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.

Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. METHODS: In a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. FINDINGS: Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47-0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59-0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer. INTERPRETATION: Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations. FUNDING: World Cancer Research Fund (reference: 2013/1002); European Commission (FP7: BBMRI-LPC; reference: 313010).

Territorial gaps on quality of causes of death statistics over the last forty years in Spain.

BACKGROUND: The quality of the statistics on causes of death (CoD) does not present consolidated indicators in literature further than the coding group of ill-defined conditions of the International Classification of Diseases. Our objective was to assess the territorial quality of CoD by reliability of the official mortality statistics in Spain over the years 1980-2019. METHODS: A descriptive epidemiological design of four decades (1980-, 1990-, 2000-, and 2010-2019) by region (18) and sex was implemented. The CoD cases, age-adjusted rates and ratios (to all-cause) were assigned by reliability to unspecific and ill-defined quality categories. The regional mortality rates were contrasted to the Spanish median by decade and sex by the Comparative Mortality Ratio (CMR) in a Bayesian perspective. Statistical significance was considered when the CMR did not contain the value 1 in the 95% credible intervals. RESULTS: Unspecific, ill-defined, and all-cause rates by region and sex decreased over 1980-2019, although they scored higher in men than in women. The ratio of ill-defined CoD decreased in both sexes over these decades, but was still prominent in 4 regions. CMR of ill-defined CoD in both sexes exceeded the Spanish median in 3 regions in all decades. In the last decade, women's CMR significantly exceeded in 5 regions for ill-defined and in 6 regions for unspecific CoD, while men's CMR exceeded in 4 and 2 of the 18 regions, respectively on quality categories. CONCLUSIONS: The quality of mortality statistics of causes of death has increased over the 40 years in Spain in both sexes. Quality gaps still remain mostly in Southern regions. Authorities involved might consider to take action and upgrading regional and national death statistics, and developing a systematic medical post-grade training on death certification.

COVID-19, social determinants of transmission in the home. A population-based study.

BACKGROUND: Studying transmission within the home is essential to understand the transmission dynamics of numerous infectious diseases. For Coronavirus Disease-2019 (COVID-19), transmission within the home constitutes the majority exposure context. The risk of infection in this setting can be quantified by the household/intra-family secondary attack rate (SAR). In the literature, there are discrepancies in these values and little information about its social determinants. The aim of this study was to investigate transmission in the home by analyzing the influence of occupational social class, country of origin and gender/sex. METHODS: This was a retrospective cohort study of a population registry of cohabiting contacts with COVID-19 cases diagnosed from 15 June to 23 December 2020, in the Murcia Region. The household SAR was analyzed considering the characteristics of the primary case (sex, age, symptoms, occupational social class, country of origin and number of people in the household) and contact (age and sex) using a multilevel binary logistic regression model. RESULTS: Among the 37 727 contacts included, the intra-family SAR was 39.1%. The contacts of confirmed primary cases in the migrant population (Africa and Latin America) had higher attack rates, even after adjusting for the other variables. Older age and female sex were independent risk factors for contracting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) within the home. CONCLUSION: There was greater intra-domiciliary transmission among immigrants, likely related to the conditions of the home and situation of social vulnerability. Women were more likely to be infected by transmission from a cohabiting infected individual.

Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: Results from the European Prospective Investigation into Cancer and Nutrition study.

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine-Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HRQ4vsQ1 = 0.95, 95% CI: 0.73-1.23; Ptrend = .97; and HRper doubling of resistin concentration = 1.00; 95% CI: 0.84-1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

Breast cancer risk for the joint exposure to metals and metalloids in women: Results from the EPIC-Spain cohort.

