Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Correction to: Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer
Bien, Stephanie A. ; Su, Yu Ru ; Conti, David V. ; Harrison, Tabitha A. ; Qu, Conghui ; Guo, Xingyi ; Lu, Yingchang ; Albanes, Demetrius ; Auer, Paul L. ; Banbury, Barbara L. ; Berndt, Sonja I. ; Bézieau, Stéphane ; Brenner, Hermann ; Buchanan, Daniel D. ; Caan, Bette J. ; Campbell, Peter T. ; Carlson, Christopher S. ; Chan, Andrew T. ; Chang-Claude, Jenny ; Chen, Sai ; Connolly, Charles M. ; Easton, Douglas F. ; Feskens, Edith J.M. ; Gallinger, Steven ; Giles, Graham G. ; Gunter, Marc J. ; Hampe, Jochen ; Huyghe, Jeroen R. ; Hoffmeister, Michael ; Hudson, Thomas J. ; Jacobs, Eric J. ; Jenkins, Mark A. ; Kampman, Ellen ; Kang, Hyun Min ; Kühn, Tilman ; Küry, Sébastien ; Lejbkowicz, Flavio ; Marchand, Loic Le; Milne, Roger L. ; Li, Li ; Li, Christopher I. ; Lindblom, Annika ; Lindor, Noralane M. ; Martín, Vicente ; McNeil, Caroline E. ; Melas, Marilena ; Moreno, Victor ; Newcomb, Polly A. ; Offit, Kenneth ; Pharaoh, Paul D.P. ; Potter, John D. ; Qu, Chenxu ; Riboli, Elio ; Rennert, Gad ; Sala, Núria ; Schafmayer, Clemens ; Scacheri, Peter C. ; Schmit, Stephanie L. ; Severi, Gianluca ; Slattery, Martha L. ; Smith, Joshua D. ; Trichopoulou, Antonia ; Tumino, Rosario ; Ulrich, Cornelia M. ; Duijnhoven, Fränzel J.B. van; Guelpen, Bethany Van; Weinstein, Stephanie J. ; White, Emily ; Wolk, Alicja ; Woods, Michael O. ; Wu, Anna H. ; Abeçasis, Goncalo R. ; Casey, Graham ; Nickerson, Deborah A. ; Gruber, Stephen B. ; Hsu, Li ; Zheng, Wei ; Peters, Ulrike - \ 2019
Human Genetics 138 (2019)7. - ISSN 0340-6717 - p. 789 - 791.

Every author has erroneously been assigned to the affiliation “62”. The affiliation 62 belongs to the author Graham Casey.

Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer
Bien, Stephanie A. ; Su, Yu-Ru ; Conti, David V. ; Harrison, Tabitha A. ; Qu, Conghui ; Guo, Xingyi ; Lu, Yingchang ; Albanes, Demetrius ; Auer, Paul L. ; Banbury, Barbara L. ; Berndt, Sonja I. ; Bézieau, Stéphane ; Brenner, Hermann ; Buchanan, Daniel D. ; Caan, Bette J. ; Campbell, Peter T. ; Carlson, Christopher S. ; Chan, Andrew T. ; Chang-Claude, Jenny ; Chen, Sai ; Connolly, Charles M. ; Easton, Douglas F. ; Feskens, Edith J.M. ; Gallinger, Steven ; Giles, Graham G. ; Gunter, Marc J. ; Hampe, Jochen ; Huyghe, Jeroen R. ; Hoffmeister, Michael ; Hudson, Thomas J. ; Jacobs, Eric J. ; Jenkins, Mark A. ; Kampman, Ellen ; Kang, Hyun Min ; Kühn, Tilman ; Küry, Sébastien ; Lejbkowicz, Flavio ; Marchand, Loic Le; Milne, Roger L. ; Li, Christopher I. ; Lindblom, Annika ; Lindor, Noralane M. ; Martín, Vicente ; McNeil, Caroline E. ; Melas, Marilena ; Moreno, Victor ; Newcomb, Polly A. ; Offit, Kenneth ; Pharaoh, Paul D.P. ; Potter, John D. ; Qu, Chenxu ; Riboli, Elio ; Rennert, Gad ; Sala, Núria ; Schafmayer, Clemens ; Scacheri, Peter C. ; Schmit, Stephanie L. ; Severi, Gianluca ; Slattery, Martha L. ; Smith, Joshua D. ; Trichopoulou, Antonia ; Tumino, Rosario ; Ulrich, Cornelia M. ; Duijnhoven, Fränzel J.B. van; Guelpen, Bethany Van; Weinstein, Stephanie J. ; White, Emily ; Wolk, Alicja ; Woods, Michael O. ; Wu, Anna H. ; Abecasis, Goncalo R. ; Casey, Graham ; Nickerson, Deborah A. ; Gruber, Stephen B. ; Hsu, Li ; Zheng, Wei ; Peters, Ulrike - \ 2019
Human Genetics 138 (2019)4. - ISSN 0340-6717 - p. 307 - 326.
Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n = 169) and whole blood (n = 922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR ≤ 0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P = 2.2 × 10− 4, replication P = 0.01), and PYGL (discovery P = 2.3 × 10− 4, replication P = 6.7 × 10− 4). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P < 0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci.
Prediagnostic serum Vitamin D levels and the risk of Crohn's disease and ulcerative colitis in european populations : A nested case-control study
Opstelten, Jorrit L. ; Chan, Simon S.M. ; Hart, Andrew R. ; Schaik, Fiona D.M. Van; Siersema, Peter D. ; Lentjes, Eef G.W.M. ; Khaw, Kay Tee ; Luben, Robert ; Key, Timothy J. ; Boeing, Heiner ; Bergmann, Manuela M. ; Overvad, Kim ; Palli, Domenico ; Masala, Giovanna ; Racine, Antoine ; Carbonnel, Franck ; Boutron-Ruault, Marie Christine ; Tjønneland, Anne ; Olsen, Anja ; Andersen, Vibeke ; Kaaks, Rudolf ; Kuhn, Tilman ; Tumino, Rosario ; Trichopoulou, Antonia ; Peeters, Petra H.M. ; Verschuren, W.M.M. ; Witteman, Ben J.M. ; Oldenburg, Bas - \ 2018
Inflammatory Bowel Diseases 24 (2018)3. - ISSN 1078-0998 - p. 633 - 640.
Crohn's disease - etiology - inflammatory bowel disease - ulcerative colitis - Vitamin D

Background A low vitamin D status has been put forward as a potential risk factor for the development of inflammatory bowel disease (IBD). This study investigated the association between prediagnostic circulating vitamin D concentrations and dietary intakes of vitamin D, and the risk of Crohn's disease (CD) and ulcerative colitis (UC). Methods Among 359,728 participants of the European Prospective Investigation into Cancer and Nutrition cohort, individuals who developed CD or UC after enrollment were identified. Each case was matched with2 controls by center, gender, age, date of recruitment, and follow-up time. At cohort entry, blood samples were collected and dietary vitamin D intakes were obtained from validated food frequency questionnaires. Serum 25-hydroxyvitamin D levels were measured using liquid chromatography-tandem mass spectrometry. Conditional logistic regression was performed to determine the odds of CD and UC. Results Seventy-two participants developed CD and 169 participants developed UC after a median follow-up of 4.7 and 4.1 years, respectively. Compared with the lowest quartile, no associations with the 3 higher quartiles of vitamin D concentrations were observed for CD (p trend = 0.34) or UC (p trend = 0.66). Similarly, no associations were detected when serum vitamin D levels were analyzed as a continuous variable. Dietary vitamin D intakes were not associated with CD (p trend = 0.39) or UC (p trend = 0.83). Conclusions Vitamin D status was not associated with the development of CD or UC. This does not suggest a major role for vitamin D deficiency in the etiology of IBD, although larger studies are needed to confirm these findings.

Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations
Duijnhoven, Fränzel J.B. van; Jenab, Mazda ; Hveem, Kristian ; Siersema, Peter D. ; Fedirko, Veronika ; Duell, Eric J. ; Kampman, Ellen ; Halfweeg, Anouk ; Kranen, Henk J. van; Ouweland, Jody M.W. van den; Weiderpass, Elisabete ; Murphy, Neil ; Langhammer, Arnulf ; Ness-Jensen, Eivind ; Olsen, Anja ; Tjønneland, Anne ; Overvad, Kim ; Cadeau, Claire ; Kvaskoff, Marina ; Boutron-Ruault, Marie Christine ; Katzke, Verena A. ; Kühn, Tilman ; Boeing, Heiner ; Trichopoulou, Antonia ; Kotanidou, Anastasia ; Kritikou, Maria ; Palli, Domenico ; Agnoli, Claudia ; Tumino, Rosario ; Panico, Salvatore ; Matullo, Giuseppe ; Peeters, Petra ; Brustad, Magritt ; Olsen, Karina Standahl ; Lasheras, Cristina ; Obón-Santacana, Mireia ; Sánchez, María José ; Dorronsoro, Miren ; Chirlaque, Maria Dolores ; Barricarte, Aurelio ; Manjer, Jonas ; Almquist, Martin ; Renström, Frida ; Ye, Weimin ; Wareham, Nick ; Khaw, Kay Tee ; Bradbury, Kathryn E. ; Freisling, Heinz ; Aune, Dagfinn ; Norat, Teresa ; Riboli, Elio ; Bueno-de-Mesquita, H.B. - \ 2018
International Journal of Cancer 142 (2018)6. - ISSN 0020-7136 - p. 1189 - 1201.
