Nitrosyl-Heme and Heme Iron Intake from Processed Meats in Subjects from the EPIC-Spain Cohort.

BACKGROUND: The consumption of processed meats (PMs) and red meats are linked to the likelihood of developing colorectal cancer. Various theories have been proposed to explain this connection, focusing on nitrosyl-heme and heme iron intake. We hypothesized that differences in nitrosyl-heme and heme iron intakes will be associated with various sociodemographic and lifestyle factors. METHODS: The study included 38,471 healthy volunteers (62% females) from five Spanish regions within the EPIC-Spain cohort. High-Performance Liquid Chromatography (HPLC) determined nitrosyl-heme and heme iron levels in the 39 most consumed PMs. Food intake was assessed using validated questionnaires in interviews. Nitrosyl-heme and heme iron intakes, adjusted for sex, age, body mass index (BMI), center, and energy intake, were expressed as geometric means due to their skewed distribution. Variance analysis identified foods explaining the variability of nitrosyl-heme and heme iron intakes. RESULTS: The estimated intakes were 528.6 µg/day for nitrosyl-heme and 1676.2 µg/day for heme iron. Significant differences in nitrosyl-heme intake were found by sex, center, energy, and education level. Heme iron intake varied significantly by sex, center, energy, and smoking status. "Jamón serrano" and "jamón cocido/jamón de York" had the highest intake values, while "morcilla asturiana" and "sangrecilla" were key sources of nitrosyl-heme and heme iron. CONCLUSIONS: This is the first study to estimate levels of nitrosyl-heme intake directly in PMs for a large sample, revealing variations based on sex, BMI, smoking, and activity. Its data aids future exposure estimations in diverse populations.

Nitrosyl-heme and heme iron intake from processed meats and risk of colorectal cancer in the EPIC-Spain cohort.

BACKGROUND: The International Agency for Research on Cancer classified processed meats (PMs) as "carcinogenic" and red meat as "probably carcinogenic" for humans. The possible relationship between colorectal cancer (CRC) risk and the mechanisms involved in the carcinogenesis of PMs have not been established yet. Nitrosyl-heme and heme iron have been proposed as potential-related compounds. The aim of this study was to determine the association between nitrosyl-heme and heme iron intake and CRC risk among participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain study. METHODS: This prospective study included 38,262 men and women from the EPIC-Spain study. Food consumption was assessed using diet history and composition tables, with heme iron and nitrosyl-heme intake calculated from estimated PM item intakes and laboratory analyses. HR estimates were obtained by proportional hazard models, stratified by age at recruitment and study centre and adjusted for sex, total energy intake, education, smoking, body mass index, waist size, physical activity, lifetime alcohol, fibre, calcium and familiar CRC history. RESULTS: During a mean follow-up of 16.7years, 577 participants were diagnosed with CRC. We found no overall association between nitrosyl-heme (HRT3vsT1: 0.98 (95%IC: 0.79-1.21)) or heme iron intakes (HRT3vsT1: 0.88 (95%IC: 0.70-1.10)) with CRC risk, nor according to tumour subtypes. CONCLUSIONS: Our study found no evidence supporting a link between nitrosyl-heme or heme iron intake and CRC risk in Spanish subjects. IMPACT: As research on nitrosyl-heme is preliminary, more heterogeneous studies are necessary to provide more convincing evidence on their role in CRC carcinogenesis.

Associations between Fatty Acid Intakes and Plasma Phospholipid Fatty Acid Concentrations in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: The aim of this study is to determine the correlations between dietary fatty acid (FA) intakes and plasma phospholipid (PL) FA levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: The dietary intake of 60 individual FAs was estimated using centre-specific validated dietary questionnaires. Plasma PL FA concentrations of these FAs were measured in non-fasting venous plasma samples in nested case-control studies within the EPIC cohort (n = 4923, using only non-cases). Spearman rank correlations were calculated to determine associations between FA intakes and plasma PL FA levels. RESULTS: Correlations between FA intakes and circulating levels were low to moderately high (-0.233 and 0.554). Moderate positive correlations were found for total long-chain n-3 poly-unsaturated FA (PUFA) (r = 0.354) with the highest (r = 0.406) for n-3 PUFA docosahexaenoic acid (DHA). Moderate positive correlations were also found for the non-endogenously synthesized trans-FA (r = 0.461 for total trans-FA C16-18; r = 0.479 for industrial trans-FA (elaidic acid)). CONCLUSIONS: Our findings indicate that dietary FA intakes might influence the plasma PL FA status to a certain extent for several specific FAs. The stronger positive correlations for health-enhancing long-chain PUFAs and the health-deteriorating trans-FA that are not endogenously produced are valuable for future cancer prevention public health interventions.