Environmental factors play a role in breast cancer development. While metals and metalloids (MMs) include some carcinogens, their association with breast cancer depends on the element studied. Most studies focus on individual MMs, but the combined effects of metal mixtures remain unclear. The aim of this study was to analyze the relationship between the joint exposure to MMs and the risk of developing female breast cancer. We conducted a case-control study within the multicenter prospective EPIC-Spain cohort. Study population comprised 292 incident cases and 286 controls. Plasma concentrations of 16 MMs were quantified at recruitment. Potential confounders were collected using a questionnaire and anthropometric measurements. Mixed-effects logistic regression models were built to explore the effect of individual MMs. Quantile-based g computation models were applied to identify the main mixture components and to estimate the joint effect of the metal mixture. The geometric means were highest for Cu (845.6 ng/ml) and Zn (604.8 ng/ml). Cases had significantly higher Cu concentrations (p = 0.010) and significantly lower Zn concentrations (p < 0.001). Cu (+0.42) and Mn (+0.13) showed the highest positive weights, whereas Zn (-0.61) and W (-0.16) showed the highest negative weights. The joint effect of the metal mixture was estimated at an OR = 4.51 (95%CI = 2.32-8.79), suggesting a dose-response relationship. No evidence of non-linearity or non-additivity was found. An unfavorable exposure profile, primarily characterized by high Cu and low Zn levels, could lead to a significant increase in the risk of developing female breast cancer. Further studies are warranted to confirm these findings.

Relationship between exposure to parabens and benzophenones and prostate cancer risk in the EPIC-Spain cohort.

The etiology of prostate cancer is not fully elucidated. Among environmental risk factors, endocrine-disrupting chemicals (EDCs) deserve special mention, as they alter metabolic pathways involved in hormone-dependent cancers. Epidemiological evidence assessing the carcinogenicity of EDCs is scarce. The aim of this study was to analyze the relationship between exposure to parabens and benzophenones and prostate cancer risk. We conducted a case-cohort study nested within the EPIC-Spain prospective multi-center cohort. Study population comprised 1,838 sub-cohort participants and 467 non-sub-cohort prostate cancer cases. Serum concentrations of four parabens and two benzophenones were assessed at recruitment. Covariates included age, physical activity, tobacco smoking, alcohol consumption, body mass index, educational level and diabetes. Borgan II weighted Cox proportional hazard models stratified by study center were applied. Median follow-up time was 18.6 years (range = 1.0-21.7 years). Most sub-cohort participants reached primary education at most (65.5%), were overweight (57.7%) and had a low level of physical activity (51.3%). Detection percentages varied widely, being lowest for butyl-paraben (11.3%) and highest for methyl-paraben (80.7%), which also showed the highest geometric mean (0.95 ng/ml). Cases showed significantly higher concentrations of methyl-paraben (p = 0.041) and propyl-paraben (p < 0.001). In the multivariable analysis, methyl-paraben - log-transformed (HR = 1.07; 95%CI = 1.01-1.12) and categorized into tertiles (HR = 1.60 for T3; 95%CI = 1.16-2.20) -, butyl-paraben - linear (HR = 1.19; 95%CI = 1.14-1.23) and log-transformed (HR = 1.17; 95%CI = 1.01-1.35) - and total parabens - log-transformed (HR = 1.09; 95%CI = 1.02-1.17) and categorized into tertiles (HR = 1.62 for T3; 95%CI = 1.10-2.40) - were associated with an increased prostate cancer risk. In this study, higher concentrations of methyl-, butyl-, and total parabens were positively associated with prostate cancer risk. Further research is warranted to confirm these findings.

Body mass index and cancer risk among adults with and without cardiometabolic diseases: evidence from the EPIC and UK Biobank prospective cohort studies.

BACKGROUND: Whether cancer risk associated with a higher body mass index (BMI), a surrogate measure of adiposity, differs among adults with and without cardiovascular diseases (CVD) and/or type 2 diabetes (T2D) is unclear. The primary aim of this study was to evaluate separate and joint associations of BMI and CVD/T2D with the risk of cancer. METHODS: This is an individual participant data meta-analysis of two prospective cohort studies, the UK Biobank (UKB) and the European Prospective Investigation into Cancer and nutrition (EPIC), with a total of 577,343 adults, free of cancer, T2D, and CVD at recruitment. We used Cox proportional hazard regressions to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between BMI and incidence of obesity-related cancer and in turn overall cancer with a multiplicative interaction between BMI and the two cardiometabolic diseases (CMD). HRs and 95% CIs for separate and joint associations for categories of overweight/obesity and CMD status were estimated, and additive interaction was quantified through relative excess risk due to interaction (RERI). RESULTS: In the meta-analysis of both cohorts, BMI (per ~ 5 kg/m2) was positively associated with the risk of obesity-related cancer among participants without a CMD (HR: 1.11, 95%CI: 1.07,1.16), among participants with T2D (HR: 1.11, 95% CI: 1.05,1.18), among participants with CVD (HR: 1.17, 95% CI: 1.11,1.24), and suggestively positive among those with both T2D and CVD (HR: 1.09, 95% CI: 0.94,1.25). An additive interaction between obesity (BMI ≥ 30 kg/m2) and CVD with the risk of overall cancer translated into a meta-analytical RERI of 0.28 (95% CI: 0.09-0.47). CONCLUSIONS: Irrespective of CMD status, higher BMI increased the risk of obesity-related cancer among European adults. The additive interaction between obesity and CVD suggests that obesity prevention would translate into a greater cancer risk reduction among population groups with CVD than among the general population.

