop effective nutritional interventions and policies that take the socio-economic environment of individuals into account, we recommend future research to further focus on (i) pathways through which population characteristics might influence changes in F&V consumption and (ii) existing interactions between individual and contextual socio-economic factors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: A balanced diet is essential to slowing the progression of chronic kidney disease (CKD) and managing the symptoms. Currently, no tool is available to easily and quickly assess energy and macronutrient intake in patients with non end-stage CKD. We aimed to develop and evaluate the validity and reproducibility of a new short 49-item food frequency questionnaire (SFFQ) adapted to patients with CKD.Methods: The CKD-REIN study is a prospective cohort that enrolled 3033 patients with moderate or advanced CKD from a national sample of nephrology clinics. A sub-sample of 201 patients completed the SFFQ twice, at a one-year interval and were included in the reproducibility study. During this interval, 127 patients also completed six 24-h recalls and were included in the validity study. Main nutrient and dietary intakes were computed. Validity was evaluated by calculating crude, energy-adjusted and de-attenuated correlation coefficients (CC) between FFQ and the mean of the 24-h recall results. Bland-Altman plots were performed and cross-classification into quintiles of consumption of each nutrient and food group was computed. Reproducibility between the two SFFQs was evaluated by intraclass CC (ICC).Results: Regarding validity, CC ranged from 0.05 to 0.79 (unadjusted CC, median: 0.40) and 0.10 to 0.59 (de-attenuated CC, median: 0.35) for food group and nutrient intakes, respectively. Five of the most important nutrients of interest in CKD, i.e. protein, calcium, phosphorus, potassium, and sodium had de-attenuated CC of 0.46, 0.43, 0.39, 0.32, and 0.12, respectively. The median of classification into the same or adjacent quintiles was 68% and 65% for food and nutrient intakes, respectively, and ranged from 63% to 69% for the five nutrients mentioned before. Bland-Altman plots showed good agreement across the range of intakes. ICC ranged from 0.18 to 0.66 (median: 0.46).Conclusions: The CKD-REIN SFFQ showed acceptable validity and reproducibility in a sample of patients with CKD, notably for CKD nutrients of importance. It can now be used in large-scale epidemiological studies to easily assess the relations between diet and CKD outcomes as well as in clinical routine. It may also serve as a basis for the development of FFQs in international CKD cohort networks. [ABSTRACT FROM AUTHOR]

Background: Incidence rates have increased considerably worldwide for both differentiated thyroid cancer and cutaneous melanoma, and two-way associations between these neoplasms have been described. Whether melanoma risk factors are associated with thyroid cancer risk remains unknown.Methods: Using Cox regression modeling, we prospectively analyzed the relationship between self-reported pigmentary traits, baseline residential ultraviolet (UV) exposure, and thyroid cancer risk in 86,960 women from the E3N cohort, followed-up over 1990-2008 through biennial questionnaires. We assessed associations of pigmentary traits and UV exposure with personal history of benign thyroid diseases using logistic regression modeling. All statistical tests were two sided.Results: In models adjusted for age and thyroid cancer risk factors, number of nevi was positively associated with thyroid cancer risk ("very many" vs. "none": hazards ratio [HR] = 1.7, 95% confidence interval [CI] = 1.0, 2.8; Ptrend = 0.01), independently of residential UV exposure or iodine intake. Risk was inversely associated with latitude and positively associated with mean daily UV level at baseline (HRs for the fourth vs. first quartile of latitude and spring/summer UVB level = 0.7, 95% CI = 0.5, 0.9; Ptrend = 0.03, and HR = 1.9, 95% CI = 1.4, 2.7; Ptrend = 0.02, respectively); associations were restricted to women with dietary iodine below the median intake. Number of nevi and UV level were also associated with personal histories of dysthyroidism and of goiter/nodules, although more weakly so.Conclusions: Our results suggest that number of nevi and residential UV exposure are associated with the risks of thyroid cancer and benign conditions. They point to novel pathways in thyroid cancer or melanoma etiologies and warrant replication. [ABSTRACT FROM AUTHOR]