Reproductive and hormonal factors and risk of renal cell carcinoma among women in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology. MATERIALS & METHODS: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. RESULTS: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use. CONCLUSION: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.

Breakfast Size and Prevalence of Metabolic Syndrome in the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish Cohort.

BACKGROUND: Recent evidence suggest that energy distribution during the daytimecould be a potential determinant for the development of metabolic syndrome (MetS). OBJECTIVE: To cross-sectionally assess the association between breakfast size and the prevalence of MetS in Spanish adults. METHODS: Our study included a subset of 3644 participants from the European Prospective Investigation into Cancer and Nutrition Spain study recontacted between 2017-2018. Information on diet, sociodemographic, lifestyle, sleep quality, and chronotype was collected using standardized questionnaires, while anthropometric and blood pressure data were measured in a face-to-face personal interview by a nurse. MetS was defined according to the Adult Treatment Panel III (ATPIII) definition by measuring serum levels of total cholesterol, tryglycerides and glucose. Breakfast size was calculated as: (energy from breakfast/total energy intake) * 2000 kcal. To evaluate the association between breakfast size and MetS prevalence, a multivariable logistic regression model adjusted by potential confounders was used to estimate OR and 95% CI. RESULTS: Prevalence of MetS in our study was 40.7%. The mean breakfast size was 306.6 * 2000 kcal (15% of the total daily energy intake), with 14 (0.4%) participants skipping breakfast. Participants in the highest quartile of breakfast size had a lower MetS prevalence compared to participants in the lowest quartile (ORQ4vsQ1 = 0.62; 95% CI = 0.51-0.76; p-trend < 0.001). No modification of the estimated ORs by sex, breakfast time, and number of eating occasions per day were observed. CONCLUSION: Our results suggest that higher breakfast size is associated with lower prevalence of MetS in Spanish adults, supporting the importance of a high energy breakfast. Further prospective studies are necessary to confirm these findings.

Mycotoxin Exposure and Renal Cell Carcinoma Risk: An Association Study in the EPIC European Cohort.

BACKGROUND: Mycotoxins have been suggested to contribute to a spectrum of adverse health effects in humans, including at low concentrations. The recognition of these food contaminants being carcinogenic, as co-occurring rather than as singularly present, has emerged from recent research. The aim of this study was to assess the potential associations of single and multiple mycotoxin exposures with renal cell carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Food questionnaire data from the EPIC cohort were matched to mycotoxin food occurrence data compiled by the European Food Safety Authority (EFSA) from European Member States to assess long-term dietary mycotoxin exposures, and to associate these with the risk of renal cell carcinoma (RCC, n = 911 cases) in 450,112 EPIC participants. Potential confounding factors were taken into account. Analyses were conducted using Cox's proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs) with mycotoxin exposures expressed as µg/kg body weight/day. RESULTS: Demographic characteristics differed between the RCC cases and non-cases for body mass index, age, alcohol intake at recruitment, and other dietary factors. In addition, the mycotoxin exposure distributions showed that a large proportion of the EPIC population was exposed to some of the main mycotoxins present in European foods such as deoxynivalenol (DON) and derivatives, fumonisins, Fusarium toxins, Alternaria toxins, and total mycotoxins. Nevertheless, no statistically significant associations were observed between the studied mycotoxins and mycotoxin groups, and the risk of RCC development. CONCLUSIONS: These results show an absence of statistically significant associations between long-term dietary mycotoxin exposures and RCC risk. However, these results need to be validated in other cohorts and preferably using repeated dietary exposure measurements. In addition, more occurrence data of, e.g., citrinin and fumonisins in different food commodities and countries in the EFSA database are a prerequisite to establish a greater degree of certainty.

Circadian clock gene variants and their link with chronotype, chrononutrition, sleeping patterns and obesity in the European prospective investigation into cancer and nutrition (EPIC) study.