Cancer epidemiology - Nested case-control study - Pancreatic cancer - Vitamin D
Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n=626; HUNT2 n=112; median follow-up=6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend=0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend=0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.
Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study
Zheng, Ju-Sheng ; Sharp, Stephen J. ; Imamura, Fumiaki ; Koulman, Albert ; Schulze, Matthias B. ; Ye, Zheng ; Griffin, Jules ; Guevara, Marcela ; Huerta, José María ; Kröger, Janine ; Sluijs, Ivonne ; Agudo, Antonio ; Barricarte, Aurelio ; Boeing, Heiner ; Colorado-Yohar, Sandra ; Dow, Courtney ; Dorronsoro, Miren ; Dinesen, Pia T. ; Fagherazzi, Guy ; Franks, Paul W. ; Feskens, Edith J.M. ; Kühn, Tilman ; Katzke, Verena Andrea ; Key, Timothy J. ; Khaw, Kay-Tee ; Magistris, Maria Santucci De; Mancini, Francesca Romana ; Molina-Portillo, Elena ; Nilsson, Peter M. ; Olsen, Anja ; Overvad, Kim ; Palli, Domenico ; Quirós, Jose Ramón ; Rolandsson, Olov ; Ricceri, Fulvio ; Spijkerman, Annemieke M.W. ; Slimani, Nadia ; Tagliabue, Giovanna ; Tjonneland, Anne ; Tumino, Rosario ; Schouw, Yvonne T. Van Der; Langenberg, Claudia ; Riboli, Elio ; Forouhi, Nita G. ; Wareham, Nicholas J. - \ 2017
BMC Medicine 15 (2017)1. - ISSN 1741-7015
Background
Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways.
Methods
We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested.
Results
Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption.
Conclusions
Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.
Genome-wide association analysis for lodging tolerance and plant height in a diverse European hexaploid oat collection
Tumino, Giorgio ; Voorrips, Roeland E. ; Morcia, Caterina ; Ghizzoni, Roberta ; Germeier, Christoph U. ; Caldas Paulo, Joao ; Terzi, Valeria ; Smulders, Marinus J.M. - \ 2017
Euphytica 213 (2017)8. - ISSN 0014-2336
Avena sativa - Genome-wide association study - Lodging - Plant height - SNP array intensity ratio

Sensitivity to lodging of oat varieties has been reduced in the last decades through the introduction of dwarfing genes. However, lodging may still cause significant yield loss, underscoring the need for new oat varieties with higher levels of lodging tolerance. In the present study, we analysed lodging and plant height in a collection of European oat accessions including landraces, old and modern varieties, in order to perform a genome-wide association study (GWAS) for identifying markers associated to lodging tolerance. This collection has been recently genotyped by the Infinium 6K SNP array for oat and SNP data were analysed as continuous intensity ratios, rather than as discrete genotypes (Tumino et al. 2016, Theor Appl Genet 129, pp. 1711–1724). Phenotypes for lodging severity, plant height and growth habit were collected under natural conditions in eight European countries. Plant height correlated to lodging severity as previously observed in many studies, explaining about 30% of lodging variation. GWAS analyses detected six significant associations for lodging and two for plant height. These results indicate that GWAS can successfully be used for identifying markers associated to lodging in oat, even though lodging is a quantitative trait influenced by several plant characteristics.

