Publications by authors named "Aurelio Barricarte"

318 Publications

HIGH-RISK SUBTYPES OF CHRONIC LYMPHOCYTIC LEUKEMIA ARE DETECTABLE AS EARLY AS 16 YEARS PRIOR TO DIAGNOSIS.

Blood 2021 Oct 18. Epub 2021 Oct 18.

Erasmus MC, Rotterdam, Netherlands.

Chronic lymphocytic leukemia (CLL) is preceded by monoclonal B-cell lymphocytosis (MBL), a CLL precursor state with a prevalence of up to 12% in aged individuals. However, the duration of MBL and the mechanisms of its evolution to CLL remain largely unknown. In this study, we sequenced the B-cell receptor immunoglobulin heavy chain (BcR IGH) gene repertoire of 124 CLL patients and 118 matched controls in blood samples taken up to 22 years prior to diagnosis. Significant skewing in the BcR IGH gene repertoire was detected in the majority of patients, even before the occurrence of lymphocytosis and irrespective of the clonotypic IGH variable gene somatic hypermutation status. Furthermore, in 14 CLL patients we identified dominant clonotypes belonging to major stereotyped subsets associated with poor prognosis up to 16 years before diagnosis. In 22 patients with longitudinal samples, the skewing of the BcR IGH gene repertoire increased significantly over time to diagnosis or remained stable at high levels. For 14/16 patients with available samples at diagnosis, the CLL clonotype was already present in the pre-diagnostic samples. Overall, our data indicate that the pre-clinical phase of CLL could be longer than previously thought, even in adverse-prognostic cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2021012890DOI Listing
October 2021

Consumption of ultra-processed foods associated with weight gain and obesity in adults: A multi-national cohort study.

Clin Nutr 2021 09 21;40(9):5079-5088. Epub 2021 Aug 21.

Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Background: There is a worldwide shift towards increased consumption of ultra-processed foods (UPF) with concurrent rising prevalence of obesity. We examined the relationship between the consumption of UPF and weight gain and risk of obesity.

Methods: This prospective cohort included 348 748 men and women aged 25-70 years. Participants were recruited between 1992 and 2000 from 9 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Two body weight measures were available, at baseline and after a median follow-up time of 5 years. Foods and drinks were assessed at baseline by dietary questionnaires and classified according to their degree of processing using NOVA classification. Multilevel mixed linear regression was used to estimate the association between UPF consumption and body weight change (kg/5 years). To estimate the relative risk of becoming overweight or obese after 5 years we used Poisson regression stratified according to baseline body mass index (BMI).

Results: After multivariable adjustment, higher UPF consumption (per 1 SD increment) was positively associated with weight gain (0·12 kg/5 years, 95% CI 0·09 to 0·15). Comparing highest vs. lowest quintile of UPF consumption was associated with a 15% greater risk (95% CI 1·11, 1·19) of becoming overweight or obese in normal weight participants, and with a 16% greater risk (95% CI 1·09, 1·23) of becoming obese in participants who were overweight at baseline.

Conclusions: These results are supportive of public health campaigns to substitute UPF for less processed alternatives for obesity prevention and weight management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clnu.2021.08.009DOI Listing
September 2021

Polyphenol Intake and Epithelial Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

Antioxidants (Basel) 2021 Aug 4;10(8). Epub 2021 Aug 4.

Institut Gustave Roussy, 94805 Villejuif, France.

Despite some epidemiological evidence on the protective effects of polyphenol intake on epithelial ovarian cancer (EOC) risk from case-control studies, the evidence is scarce from prospective studies and non-existent for several polyphenol classes. Therefore, we aimed to investigate the associations between the intake of total, classes and subclasses of polyphenols and EOC risk in a large prospective study. The study was conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which included 309,129 adult women recruited mostly from the general population. Polyphenol intake was assessed through validated country-specific dietary questionnaires and the Phenol-Explorer database. During a mean follow-up of 14 years, 1469 first incident EOC cases (including 806 serous, 129 endometrioid, 102 mucinous, and 67 clear cell tumours) were identified. In multivariable-adjusted Cox regression models, the hazard ratio in the highest quartile of total polyphenol intake compared with the lowest quartile (HR) was 1.14 (95% CI 0.94-1.39; -trend = 0.11). Similarly, the intake of most classes and subclasses of polyphenols were not related to either overall EOC risk or any EOC subtype. A borderline statistically significant positive association was observed between phenolic acid intake (HR = 1.20, 95% CI 1.01-1.43; -trend = 0.02) and EOC risk, especially for the serous subtype and in women with obesity, although these associations did not exceed the Bonferroni correction threshold. The current results do not support any association between polyphenol intake and EOC in our large European prospective study. Results regarding phenolic acid intake need further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox10081249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389235PMC
August 2021

Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.