BACKGROUND & AIMS: The circadian clock is involved in the control of daily rhythms and is related to the individual's chronotype, i.e., the morningness-eveneningness preference. Knowledge is limited on the relationship between circadian genes, chronotype, sleeping patterns, chronutrition and obesity. The aim was to explore these associations within the EPIC-Spain cohort study. METHODS: There were 3183 subjects with information on twelve genetic variants of six genes (PER1, PER2, PER3, CRY1, NR1D1, CLOCK). Their association was evaluated with: chronotype and sleeping duration/quality (assessed by questionnaires), chrononutrition (number of meals and timing of intake assessed by a diet history), and also anthropometric measures of obesity at early and late adulthood (in two points in time), such as weight and waist circumference (assessed by physical measurements). Multivariable logistic and linear regression as well as additive genetic models were applied. Odds ratios (ORs), ß coefficients, and p-values corrected for multiple comparisons were estimated. Genetic risk scores (GRS) were built to test gene-outcome associations further. RESULTS: At nominal significance level, the variant rs2735611 (PER1 gene) was associated with a 11.6% decrease in long-term weight gain (per-allele ß = -0.12), whereas three CLOCK gene variants (rs12649507, rs3749474 and rs4864548), were associated with a ∼20% decrease in waist circumference gain (per-allele ߠ∼ -0.19). These and other associations with body measures did not hold after multiple testing correction, except waist-to-hip ratio and rs1801260, rs2070062 and rs4580704 (CLOCK gene). Associations with chrononutrition variables, chronotype and sleep duration/quality failed to reach statistical significance. Conversely, a weighted GRS was associated with the evening/late chronotype and with all other outcomes (p < 0.05). The chronotype-GRS was associated with an increased overweight/obesity risk (vs normal weight) in both early and late adulthood (OR = 2.2; p = 0.004, and OR = 2.1; p = 0.02, respectively). CONCLUSION: Genetic variants of some circadian clock genes could explain the link between genetic susceptibility to the individual's chronotype and obesity risk.

Pre-pregnancy overweight and obesity prevalence and relation to maternal and perinatal outcomes.

OBJECTIVE: To identify the prevalence of pre-pregnancy overweight/obesity in pregnant women and its relationship with socio-demographic factors and to describe the maternal and perinatal outcomes in a Barcelona hospital (Spain). METHOD: A descriptive cross-association study, with retrospective data collection, was performed Barcelona Hospital. The data of 5447 pregnant women who delivered at >=23 weeks of gestation were included. Body Mass Index (BMI) data were categorised into World Health Organization classifications. p values <.05 (two-tailed) were considered significant. Logistic regression models were performed. RESULTS: The prevalence of pre-pregnancy obesity was 8.4% and 18.9% for overweight. Gestational diabetes was more frequent in pre-pregnancy overweight/obesity (OR 1.92: 95% CI 1.54-2.40 and OR 3.34: 95% CI 2.57-4.33), as were preeclampsia (OR 2.08: 95% CI 1.55-2.79 and OR 3.35: 95% CI 2.38-4.71), induction of labour (OR 1.19: 95% CI 1.02-1.38 and OR 1.94: 95% CI 1.57-2.10), caesarean section (OR 1.41: 95% CI 1.21-1.65 and OR 2.68: 95% CI 2.18-3.29), prematurity (OR 1.28: 95% CI 1-1.65 and OR 1.79: 95% CI 1.32-2.44) and macrosomia (OR 1.87: 95% CI 1.43-2.46 and OR 2.03: 95% CI 1.40-2.93). CONCLUSIONS: One in four pregnant women had pre-pregnancy overweight or obesity. This study shows the relationship between pre-pregnancy overweight or obesity with adverse maternal and perinatal outcomes.

Effectiveness of a Step Counter Smartband and Midwife Counseling Intervention on Gestational Weight Gain and Physical Activity in Pregnant Women With Obesity (Pas and Pes Study): Randomized Controlled Trial.