Prediagnostic Blood Metal Levels and the Risk of Parkinson's Disease: A Large European Prospective Cohort.

BACKGROUND: Metals have been postulated as environmental concerns in the etiology of Parkinson's disease (PD), but metal levels are typically measured after diagnosis, which might be subject to reverse causality. OBJECTIVE: The aim of this study was to investigate the association between prediagnostic blood metal levels and PD risk. METHODS: A case-control study was nested in a prospective European cohort, using erythrocyte samples collected before PD diagnosis. RESULTS: Most assessed metals were not associated with PD risk. Cadmium has a suggestive negative association with PD (odds ratio [95% confidence interval] for the highest quartile, 0.70 [0.42-1.17]), which diminished among never smokers. Among current smokers only, lead was associated with decreased PD risk (0.06 [0.01-0.35]), whereas arsenic showed associations toward an increased PD risk (1.85 [0.45-7.93]). CONCLUSIONS: We observe no strong evidence to support a role of metals in the development of PD. In particular, smoking may confound the association with tobacco-derived metals. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Incidence and time trends of childhood hematological neoplasms: a 36-year population-based study in the southern European context, 1983-2018.

Background: Hematological neoplasms (HNs) are the first and most common childhood cancers globally. Currently, there is a lack of updated population-based data on the incidence of these cancers in the Spanish pediatric population. This study aimed to describe the incidence and incidence trends of HNs in children (0-14 years) in Spain using data from the Spanish Network of Cancer Registries and to compare the results with other southern European countries. Methods: Data were extracted from 15 Spanish population-based cancer registries between 1983 and 2018. Cases were coded according to the International Classification of Diseases for Oncology, third edition, first revision, and grouped according to the International Classification of Childhood Cancer, third edition. Crude rates (CRs), age-specific rates, and age-standardized incidence rates using the 2013 European population (ASRE) were calculated and expressed as cases per 1,000,000 child-years. Incidence trends and annual percentage changes (APCs) were estimated. Results: A total of 4,747 HNs were recorded (59.5% boys). Age distribution [n (%)] was as follows: <1 year, 266 (5.6%); 1-4 years, 1,726 (36.4%); 5-9 years, 1,442 (30.4%); and 10-14 years, 1,313 (27.6%). Leukemias were the most common group, with a CR and an ASRE of 44.0 (95%CI: 42.5; 45.5) and 44.1 (95%CI: 42.6; 45.7), respectively. The CR and ASRE of lymphomas were 20.1 (95%CI: 19.1; 21.1) and 20.0 (95%CI: 19.0; 21.1), respectively. The comparable incidence rates between our results and those of other southern European countries were similar for lymphomas, while some differences were observed for leukemias. From 1988 to 2016, the trend in leukemia incidence was stable for both sexes, with an APC of 0.0 (95%CI: -0.5; 0.7), whereas a constant overall increase was observed for lymphoma in both sexes, with an APC of 1.0 (95%CI: 0.4; 1.6). Conclusion: Leukemias are the most common HNs in children, and their incidence has remained stable since 1988, whereas the incidence of lymphomas has increased every year. Lymphoma incidence is like that of other southern European countries, while leukemia incidence is similar only to that of southwestern European countries. Collaborative cancer registry projects allow for assessing epidemiological indicators for cancers such as HNs, which helps health authorities and clinicians provide more knowledge about these malignancies.

Lipopolysaccharide-binding protein and future Parkinson's disease risk: a European prospective cohort.