Cancer Epidemiol Biomarkers Prev 2021 01 3;30(1):217-228. Epub 2020 Nov 3.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.

Methods: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data.

Results: Genetic correlation analysis revealed significant genetic correlation between the two cancers ( = 0.43, = 2.66 × 10). We found seven loci associated with risk for both cancers ( < 2.4 × 10). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified ( < 5 × 10). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation.

Conclusions: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis.

Impact: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-0739DOI Listing
January 2021

Association between anthropometry and lifestyle factors and risk of B-cell lymphoma: An exposome-wide analysis.

Int J Cancer 2021 05 12;148(9):2115-2128. Epub 2020 Nov 12.

Department of Oncology, Lund University, Lund, Sweden.

To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single-study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048490PMC
May 2021

Blood Metal Levels and Amyotrophic Lateral Sclerosis Risk: A Prospective Cohort.

Ann Neurol 2021 01 6;89(1):125-133. Epub 2020 Nov 6.

Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.

Objective: Metals have been suggested as a risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies are available to date. We compared metal levels in prospectively collected blood samples from ALS patients and controls, to explore whether metals are associated with ALS mortality.

Methods: A nested ALS case-control study was conducted within the prospective EPIC (European Prospective Investigation into Cancer and Nutrition) cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as a biomarker for metal exposure from any source. Arsenic, cadmium, copper, lead, manganese, mercury, selenium, and zinc concentrations were measured by inductively coupled plasma-mass spectrometry. To estimate ALS risk, we applied conditional logistic regression models.

Results: The study population comprised 107 cases (65% female) and 319 controls matched for age, sex, and study center. Median time between blood collection and ALS death was 8 years (range = 1-15). Comparing the highest with the lowest tertile, cadmium (odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.08-3.87) and lead (OR = 1.89, 95% CI = 0.97-3.67) concentrations suggest associations with increased ALS risk. Zinc was associated with a decreased risk (OR = 0.50, 95% CI = 0.27-0.94). Associations for cadmium and lead remained when limiting analyses to noncurrent smokers.

Interpretation: This is the first study to compare metal levels before disease onset, minimizing reverse causation. The observed associations suggest that cadmium, lead, and zinc may play a role in ALS etiology. Cadmium and lead possibly act as intermediates on the pathway from smoking to ALS. ANN NEUROL 20209999:n/a-n/a.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756568PMC
January 2021

Greenhouse gases emissions from the diet and risk of death and chronic diseases in the EPIC-Spain cohort.

Eur J Public Health 2021 02;31(1):130-135

Agroecology and Food Systems Chair, University of Vic-Central University of Catalonia, Vic, Spain.

Background: Evidence from the scientific literature shows a significant variation in greenhouse gas (GHG) emissions from the diet, according to the type of food consumed. We aim to analyze the relationship between the daily dietary GHG emissions according to red meat, fruit and vegetables consumption and their relationship with risk of total mortality, and incident risk of chronic diseases.

Methods: We examined data on the EPIC-Spain prospective study, with a sample of 40 621 participants. Dietary GHG emission values were calculated for 57 food items of the EPIC study using mean emission data from a systematic review of 369 published studies.

Results: Dietary GHG emissions (kgCO2eq/day), per 2000 kcal, were 4.7 times higher in those with high red-meat consumption (>140 g/day) than those with low consumption (<70 g/day). The average dietary GHG emissions were similar in males and females, but it was significantly higher in youngest people and in those individuals with lower educational level, as well as for northern EPIC centers of Spain. We found a significant association with the risk of mortality comparing the third vs. the first tertile of dietary GHG emissions [hazard ratio (HR) 1.095; 95% confidence interval (CI) 1.007-1.19; trend test 0.037]. Risk of coronary heart disease (HR 1.26; 95% CI 1.08-1.48; trend test 0.003) and risk of type 2 diabetes (HR 1.24; 95% CI 1.11-1.38; trend test 0.002) showed significant association as well.