Background: Differentiated thyroid cancer (TC) is the most common endocrine cancer. Fish can be an important source of iodine and other micronutrients and contaminants that may affect the thyroid gland and TC risk.Objective: We prospectively evaluated the relations between the consumption of total fish and different fish types and shellfish and TC risk in the EPIC (European Prospective Investigation into Cancer and Nutrition) study.Methods: EPIC is a cohort of >500,000 men and women, mostly aged 35-70 y, who were recruited in 10 European countries. After a mean follow-up of 14 y, 748 primary differentiated TC cases were diagnosed; 666 were in women and 601 were papillary TC. Data on intakes of lean fish, fatty fish, fish products, and shellfish were collected by using country-specific validated dietary questionnaires at recruitment. Multivariable Cox regression was used to calculate HRs and 95% CIs adjusted for many potential confounders, including dietary and nondietary factors.Results: No significant association was observed between total fish consumption and differentiated TC risk for the highest compared with the lowest quartile (HR: 1.03; 95% CI: 0.81, 1.32; P-trend = 0.67). Likewise, no significant association was observed with the intake of any specific type of fish, fish product, or shellfish. No significant heterogeneity was found by TC subtype (papillary or follicular tumors), by sex, or between countries with low and high TC incidence.Conclusion: This large study shows that the intake of fish and shellfish was not associated with differentiated TC risk in Europe, a region in which iodine deficiency or excess is rare. [ABSTRACT FROM AUTHOR]

Objective: To identify individual and contextual socio-economic factors associated with a healthy diet.Design: Dietary data from a large cohort study were used to derive two mutually exclusive dietary patterns through a latent class analysis. Associations between dietary patterns and socio-economic factors were studied with logistic regression.Setting: E3N, a French prospective cohort study composed of women recruited from a national health insurance plan covering people working in the national education system.Subjects: E3N participants (n 73 031) with dietary and socio-economic data available.Results: The 'Healthy' pattern was characterized by a large consumption of fruits and vegetables and the 'Less Healthy' pattern by a large consumption of pizza and processed meat. When all socio-economic factors were analysed together, all of the individual factors considered were associated with a healthy diet (e.g. women with three or more children were less likely to follow a healthy diet v. women with no children, OR (95 % CI): 0·70 (0·66, 0·75)) while the contextual factors associated with a healthy diet included the size of the agglomeration of residence and the area of birth and residence (e.g. women living in the West of France were less likely to follow a healthy diet v. those living in the South of France: 0·78 (0·72, 0·83)).Conclusions: We demonstrated that individual and contextual factors are both associated with diet. Rather than focusing only on individual factors, we recommend future studies or public health and nutritional strategies on diet to consider both types of factors. [ABSTRACT FROM AUTHOR]