BACKGROUND: Women who are pregnant and have obesity and excessive gestational weight gain (GWG) present a higher risk of maternal and perinatal complications. The use of mobile apps and a wristband during pregnancy may contribute to promoting healthy lifestyles and, thus, improving maternal and neonatal health. OBJECTIVE: This study aims to evaluate the effectiveness of a complex digital health intervention, using a smartband and app with midwife counseling, on GWG and physical activity (PA) in women who are pregnant and have obesity and analyze its impact on maternal and perinatal outcomes. In addition, we aim to study the frequency of use, usability, and satisfaction with the mobile apps used by the women in the intervention group. METHODS: A parallel, 2-arm, randomized controlled trial was conducted. A total of 150 women who were pregnant and had obesity were included. The intervention group received a complex combined digital intervention. The intervention was delivered with a smartband (Mi Band 2) linked to the app Mi Fit to measure PA and the Hangouts app with the midwife to provide personal health information. The control group received usual care. The validated Spanish versions of the International Physical Activity Questionnaire-Short Form and the System Usability Scale were used. Satisfaction was measured on a 1- to 5-point Likert scale. RESULTS: We analyzed 120 women, of whom 30 (25%) were withdrawn because of the COVID-19 pandemic. The median GWG in the intervention group was 7.0 (IQR 4-11) kg versus 9.3 (IQR 5.9-13.3) kg in the control group (P=.04). The adjusted mean GWG per week was 0.5 (95% CI 0.4-0.6) kg per week in the control group and 0.3 (95% CI 0.3-0.4) kg per week in the intervention group (df=0.1, 95% CI -0.2 to 0.03; P=.008). During the 35 and 37 gestational weeks, women in the intervention group had higher mean PA than women in the control group (1980 metabolic equivalents of tasks-minutes per week vs 1386 metabolic equivalents of tasks-minutes per week, respectively; P=.01). No differences were observed between the study groups in the incidence of maternal and perinatal outcomes. In the intervention group, 61% (36/59) of the women who were pregnant used the smartband daily, and 75% (44/59) evaluated the usability of the Mi Fit app as excellent. All women in the intervention group used the Hangouts app at least once a week. The mean of the satisfaction scale with the health counseling app and midwife support was 4.8/5 (SD 0.6) points. CONCLUSIONS: The use of a complex mobile health intervention was associated with adequate GWG, which was lower in the intervention group than in the control group. In addition, we observed that the intervention group had increases in PA. No differences were observed in maternal perinatal complications. TRIAL REGISTRATION: ClinicalTrials.gov NCT03706872; https://www.clinicaltrials.gov/ct2/show/NCT03706872.

Efectividad de una intervención digital compleja en los hábitos alimentarios de gestantes con obesidad preconcepcional / Effectiveness of a complex digital intervention on eating habits in pregnant women with pre-pregnancy obesity

Objetivo: Evaluar la efectividad de una intervención digital compleja, en gestantes con obesidad, con la provisión de consejos sobre hábitos alimentarios y el soporte virtual de una matrona a través de una app, respecto a los hábitos alimentarios, así como analizar el grado de satisfacción global con la intervención digital. Métodos: Se realizó un ensayo clínico paralelo aleatorizado con dos brazos 1:1 con grupo intervención (GI) y grupo control (GC). Se incluyeron 150 gestantes con obesidad preconcepcional. Ambos grupos recibieron el control prenatal habitual. La intervención en el GI fue el uso de una pulsera de actividad y la recepción de consejos sobre hábitos alimentarios mediante una app, y el soporte virtual de una matrona. Se utilizó el «Cuestionario de hábitos alimentarios para pacientes con sobrepeso y obesidad» en una escala Likert de 1 a 5. Las pruebas estadísticas fueron bilaterales y se evaluaron a un nivel α de 0,05. Los análisis se realizaron con SPSS v. 25 y SAS v. 9.4.Resultados: Se analizaron 110 (73,3 % del total) mujeres. En el GI la puntuación media de los hábitos alimentarios fue mayor que en el GC (3,49 ± 0,36 vs. 3,35 ± 0,41; p= 0,056), pero no se observaron diferencias estadísticamente significativas. En el GI, la puntuación media del consumo del tipo de alimentos fue mayor que en el GC (3,49 ± 0,78 vs. 3,18 ± 0,71; p= 0,019). El grado de satisfacción global fue de 4,76 ± 0,6 puntos de media. Conclusiones: El uso de una intervención digital compleja fue efectivo en la mejora del consumo del tipo de alimentos respecto a las gestantes que solo recibieron el control prenatal habitual. (AU)