Conclusions: Decreasing red-meat consumption would lead to reduce GHG emissions from diet and would reduce risk of mortality, coronary heart disease and type 2 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurpub/ckaa167DOI Listing
February 2021

Fried-Food Consumption Does Not Increase the Risk of Stroke in the Spanish Cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

J Nutr 2020 12;150(12):3241-3248

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

Background: The nutritional determinants of stroke and, more specifically, the association of frying with the risk of incident stroke have rarely been studied.

Objectives: Our aim was to evaluate prospectively the association between the consumption of fried food and the risk of incident stroke in the European Prospective Investigation into Cancer and Nutrition study using the Spanish cohort.

Methods: Participants included 40,328 healthy adults (62% women) aged 29-69 y at study entry who were enrolled between 1992 and 1996. Participants were followed up until 31 December, 2017, at which time incident stroke (the main outcome) was measured. The main exposure measure was the percentage of energy obtained from fried-food consumption. Sex-specific quintiles were calculated.

Results: During a follow-up period of 23.5 y, 975 cases of stroke occurred (750 ischemic, 185 hemorrhagic, and 40 undetermined). Compared with those in the first (lowest) quintile of fried-food consumption, the multivariate HRs (95% CIs) of incident stroke in the consecutive quintiles were 1.05 (0.86, 1.30), 1.11 (0.90, 1.36), 1.05 (0.84, 1.31), and 0.91 (0.72, 1.15; P-trend = 0.45). There were no differences identified when subtypes of stroke were considered.

Conclusions: In this Spanish cohort, whose participants mainly used olive oil or sunflower oil when frying, the consumption of fried food was not associated with an increased risk of incident stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jn/nxaa272DOI Listing
December 2020

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

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

AOU Federico II, Naples, Italy.

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

Design: Population based cohort study.

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

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

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

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

Conclusions: In this large multinational European cohort, consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj.m3173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491938PMC
September 2020

Replacement of Red and Processed Meat With Other Food Sources of Protein and the Risk of Type 2 Diabetes in European Populations: The EPIC-InterAct Study.

Diabetes Care 2020 11 31;43(11):2660-2667. Epub 2020 Aug 31.

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

Objective: There is sparse evidence for the association of suitable food substitutions for red and processed meat on the risk of type 2 diabetes. We modeled the association between replacing red and processed meat with other protein sources and the risk of type 2 diabetes and estimated its population impact.

Research Design And Methods: The European Prospective Investigation into Cancer (EPIC)-InterAct case cohort included 11,741 individuals with type 2 diabetes and a subcohort of 15,450 participants in eight countries. We modeled the replacement of self-reported red and processed meat with poultry, fish, eggs, legumes, cheese, cereals, yogurt, milk, and nuts. Country-specific hazard ratios (HRs) for incident type 2 diabetes were estimated by Prentice-weighted Cox regression and pooled using random-effects meta-analysis.

Results: There was a lower hazard for type 2 diabetes for the modeled replacement of red and processed meat (50 g/day) with cheese (HR 0.90, 95% CI 0.83-0.97) (30 g/day), yogurt (0.90, 0.86-0.95) (70 g/day), nuts (0.90, 0.84-0.96) (10 g/day), or cereals (0.92, 0.88-0.96) (30 g/day) but not for replacements with poultry, fish, eggs, legumes, or milk. If a causal association is assumed, replacing red and processed meat with cheese, yogurt, or nuts could prevent 8.8%, 8.3%, or 7.5%, respectively, of new cases of type 2 diabetes.

Conclusions: Replacement of red and processed meat with cheese, yogurt, nuts, or cereals was associated with a lower rate of type 2 diabetes. Substituting red and processed meat by other protein sources may contribute to the prevention of incident type 2 diabetes in European populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc20-1038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576430PMC
November 2020

Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries.

BMJ 2020 07 8;370:m2194. Epub 2020 Jul 8.

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

Objective: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes.

Design: Prospective case-cohort study.

Setting: Populations from eight European countries.

Participants: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study.

Main Outcome Measure: Incident type 2 diabetes.

Results: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis.

Conclusions: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj.m2194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341350PMC
July 2020

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

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

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

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

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

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

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

Impact: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-0184DOI Listing
August 2020

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

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

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

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

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32999DOI Listing
October 2020

Serum levels of hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p and subsequent risk of chronic lymphocytic leukemia in the EPIC study.