INTRODUCTION: Lipopolysaccharide (LPS) is the outer membrane component of Gram-negative bacteria. LPS-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by LPS and has been used as a blood marker for LPS. LBP has recently been indicated to be associated with Parkinson's disease (PD) in small-scale retrospective case-control studies. We aimed to investigate the association between LBP blood levels with PD risk in a nested case-control study within a large European prospective cohort. METHODS: A total of 352 incident PD cases (55% males) were identified and one control per case was selected, matched by age at recruitment, sex and study center. LBP levels in plasma collected at recruitment, which was on average 7.8 years before diagnosis of the cases, were analyzed by enzyme linked immunosorbent assay. Odds ratios (ORs) were estimated for one unit increase of the natural log of LBP levels and PD incidence by conditional logistic regression. RESULTS: Plasma LBP levels were higher in prospective PD cases compared to controls (median (interquartile range) 26.9 (18.1-41.0) vs. 24.7 (16.6-38.4) µg/ml). The OR for PD incidence per one unit increase of log LBP was elevated (1.46, 95% CI 0.98-2.19). This association was more pronounced among women (OR 2.68, 95% CI 1.40-5.13) and overweight/obese subjects (OR 1.54, 95% CI 1.09-2.18). CONCLUSION: The findings suggest that higher plasma LBP levels may be associated with an increased risk of PD and may thus pinpoint to a potential role of endotoxemia in the pathogenesis of PD, particularly in women and overweight/obese individuals.

Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel.

BACKGROUND: Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women. METHODS: We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel. RESULTS: In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28). CONCLUSIONS: Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women.

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.

A body shape index (ABSI) is associated inversely with post-menopausal progesterone-receptor-negative breast cancer risk in a large European cohort.

BACKGROUND: Associations of body shape with breast cancer risk, independent of body size, are unclear because waist and hip circumferences are correlated strongly positively with body mass index (BMI). METHODS: We evaluated body shape with the allometric "a body shape index" (ABSI) and hip index (HI), which compare waist and hip circumferences, correspondingly, among individuals with the same weight and height. We examined associations of ABSI, HI, and BMI (per one standard deviation increment) with breast cancer overall, and according to menopausal status at baseline, age at diagnosis, and oestrogen and progesterone receptor status (ER+/-PR+/-) in multivariable Cox proportional hazards models using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. RESULTS: During a mean follow-up of 14.0 years, 9011 incident breast cancers were diagnosed among 218,276 women. Although there was little evidence for association of ABSI with breast cancer overall (hazard ratio HR = 0.984; 95% confidence interval: 0.961-1.007), we found borderline inverse associations for post-menopausal women (HR = 0.971; 0.942-1.000; n = 5268 cases) and breast cancers diagnosed at age ≥ 55 years (HR = 0.976; 0.951-1.002; n = 7043) and clear inverse associations for ER + PR- subtypes (HR = 0.894; 0.822-0.971; n = 726) and ER-PR- subtypes (HR = 0.906; 0.835-0.983 n = 759). There were no material associations with HI. BMI was associated strongly positively with breast cancer overall (HR = 1.074; 1.049-1.098), for post-menopausal women (HR = 1.117; 1.085-1.150), for cancers diagnosed at age ≥ 55 years (HR = 1.104; 1.076-1.132), and for ER + PR + subtypes (HR = 1.122; 1.080-1.165; n = 3101), but not for PR- subtypes. CONCLUSIONS: In the EPIC cohort, abdominal obesity evaluated with ABSI was not associated with breast cancer risk overall but was associated inversely with the risk of post-menopausal PR- breast cancer. Our findings require validation in other cohorts and with a larger number of PR- breast cancer cases.

Association of Mediterranean diet with survival after breast cancer diagnosis in women from nine European countries: results from the EPIC cohort study.

BACKGROUND: The Mediterranean diet has been associated with lower risk of breast cancer (BC) but evidence from prospective studies on the role of Mediterranean diet on BC survival remains sparse and conflicting. We aimed to investigate whether adherence to Mediterranean diet prior to diagnosis is associated with overall and BC-specific mortality. METHODS: A total of 13,270 incident breast cancer cases were identified from an initial sample of 318,686 women in 9 countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Adherence to Mediterranean diet was estimated through the adapted relative Mediterranean diet (arMED), a 16-point score that includes 8 key components of the Mediterranean diet and excludes alcohol. The degree of adherence to arMED was classified as low (score 0-5), medium (score 6-8), and high (score 9-16). Multivariable Cox proportional hazards models were used to analyze the association between the arMED score and overall mortality, and Fine-Gray competing risks models were applied for BC-specific mortality. RESULTS: After a mean follow-up of 8.6 years from diagnosis, 2340 women died, including 1475 from breast cancer. Among all BC survivors, low compared to medium adherence to arMED score was associated with a 13% higher risk of all-cause mortality (HR 1.13, 95%CI 1.01-1.26). High compared to medium adherence to arMED showed a non-statistically significant association (HR 0.94; 95% CI 0.84-1.05). With no statistically significant departures from linearity, on a continuous scale, a 3-unit increase in the arMED score was associated with an 8% reduced risk of overall mortality (HR3-unit 0.92, 95% CI: 0.87-0.97). This result sustained when restricted to postmenopausal women and was stronger among metastatic BC cases (HR3-unit 0.81, 95% CI: 0.72-0.91). CONCLUSIONS: Consuming a Mediterranean diet before BC diagnosis may improve long-term prognosis, particularly after menopause and in cases of metastatic breast cancer. Well-designed dietary interventions are needed to confirm these findings and define specific dietary recommendations.

Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes: the EPIC-InterAct case-cohort study.

AIMS/HYPOTHESIS: Islet autoimmunity may progress to adult-onset diabetes. We investigated whether circulating odd-chain fatty acids (OCFA) 15:0 and 17:0, which are inversely associated with type 2 diabetes, interact with autoantibodies against GAD65 (GAD65Ab) on the incidence of adult-onset diabetes. METHODS: We used the European EPIC-InterAct case-cohort study including 11,124 incident adult-onset diabetes cases and a subcohort of 14,866 randomly selected individuals. Adjusted Prentice-weighted Cox regression estimated HRs and 95% CIs of diabetes in relation to 1 SD lower plasma phospholipid 15:0 and/or 17:0 concentrations or their main contributor, dairy intake, among GAD65Ab-negative and -positive individuals. Interactions between tertiles of OCFA and GAD65Ab status were estimated by proportion attributable to interaction (AP). RESULTS: Low concentrations of OCFA, particularly 17:0, were associated with a higher incidence of adult-onset diabetes in both GAD65Ab-negative (HR 1.55 [95% CI 1.48, 1.64]) and GAD65Ab-positive (HR 1.69 [95% CI 1.34, 2.13]) individuals. The combination of low 17:0 and high GAD65Ab positivity vs high 17:0 and GAD65Ab negativity conferred an HR of 7.51 (95% CI 4.83, 11.69), with evidence of additive interaction (AP 0.25 [95% CI 0.05, 0.45]). Low dairy intake was not associated with diabetes incidence in either GAD65Ab-negative (HR 0.98 [95% CI 0.94, 1.02]) or GAD65Ab-positive individuals (HR 0.97 [95% CI 0.79, 1.18]). CONCLUSIONS/INTERPRETATION: Low plasma phospholipid 17:0 concentrations may promote the progression from GAD65Ab positivity to adult-onset diabetes.

Associations between dietary inflammatory scores and biomarkers of inflammation in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BACKGROUND: Since the first version of the dietary inflammatory index (DII®) developed in the past decade, several other versions have been developed. However, to date no study has attempted to compare these versions with respect to their associations with biomarkers of inflammation. OBJECTIVE: We aimed to investigate the relationship between four dietary inflammatory scores [DII, two energy-adjusted derivatives (E-DII and E-DIIr), and the Inflammatory Score of the Diet (ISD)], and circulating levels of several inflammatory markers and adipokines. METHODS: This study included 17 637 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with at least one marker of inflammation measured in blood. Associations between the four scores and C-reactive protein (CRP), interleukin (IL)6, IL10, IL1RA, tumor necrosis factor-α (TNFα), soluble tumor necrosis factor receptor-1 (sTNFR1), sTNFR2, leptin, soluble leptin receptor (sLeptin R), adiponectin, and High Molecular Weight (HMW) adiponectin were evaluated using multivariable linear regressions adjusted for potential confounders. RESULTS: Positive associations were observed between the four dietary inflammatory scores and levels of CRP, IL6, sTNFR1, sTNFR2 and leptin. However, only the DII and the ISD were positively associated with IL1RA levels and only the DII and the E-DIIr were positively associated with TNFα levels. The proportion of variance of each biomarker explained by the scores was lower than 2%, which was equivalent to the variance explained by smoking status but much lower than that explained by body mass index. CONCLUSIONS: Our results suggest that the four dietary inflammatory scores were associated with some biomarkers of inflammation and could be used to assess the inflammatory potential of diet in European adults but are not sufficient to capture the inflammatory status of an individual. These findings can help to better understand the inflammatory potential of diet, but they need to be replicated in studies with repeated dietary measurements.