Objective: To assess the effectiveness of a complex digital health intervention, in pregnant women with obesity, by means of an app for advice eating habits and a virtual midwife’s support, regarding their eating habits, and also to analyze the global satisfaction with digital intervention.Methods: A parallel randomized clinical trial with two arms 1:1 with intervention group (IG) and control group (CG) was conducted. 150 pregnant women with pre-pregnancy obesity were included. Both groups received usual prenatal care. The intervention, in the IG, was delivered with smartband and an app providing advice about eating habits and with a virtual midwife to support women. The validated «Questionnaire of eating habits for patients with overweight and obesity» was administrated and measured using a 1-to-5-point Likert scale. Statistical tests were two-sided and evaluated at an α level of 0.05. Analyzes were performed with SPSS v. 25 and SAS v. 9.4.Results: 110 (73.3% of the total) women were analyzed. In the IG, the mean score for eating habits was higher than in the CG (3.49 ± 0.36 versus 3.35 ± 0.41; p=0.056), but no statistically significant differences were observed. In the IG, the mean score for the intake of the type of food was higher than in the CG (3.49 ± 0.78 versus 3.18 ± 0.71; p=0.019). The mean of global satisfaction was 4.76 ± 0.6 points. Conclusions: The use of a complex digital intervention was effective in improving the intake of the type of food compared to pregnant women who only received usual prenatal care. (AU)

Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: Nε-carboxy-methyllysine (CML), Nε-carboxyethyllysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HRQ5vs.Q1 = 0.92, 95% CI = 0.85-1.00) and MG-H1 (HRQ5vs.Q1 = 0.92, 95% CI = 0.85-1.00), but not for CEL (HRQ5vs.Q1 = 0.97, 95% CI = 0.89-1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.

Pre-pregnancy overweight and obesity prevalence and relation to maternal and perinatal outcomes.

OBJECTIVE: To identify the prevalence of pre-pregnancy overweight/obesity in pregnant women and its relationship with socio-demographic factors and to describe the maternal and perinatal outcomes in a Barcelona hospital (Spain). METHOD: A descriptive cross-association study, with retrospective data collection, was performed Barcelona Hospital. The data of 5447 pregnant women who delivered at >=23 weeks of gestation were included. Body Mass Index (BMI) data were categorised into World Health Organization classifications. p values <.05 (two-tailed) were considered significant. Logistic regression models were performed. RESULTS: The prevalence of pre-pregnancy obesity was 8.4% and 18.9% for overweight. Gestational diabetes was more frequent in pre-pregnancy overweight/obesity (OR 1.92: 95% CI 1.54-2.40 and OR 3.34: 95% CI 2.57-4.33), as were preeclampsia (OR 2.08: 95% CI 1.55-2.79 and OR 3.35: 95% CI 2.38-4.71), induction of labour (OR 1.19: 95% CI 1.02-1.38 and OR 1.94: 95% CI 1.57-2.10), caesarean section (OR 1.41: 95% CI 1.21-1.65 and OR 2.68: 95% CI 2.18-3.29), prematurity (OR 1.28: 95% CI 1-1.65 and OR 1.79: 95% CI 1.32-2.44) and macrosomia (OR 1.87: 95% CI 1.43-2.46 and OR 2.03: 95% CI 1.40-2.93). CONCLUSIONS: One in four pregnant women had pre-pregnancy overweight or obesity. This study shows the relationship between pre-pregnancy overweight or obesity with adverse maternal and perinatal outcomes.

Associations between dietary amino acid intakes and blood concentration levels.