Background: Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking.Methods: We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression.Results: Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70-81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses.Conclusions: These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Acrylamide was classified as 'probably carcinogenic' to humans in 1994 by the International Agency for Research on Cancer. In 2002, public health concern increased when acrylamide was identified in starchy, plant-based foods, processed at high temperatures. The purpose of this study was to identify which food groups and lifestyle variables were determinants of hemoglobin adduct concentrations of acrylamide (HbAA) and glycidamide (HbGA) in 801 non-smoking postmenopausal women from eight countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Biomarkers of internal exposure were measured in red blood cells (collected at baseline) by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) . In this cross-sectional analysis, four dependent variables were evaluated: HbAA, HbGA, sum of total adducts (HbAA + HbGA), and their ratio (HbGA/HbAA). Simple and multiple regression analyses were used to identify determinants of the four outcome variables. All dependent variables (except HbGA/HbAA) and all independent variables were log-transformed (log) to improve normality. Median (25th-75th percentile) HbAA and HbGA adduct levels were 41.3 (32.8-53.1) pmol/g Hb and 34.2 (25.4-46.9) pmol/g Hb, respectively. Results: The main food group determinants of HbAA, HbGA, and HbAA + HbGA were biscuits, crackers, and dry cakes. Alcohol intake and body mass index were identified as the principal determinants of HbGA/HbAA. The total percent variation in HbAA, HbGA, HbAA + HbGA, and HbGA/HbAA explained in this study was 30, 26, 29, and 13 %, respectively. Conclusions: Dietary and lifestyle factors explain a moderate proportion of acrylamide adduct variation in non-smoking postmenopausal women from the EPIC cohort. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The influence of artificial sweeteners on metabolic diseases is controversial. Artificially sweetened beverages have been associated with an increased risk of type 2 diabetes (T2D) but biases and reverse causation have been suspected to have influenced the observed association. In addition, it has been suggested that investigation into the relationship between the frequency and duration of the consumption of packet or tablet artificial sweeteners and T2D risk is necessary. Methods: We used data from 61,440 women in the prospective E3N-European Prospective Investigation into Cancer and Nutrition study, conducted between 1993 and 2011. We estimated hazards ratios (HRs) and 95% CIs of T2D risk associated with both the frequency and the duration of use of artificial sweeteners consumed in packets or tablets. Results: Compared to "never or rare" consumers of artificial sweeteners, those using them "always or almost always" had an increased risk of T2D (HR = 1.83 [95% CI 1.66-2.02] in the multivariate model [MM], HR = 1.33 [95% CI 1.201.47] when further adjusted for body mass index, BMI). Women consuming artificial sweeteners in packets or tablets for more than 10 years also had an increased risk of T2D compared to never or rare users (HR = 2.10 [95% CI 1.83-2.40] in the MM and HR = 1.15 [95% CI 1.00-1.33] when adjusted for BMI, respectively). Conclusions: Our data suggest that both a higher frequency and a longer consumption of artificial sweeteners in packets or tablets was associated with T2D risk, independently of major T2D risk factors, but partially mediated by adiposity. A precautionary principle should be applied to the promotion of these products that are still largely recommended as healthy sugar substitutes. [ABSTRACT FROM AUTHOR]

Background: The Mediterranean diet (MD) has been proposed as a means for cancer prevention, but little evidence has been accrued regarding its potential to prevent pancreatic cancer. We investigated the association between the adherence to the MD and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Methods: Over half a million participants from 10 European countries were followed up for over 11 years, after which 865 newly diagnosed exocrine pancreatic cancer cases were identified. Adherence to the MD was estimated through an adapted score without the alcohol component (arMED) to discount alcohol-related harmful effects. Cox proportional hazards regression models, stratified by age, sex and centre, and adjusted for energy intake, body mass index, smoking status, alcohol intake and diabetes status at recruitment, were used to estimate hazard ratios (HRs) associated with pancreatic cancer and their corresponding 95% confidence intervals (CIs).Results: Adherence to the arMED score was not associated with risk of pancreatic cancer (HR high vs low adherence=0.99; 95% CI: 0.77-1.26, and HR per increments of two units in adherence to arMED=1.00; 95% CI: 0.94-1.06). There was no convincing evidence for heterogeneity by smoking status, body mass index, diabetes or European region. There was also no evidence of significant associations in analyses involving microscopically confirmed cases, plausible reporters of energy intake or other definitions of the MD pattern.Conclusions: A high adherence to the MD is not associated with pancreatic cancer risk in the EPIC study. [ABSTRACT FROM AUTHOR]

Background: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers.Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk.Results: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, Ptrend=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, Ptrend=0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41-15.27, Ptrend=0.0135). For IHBC and GBTC, no significant associations were observed.Conclusions: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings. [ABSTRACT FROM AUTHOR]