Int J Cancer 2020 09 2;147(5):1315-1324. Epub 2020 Mar 2.

Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Chronic lymphocytic leukemia (CLL) is an incurable disease accounting for almost one-third of leukemias in the Western world. Aberrant expression of microRNAs (miRNAs) is a well-established characteristic of CLL, and the robust nature of miRNAs makes them eminently suitable liquid biopsy biomarkers. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC), the predictive values of five promising human miRNAs (hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p), identified in a pilot study, were examined in serum of 224 CLL cases (diagnosed 3 months to 18 years after enrollment) and 224 matched controls using Taqman based assays. Conditional logistic regressions were applied to adjust for potential confounders. The median time from blood collection to CLL diagnosis was 10 years (p25-p75: 7-13 years). Overall, the upregulation of hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p was associated with subsequent risk of CLL [OR (95%CI) = 1.42 (1.18-1.72), 1.64 (1.31-2.04) and 1.75 (1.31-2.34) for hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p, respectively] and the strongest associations were observed within 10 years of diagnosis. However, the predictive performance of these miRNAs was modest (area under the curve <0.62). hsa-miR-16-5p and hsa-miR-223-3p levels were unrelated to CLL risk. The findings of this first prospective study suggest that hsa-miR-29a, hsa-miR-150-5p and hsa-miR-155-5p were upregulated in early stages of CLL but were modest predictive biomarkers of CLL risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32894DOI Listing
September 2020

Nutrient-wide association study of 92 foods and nutrients and breast cancer risk.

Breast Cancer Res 2020 01 13;22(1). Epub 2020 Jan 13.

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

Background: Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study.

Methods: Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS).

Results: Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS.

Conclusions: Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13058-019-1244-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958698PMC
January 2020

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

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

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

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

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

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

Conclusions: The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13048-019-0591-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878636PMC
November 2019

Plasma polyphenols associated with lower high-sensitivity C-reactive protein concentrations: a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Br J Nutr 2020 01;123(2):198-208

CIBER de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain.

Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterise the association between plasma concentrations of thirty-five polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis, the OR and 95 % CI of elevated serum hsCRP (>3 mg/l) were calculated within quartiles and per standard deviation higher level of plasma polyphenol concentrations. In a multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per standard deviation) was associated with 29 (95 % CI 50, 1) % lower odds of elevated hsCRP. In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR 0·66, 95 % CI 0·46, 0·96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR 0·58, 95 % CI 0·39, 0·86), 3,4-dihydroxyphenylpropionic acid (OR 0·63, 95 % CI 0·46, 0·87), ferulic acid (OR 0·65, 95 % CI 0·44, 0·96) and caffeic acid (OR 0·69, 95 % CI 0·51, 0·93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR 0·67, 95 % CI 0·48, 0·93). The present study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0007114519002538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015881PMC
January 2020

Prediagnostic Plasma Bile Acid Levels and Colon Cancer Risk: A Prospective Study.

J Natl Cancer Inst 2020 05;112(5):516-524

Hellenic Health Foundation, Athens, Greece.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djz166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225675PMC
May 2020

Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations.

Nutrients 2019 08 20;11(8). Epub 2019 Aug 20.

CIBER Epidemiology and Public Healh (CIBERESP), Madrid 28029, Spain.

Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the , , and genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (, and ). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor β (TGFβ) signaling was associated with CRC risk ( ≤ 0.001), with most statistically significant genes being = 0.008) and = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites ( = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu11081954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722852PMC
August 2019

Reproductive and Lifestyle Factors and Circulating sRANKL and OPG Concentrations in Women: Results from the EPIC Cohort.

Cancer Epidemiol Biomarkers Prev 2019 10 10;28(10):1746-1754. Epub 2019 Jul 10.

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

Background: Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor κB (sRANKL) and OPG concentrations in women are limited. We evaluated reproductive and lifestyle factors as potential sources of variation in circulating sRANKL and OPG concentrations in pre- and postmenopausal women.

Methods: This study includes 2,016 controls [ = 1,552 (76%) postmenopausal, = 757 (38%) using postmenopausal hormone therapy (PMH)] from a breast cancer case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Serum sRANKL was measured using an ELISA and serum OPG using an electrochemiluminescent assay. Generalized linear models were used to evaluate associations between these analytes and reproductive and lifestyle factors.