BACKGROUND AND AIMS: Emerging evidence suggests a role of amino acids (AAs) in the development of various diseases including renal failure, liver cirrhosis, diabetes and cancer. However, mechanistic pathways and the effects of dietary AA intakes on circulating levels and disease outcomes are unclear. We aimed to compare protein and AA intakes, with their respective blood concentrations in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Dietary protein and AA intakes were assessed via the EPIC dietary questionnaires (DQ) and 24-h dietary recalls (24-HDR). A subsample of 3768 EPIC participants who were free of cancer had blood AA concentrations measured. To investigate how circulating levels relate to their respective intakes, dietary AA intake was examined in quintiles and ANOVA tests were run. Pearson correlations were examined for continous associations between intakes and blood concentrations. RESULTS: Dietary AA intakes (assessed with the DQ) and blood AA concentrations were not strongly correlated (-0.15 ≤ r ≤ 0.17) and the direction of the correlations depended on AA class: weak positive correlations were found for most essential AAs (isoleucine, leucine, lysine, methionine, threonine, tryptophan, and valine) and conditionally essential AAs (arginine and tyrosine), while negative associations were found for non-essential AAs. Similar results were found when using the 24-HDR. When conducting ANOVA tests for essential AAs, higher intake quintiles were linked to higher blood AA concentrations, except for histidine and phenylalanine. For non-essential AAs and glycine, an inverse relationship was observed. Conditionally-essential AAs showed mixed results. CONCLUSIONS: Weak positive correlations and dose responses were found between most essential and conditionally essential AA intakes, and blood concentrations, but not for the non-essential AAs. These results suggest that intake of dietary AA might be related to physiological AA status, particularly for the essential AAs. However, these results should be further evaluated and confirmed in large-scale prospective studies.

Soft Drink and Juice Consumption and Renal Cell Carcinoma Incidence and Mortality in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Renal cell carcinoma (RCC) accounts for more than 80% of kidney cancers in adults, and obesity is a known risk factor. Regular consumption of sweetened beverages has been linked to obesity and several chronic diseases, including some types of cancer. It is uncertain whether soft drink and juice consumption is associated with risk of RCC. We investigated the associations of soft drink and juice consumption with RCC incidence and mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: A total of 389,220 EPIC participants with median age of 52 years at recruitment (1991-2000) were included. Cox regression yielded adjusted HRs and 95% confidence intervals (CI) for RCC incidence and mortality in relation to intakes of juices and total, sugar-sweetened, and artificially sweetened soft drinks. RESULTS: A total of 888 incident RCCs and 356 RCC deaths were identified. In models including adjustment for body mass index and energy intake, there was no higher risk of incident RCC associated with consumption of juices (HR per 100 g/day increment = 1.03; 95% CI, 0.97-1.09), total soft drinks (HR = 1.01; 95% CI, 0.98-1.05), sugar-sweetened soft drinks (HR = 0.99; 95% CI, 0.94-1.05), or artificially sweetened soft drinks (HR = 1.02; 95% CI, 0.96-1.08). In these fully adjusted models, none of the beverages was associated with RCC mortality (HR, 95% CI per 100 g/day increment 1.06, 0.97-1.16; 1.03, 0.98-1.09; 0.97, 0.89-1.07; and 1.06, 0.99-1.14, respectively). CONCLUSIONS: Consumption of juices or soft drinks was not associated with RCC incidence or mortality after adjusting for obesity. IMPACT: Soft drink and juice intakes are unlikely to play an independent role in RCC development or mortality.

A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

BACKGROUND: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health. OBJECTIVES: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics. MEDTHODS: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP. RESULTS: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers. CONCLUSIONS: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors.

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

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

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

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.

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

BACKGROUND: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. METHODS: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non-muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models. RESULTS: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 = 0.48; 0.25-0.90; P trend in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03-1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non-muscle-invasive urothelial carcinoma risk was observed. CONCLUSIONS: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk. IMPACT: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.

Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition.

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992-2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00-1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97-1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.

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

Four epidemiologic studies have assessed the association between nut intake and pancreatic cancer risk with contradictory results. The present study aims to investigate the relation between nut intake (including seeds) and pancreatic ductal adenocarcinoma (PDAC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to estimate hazards ratio (HR) and 95% confidence intervals (95% CI) for nut intake and PDAC risk. Information on intake of nuts was obtained from the EPIC country-specific dietary questionnaires. After a mean follow-up of 14 years, 476,160 participants were eligible for the present study and included 1,283 PDAC cases. No association was observed between consumption of nuts and PDAC risk (highest intake vs nonconsumers: HR, 0.89; 95% CI, 0.72-1.10; p-trend = 0.70). Furthermore, no evidence for effect-measure modification was observed when different subgroups were analyzed. Overall, in EPIC, the highest intake of nuts was not statistically significantly associated with PDAC risk.