High adherence to Western dietary pattern and prostate cancer risk: findings from the EPIC-Spain cohort.

OBJECTIVE: To explore the association between three previously identified dietary patterns (Western, Prudent and Mediterranean) and prostate cancer (PCa) risk by tumour aggressiveness. SUBJECTS AND METHODS: The Spanish cohort of the European Prospective Investigation into Cancer and Nutrition study provided dietary and epidemiological information from 15 296 men recruited during the period 1992-1996. The associations between the adherence to the three dietary patterns and PCa risk (global, for Gleason grade groups 6 and >6, and for International Society of Urological Pathology [ISUP] grade 1 + 2 and ISUP grade 3 + 4 + 5) was explored with multivariable Cox proportional hazards regression models stratified by centre and age. RESULTS: While no effect on PCa risk was detected for the Prudent and Mediterranean dietary patterns, a suggestion of a detrimental effect of the Western dietary pattern was found (hazard ratio [HR]Q4vsQ1 1.29 [95% confidence interval {CI} 0.96;1.72]). This effect was only observed for Gleason grade group >6 (HRQ3vsQ1 1.61 [95% CI 1.00; 2.59] and HRQ4vsQ1 1.60 [95% CI 0.96; 2.67]) and in particular ISUP grade 3 + 4 + 5 tumours (HRQ2vsQ1 1.97 [95% CI 0.98; 3.93]; HRQ3vsQ1 2.72 (95% CI 1.35; 5.51); HRQ4vsQ1 2.29 [95% CI 1.07; 4.92]). CONCLUSIONS: Our results suggest that a high adherence to a healthy diet such as that represented by the Prudent and Mediterranean dietary patterns is not enough to prevent prostate cancer. Additionally, reducing adherence to a Western-type diet seems to be necessary.

Food processing and cancer risk in Europe: results from the prospective EPIC cohort study.

BACKGROUND: Food processing has been hypothesised to play a role in cancer development; however, data from large-scale epidemiological studies are scarce. This study investigated the association between dietary intake according to amount of food processing and risk of cancer at 25 anatomical sites using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: This study used data from the prospective EPIC cohort study, which recruited participants between March 18, 1991, and July 2, 2001, from 23 centres in ten European countries. Participant eligibility within each cohort was based on geographical or administrative boundaries. Participants were excluded if they had a cancer diagnosis before recruitment, had missing information for the NOVA food processing classification, or were within the top and bottom 1% for ratio of energy intake to energy requirement. Validated dietary questionnaires were used to obtain information on food and drink consumption. Participants with cancer were identified using cancer registries or during follow-up from a combination of sources, including cancer and pathology centres, health insurance records, and active follow-up of participants. We performed a substitution analysis to assess the effect of replacing 10% of processed foods and ultra-processed foods with 10% of minimally processed foods on cancer risk at 25 anatomical sites using Cox proportional hazard models. FINDINGS: 521 324 participants were recruited into EPIC, and 450 111 were included in this analysis (318 686 [70·8%] participants were female individuals and 131 425 [29·2%] were male individuals). In a multivariate model adjusted for sex, smoking, education, physical activity, height, and diabetes, a substitution of 10% of processed foods with an equal amount of minimally processed foods was associated with reduced risk of overall cancer (hazard ratio 0·96, 95% CI 0·95-0·97), head and neck cancers (0·80, 0·75-0·85), oesophageal squamous cell carcinoma (0·57, 0·51-0·64), colon cancer (0·88, 0·85-0·92), rectal cancer (0·90, 0·85-0·94), hepatocellular carcinoma (0·77, 0·68-0·87), and postmenopausal breast cancer (0·93, 0·90-0·97). The substitution of 10% of ultra-processed foods with 10% of minimally processed foods was associated with a reduced risk of head and neck cancers (0·80, 0·74-0·88), colon cancer (0·93, 0·89-0·97), and hepatocellular carcinoma (0·73, 0·62-0·86). Most of these associations remained significant when models were additionally adjusted for BMI, alcohol and dietary intake, and quality. INTERPRETATION: This study suggests that the replacement of processed and ultra-processed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types. FUNDING: Cancer Research UK, l'Institut National du Cancer, and World Cancer Research Fund International.