Results: Older age at blood collection was associated with lower sRANKL concentrations in postmenopausal women ( ≤ 0.03) and higher OPG concentrations in all women ( ≤ 0.01). Longer duration of oral contraceptive use among premenopausal women and postmenopausal PMH users was associated with higher OPG ( ≤ 0.04). In postmenopausal non-PMH users, sRANKL concentrations were lower with longer duration of oral contraceptive use and current (vs. never) smoking ( ≤ 0.01). sRANKL concentrations were higher among women with higher BMI ( ≤ 0.01). The evaluated factors accounted for 12% of the variation in sRANKL concentrations and 21% of the variation in OPG concentrations.

Conclusions: Circulating sRANKL and OPG concentrations are minimally impacted by hormone-related factors in pre- and postmenopausal women.

Impact: This study suggests circulating concentrations of sRANKL and OPG are unlikely to be strongly modified by hormone-related reproductive and lifestyle factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-19-0241DOI Listing
October 2019

Generalizability of a Diabetes-Associated Country-Specific Exploratory Dietary Pattern Is Feasible Across European Populations.

J Nutr 2019 06;149(6):1047-1055

German Cancer Research Center [DKFZ], Heidelberg, Germany.

Background: Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence.

Objective: The aim of this study was to derive country-specific exploratory dietary patterns, investigate their association with type 2 diabetes incidence, and replicate diabetes-associated dietary patterns in other countries.

Methods: Dietary intake data were used, assessed by country-specific questionnaires at baseline of 11,183 incident diabetes cases and 14,694 subcohort members (mean age 52.9 y) from 8 countries, nested within the European Prospective Investigation into Cancer and Nutrition study (mean follow-up time 6.9 y). Exploratory dietary patterns were derived by principal component analysis. HRs for incident type 2 diabetes were calculated by Prentice-weighted Cox proportional hazard regression models. Diabetes-associated dietary patterns were simplified or replicated to be applicable in other countries. A meta-analysis across all countries evaluated the generalizability of the diabetes-association.

Results: Two dietary patterns per country/UK-center, of which overall 3 dietary patterns were diabetes-associated, were identified. A risk-lowering French dietary pattern was not confirmed across other countries: pooled HRFrance per 1 SD: 1.00; 95% CI: 0.90, 1.10. Risk-increasing dietary patterns, derived in Spain and UK-Norfolk, were confirmed, but only the latter statistically significantly: HRSpain: 1.09; 95% CI: 0.97, 1.22 and HRUK-Norfolk: 1.12; 95% CI: 1.04, 1.20. Respectively, this dietary pattern was characterized by relatively high intakes of potatoes, processed meat, vegetable oils, sugar, cake and cookies, and tea.

Conclusions: Only few country/center-specific dietary patterns (3 of 18) were statistically significantly associated with diabetes incidence in this multicountry European study population. One pattern, whose association with diabetes was confirmed across other countries, showed overlaps in the food groups potatoes and processed meat with identified diabetes-associated dietary patterns from other studies. The study demonstrates that replication of associations of exploratory patterns with health outcomes is feasible and a necessary step to overcome population-specificity in associations from such analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jn/nxz031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543295PMC
June 2019

Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status.

Nutrients 2019 Apr 25;11(4). Epub 2019 Apr 25.

Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Spain.

Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only rs11111979 retained borderline statistical significance after adjustment for correlated tests ( = 0.10; significance threshold was < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (, , ) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu11040935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520820PMC
April 2019

Predicting Circulating CA125 Levels among Healthy Premenopausal Women.

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

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

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

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

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

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

Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-18-1120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548604PMC
June 2019

Dairy Product Intake and Risk of Type 2 Diabetes in EPIC-InterAct: A Mendelian Randomization Study.

Diabetes Care 2019 04 6;42(4):568-575. Epub 2019 Feb 6.

Azienda Sanitaria Provinciale (ASP) Ragusa, Ragusa, Italy.

Objective: To estimate the causal association between intake of dairy products and incident type 2 diabetes.

Research Design And Methods: The analysis included 21,820 European individuals (9,686 diabetes cases) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study. Participants were genotyped, and rs4988235 (LCT-12910C>T), a single nucleotide polymorphism (SNP) for lactase persistence (LP) that enables digestion of dairy sugar, i.e., lactose, was imputed. Baseline dietary intakes were assessed with diet questionnaires. We investigated the associations between imputed SNP dosage for rs4988235 and intake of dairy products and other foods through linear regression. Mendelian randomization (MR) estimates for the milk-diabetes relationship were obtained through a two-stage least squares regression.