Background: Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Circulating OPG and breast cancer risk has been examined in only one prior study.Methods: A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 2008 incident invasive breast cancer cases (estrogen receptor (ER)+, n = 1622; ER-, n = 386), matched 1:1 to controls, were included in the analysis. Women were predominantly postmenopausal at blood collection (77%); postmenopausal women included users and non-users of postmenopausal hormone therapy (HT). Serum OPG was quantified with an electrochemiluminescence assay. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression.Results: The associations between OPG and ER+ and ER- breast cancer differed significantly. Higher concentrations of OPG were associated with increased risk of ER- breast cancer (top vs. bottom tertile RR = 1.93 [95% CI 1.24-3.02]; p trend = 0.03). We observed a suggestive inverse association for ER+ disease overall and among women premenopausal at blood collection. Results for ER- disease did not differ by menopausal status at blood collection (p het = 0.97), and we observed no heterogeneity by HT use at blood collection (p het ≥ 0.43) or age at breast cancer diagnosis (p het ≥ 0.30).Conclusions: This study provides the first prospective data on OPG and breast cancer risk by hormone receptor subtype. High circulating OPG may represent a novel risk factor for ER- breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: Various food patterns have been associated with weight change in adults, but it is unknown which combinations of nutrients may account for such observations. We investigated associations between main nutrient patterns and prospective weight change in adults. Methods: This study includes 235,880 participants, 25-70 years old, recruited between 1992 and 2000 in 10 European countries. Intakes of 23 nutrients were estimated from country-specific validated dietary questionnaires using the harmonized EPIC Nutrient DataBase. Four nutrient patterns, explaining 67 % of the total variance of nutrient intakes, were previously identified from principal component analysis. Body weight was measured at recruitment and self-reported 5 years later. The relationship between nutrient patterns and annual weight change was examined separately for men and women using linear mixed models with random effect according to center controlling for confounders. Results: Mean weight gain was 460 g/year (SD 950) and 420 g/year (SD 940) for men and women, respectively. The annual differences in weight gain per one SD increase in the pattern scores were as follows: principal component (PC) 1, characterized by nutrients from plant food sources, was inversely associated with weight gain in men (−22 g/year; 95 % CI −33 to −10) and women (−18 g/year; 95 % CI −26 to −11). In contrast, PC4, characterized by protein, vitamin B2, phosphorus, and calcium, was associated with a weight gain of +41 g/year (95 % CI +2 to +80) and +88 g/year (95 % CI +36 to +140) in men and women, respectively. Associations with PC2, a pattern driven by many micro-nutrients, and with PC3, a pattern driven by vitamin D, were less consistent and/or non-significant. Conclusions: We identified two main nutrient patterns that are associated with moderate but significant long-term differences in weight gain in adults. [ABSTRACT FROM AUTHOR]

Background: The consumption of sweet beverages has been associated with greater risk of type 2 diabetes and obesity, which may be involved in the development of pancreatic cancer. Therefore, it has been hypothesized that sweet beverages may increase pancreatic cancer risk as well. Objective: We examined the association between sweet-beverage consumption (including total, sugar-sweetened, and artificially sweetened soft drink and juice and nectar consumption) and pancreatic cancer risk. Design: The study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. A total of 477,199 participants (70.2% women) with a mean age of 51 y at baseline were included, and 865 exocrine pancreatic cancers were diagnosed after a median follow-up of 11.60 y (IQR: 10.10-12.60 y). Sweet-beverage consumption was assessed with the use of validated dietary questionnaires at baseline. HRs and 95% CIs were obtained with the use of multivariable Cox regression models that were stratified by age, sex, and center and adjusted for educational level, physical activity, smoking status, and alcohol consumption. Associations with total soft-drink consumption were adjusted for juice and nectar consumption and vice versa. Results: Total soft-drink consumption (HR per 100 g/d: 1.03; 95% CI: 0.99, 1.07), sugar-sweetened soft-drink consumption (HR per 100 g/d: 1.02; 95% CI: 0.97, 1.08), and artificially sweetened soft-drink consumption (HR per 100 g/d: 1.04; 95% CI: 0.98, 1.10) were not associated with pancreatic cancer risk. Juice and nectar consumption was inversely associated with pancreatic cancer risk (HR per 100 g/d: 0.91; 95% CI: 0.84, 0.99); this association remained statistically significant after adjustment for body size, type 2 diabetes, and energy intake. Conclusions: Soft-drink consumption does not seem to be associated with pancreatic cancer risk. Juice and nectar consumption might be associated with a modest decreased pancreatic cancer risk. Additional studies with specific information on juice and nectar subtypes are warranted to clarify these results. [ABSTRACT FROM AUTHOR]