Results: Each additional LP allele was associated with a higher intake of milk (β 17.1 g/day, 95% CI 10.6-23.6) and milk beverages (β 2.8 g/day, 95% CI 1.0-4.5) but not with intake of other dairy products. Other dietary intakes associated with rs4988235 included fruits (β -7.0 g/day, 95% CI -12.4 to -1.7 per additional LP allele), nonalcoholic beverages (β -18.0 g/day, 95% CI -34.4 to -1.6), and wine (β -4.8 g/day, 95% CI -9.1 to -0.6). In instrumental variable analysis, LP-associated milk intake was not associated with diabetes (hazard ratio 0.99, 95% CI 0.93-1.05).

Conclusions: rs4988235 was associated with milk intake but not with intake of other dairy products. This MR study does not suggest that milk intake is associated with diabetes, which is consistent with previous observational and genetic associations. LP may be associated with intake of other foods as well, but owing to the modest associations, we consider it unlikely that this caused the observed null result.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc18-2034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340535PMC
April 2019

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

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

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

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

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32091DOI Listing
July 2019

Gallstones and incident colorectal cancer in a large pan-European cohort study.

Int J Cancer 2019 09 11;145(6):1510-1516. Epub 2019 Jan 11.

Cancer Registry and Histopathology Department, "Civic - M.P.Arezzo" Hospital, Ragusa, Italy.

Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self-reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow-up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR = 1.14, 95%CI 0.99-1.31, p = 0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR = 0.81, 95%CI 0.63-1.04, p = 0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32090DOI Listing
September 2019

Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Eur J Nutr 2019 Dec 10;58(8):3303-3312. Epub 2018 Dec 10.

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

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 (HR 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 (HR 0.98, 95% CI 0.95-1.02) and papillary tumor (HR 0.99, 95% CI 0.95-1.03), whereas an inverse association was found with follicular tumor risk (HR 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00394-018-1874-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850907PMC
December 2019

Helicobacter pylori seroprevalence in Spain: influence of adult and childhood sociodemographic factors.

Eur J Cancer Prev 2019 07;28(4):294-303

Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública, CIBERESP).

Helicobacter pylori (H. pylori) chronic infection causes severe digestive diseases, including gastric cancer, and certain strains entail a higher risk. Risk factors for this infection are still not fully understood. The aim of this study was to describe the association of adult and childhood sociodemographic factors with the seroprevalence of H. pylori, and with CagA and VacA antigen-specific seropositivity among H. pylori-seropositive individuals in the Spanish adult population. Serum antibody reactivity to H. pylori proteins was evaluated using multiplex serology in 2555 population-based controls enrolled in the MCC-Spain study, a multicase-control study recruiting participants from 2008 to 2013 in different areas of Spain. H. pylori seroprevalence was defined as seropositivity against at least four bacterial proteins. Information on sociodemographics, lifestyles, and environmental exposures was collected through personal interviews. Prevalence ratios and 95% confidence intervals were estimated using Poisson regression models to assess the association of lifetime sociodemographic factors with H. pylori seroprevalence and with seropositivity for CagA and VacA. H. pylori seroprevalence was 87.2%. Seropositivity was statistically significantly higher in men, increased with age, BMI, and number of siblings, and decreased with education and socioeconomic family level at birth. Among H. pylori-seropositive individuals, seropositivity was 53.3% for CagA, 61.4% for VacA, and 38.8% for both CagA and VacA. Ever smokers had lower seroprevalence for CagA and VacA than never smokers. H. pylori seroprevalence among this Spanish adult population was high and one third of the population was seropositive for two well-known markers of gastric cancer risk: CagA and VacA. Sex, age, education, and BMI were associated with H. pylori seroprevalence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CEJ.0000000000000483DOI Listing
July 2019

CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer: a prospective evaluation.

Int J Cancer 2019 04 4;144(8):1877-1887. Epub 2018 Dec 4.

Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.

Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. Our study provides a first prospective evaluation of an ApoA2 isoform ("ApoA2-ATQ/AT"), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤ 18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤ 18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.31900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760974PMC
April 2019
-->