Background: Selenium status is suboptimal in many Europeans and may be a risk factor for the development of various cancers, including those of the liver and biliary tract. Objective: We wished to examine whether selenium status in advance of cancer onset is associated with hepatobiliary cancers in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Design: We assessed prediagnostic selenium status by measuring serum concentrations of selenium and selenoprotein P (SePP; the major circulating selenium transfer protein) and examined the association with hepatocellular carcinoma (HCC; n = 121), gallbladder and biliary tract cancers (GBTCs; n = 100), and intrahepatic bile duct cancer (IHBC; n = 40) risk in a nested case-control design within the EPIC study. Selenium was measured by total reflection X-ray fluorescence, and SePP was determined by a colorimetric sandwich ELISA. Multivariable ORs and 95% CIs were calculated by using conditional logistic regression. Results: HCC and GBTC cases, but not IHBC cases, showed significantly lower circulating selenium and SePP concentrations than their matched controls. Higher circulating selenium was associated with a significantly lower HCC risk (OR per 20-mg/L increase: 0.41; 95% CI: 0.23, 0.72) but not with the risk of GBTC or IHBC. Similarly, higher SePP concentrations were associated with lowered HCC risk only in both the categorical and continuous analyses (HCC: P-trend ≤ 0.0001; OR per 1.5-mg/L increase: 0.37; 95% CI: 0.21, 0.63). Conclusion: These findings from a large prospective cohort provide evidence that suboptimal selenium status in Europeans may be associated with an appreciably increased risk of HCC development. [ABSTRACT FROM AUTHOR]

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

The associations of body mass index (BMI) and other anthropometric measurements with lung cancer were examined in 348,108 participants in the European Investigation Into Cancer and Nutrition (EPIC) between 1992 and 2010. The study population included 2,400 case patients with incident lung cancer, and the average length of follow-up was 11 years. Hazard ratios were calculated using Cox proportional hazard models in which we modeled smoking variables with cubic splines. Overall, there was a significant inverse association between BMI (weight (kg)/height (m)²) and the risk of lung cancer after adjustment for smoking and other confounders (for BMI of 30.0-34.9 versus 18.5-25.0, hazard ratio = 0.72, 95% confidence interval: 0.62, 0.84). The strength of the association declined with increasing follow-up time. Conversely, after adjustment for BMI, waist circumference and waist-to-height ratio were significantly positively associated with lung cancer risk (for the highest category of waist circumference vs. the lowest, hazard ratio = 1.25, 95% confidence interval: 1.05, 1.50). Given the decline of the inverse association between BMI and lung cancer over time, the association is likely at least partly due to weight loss resulting from preclinical lung cancer that was present at baseline. Residual confounding by smoking could also have influenced our findings. [ABSTRACT FROM AUTHOR]

Background: Experimental and epidemiologic studies have yielded conflicting results on the relation between vitamin C intake and breast cancer risk. Objective: We investigated the relation between vitamin C supplement intake and breast cancer risk while considering dietary vitamin C intake. Design: Between 1995 and 2008, 2482 invasive breast cancer cases occurred in 57,403 postmenopausal women from the Etude Epidémiologique auprè s de femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective cohort during 581,085 person-years. We estimated vitamin C intake from foods with the use of a validated food-frequency questionnaire that was sent to subjects in 1993-1995 and vitamin C supplement use via questionnaires sent in 1995, 2000, 2002, and 2005. Multivariable HRs (95% CIs) for primary invasive breast cancer were estimated with the use of Cox regression models. All statistical tests were 2-sided. Results: Vitamin C supplement use (ever compared with never) was not associated with breast cancer risk overall; it was associated with higher breast cancer risk in women in the fourth quartile of vitamin C intake from foods (HR: 1.32; 95% CI: 1.04, 1.67) but not in other quartiles of dietary vitamin C intake (P-interaction = 0.03). Conclusions: We observed that vitamin C supplement use was associated with increased postmenopausal breast cancer risk in women with high vitamin C intake from foods. Our data suggest a potential U- or J-shaped relation between total vitamin C intake and postmenopausal breast cancer risk that deserves further investigation. [ABSTRACT FROM AUTHOR]