Pre-diagnostic meat and fibre intakes in relation to colorectal cancer survival in the European Prospective Investigation into Cancer and Nutrition
Ward, Heather A. ; Norat, Teresa ; Overvad, Kim ; Dahm, Christina C. ; Bueno-de-Mesquita, H.B. ; Jenab, Mazda ; Fedirko, Veronika ; Duijnhoven, Fränzel J.B. Van; Skeie, Guri ; Romaguera-Bosch, Dora ; Tjonneland, Anne ; Olsen, Anja ; Carbonnel, Franck ; Affret, Aurélie ; Boutron-Ruault, Marie Christine ; Katzke, Verena ; Kühn, Tilman ; Aleksandrova, Krassimira ; Boeing, Heiner ; Trichopoulou, Antonia ; Lagiou, Pagona ; Bamia, Christina ; Palli, Domenico ; Sieri, Sabina ; Tumino, Rosario ; Naccarati, Alessio ; Mattiello, Amalia ; Peeters, Petra H. ; Weiderpass, Elisabete ; Åsli, Lene Angell ; Jakszyn, Paula ; Ramón Quirós, J. ; Sánchez, María José ; Dorronsoro, Miren ; Huerta, José María ; Barricarte, Aurelio ; Jirström, Karin ; Ericson, Ulrika ; Johansson, Ingegerd ; Gylling, Björn ; Bradbury, Kathryn E. ; Khaw, Kay Tee ; Wareham, Nicholas J. ; Stepien, Magdalena ; Freisling, Heinz ; Murphy, Neil ; Cross, Amanda J. ; Riboli, Elio - \ 2016
The British journal of nutrition 116 (2016)2. - ISSN 0007-1145 - p. 316 - 325.
Cancer survival - Cohorts - Colorectal cancers - Diets - European Prospective Investigation into Cancer and Nutrition
Improvements in colorectal cancer (CRC) detection and treatment have led to greater numbers of CRC survivors, for whom there is limited evidence on which to provide dietary guidelines to improve survival outcomes. Higher intake of red and processed meat and lower intake of fibre are associated with greater risk of developing CRC, but there is limited evidence regarding associations with survival after CRC diagnosis. Among 3789 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, pre-diagnostic consumption of red meat, processed meat, poultry and dietary fibre was examined in relation to CRC-specific mortality (n 1008) and all-cause mortality (n 1262) using multivariable Cox regression models, adjusted for CRC risk factors. Pre-diagnostic red meat, processed meat or fibre intakes (defined as quartiles and continuous grams per day) were not associated with CRC-specific or all-cause mortality among CRC survivors; however, a marginal trend across quartiles of processed meat in relation to CRC mortality was detected (P 0·053). Pre-diagnostic poultry intake was inversely associated with all-cause mortality among women (hazard ratio (HR)/20 g/d 0·92; 95 % CI 0·84, 1·00), but not among men (HR 1·00; 95 % CI 0·91, 1·09) (P for heterogeneity=0·10). Pre-diagnostic intake of red meat or fibre is not associated with CRC survival in the EPIC cohort. There is suggestive evidence of an association between poultry intake and all-cause mortality among female CRC survivors and between processed meat intake and CRC-specific mortality; however, further research using post-diagnostic dietary data is required to confirm this relationship.
Anthropometry and the risk of lung cancer in EPIC
Dewi, Nikmah Utami ; Boshuizen, Hendriek C. ; Johansson, Mattias ; Vineis, Paolo ; Kampman, Ellen ; Steffen, Annika ; Tjønneland, Anne ; Halkjær, Jytte ; Overvad, Kim ; Severi, Gianluca ; Fagherazzi, Guy ; Boutron-Ruault, Marie Christine ; Kaaks, Rudolf ; Li, Kuanrong ; Boeing, Heiner ; Trichopoulou, Antonia ; Bamia, Christina ; Klinaki, Eleni ; Tumino, Rosario ; Palli, Domenico ; Mattiello, Amalia ; Tagliabue, Giovanna ; Peeters, Petra H. ; Vermeulen, Roel ; Weiderpass, Elisabete ; Gram, Inger Torhild ; Huerta, José María ; Agudo, Antonio ; Sánchez, María José ; Ardanaz, Eva ; Dorronsoro, Miren ; Quirós, José Ramón ; Sonestedt, Emily ; Johansson, Mikael ; Grankvist, Kjell ; Key, Tim ; Khaw, Kay Tee ; Wareham, Nick ; Cross, Amanda J. ; Norat, Teresa ; Riboli, Elio ; Fanidi, Anouar ; Muller, David ; Bueno-De-Mesquita, H.B. - \ 2016
American Journal of Epidemiology 184 (2016)2. - ISSN 0002-9262 - p. 129 - 139.
body mass index - lung cancer - obesity - smoking - waist circumference - waist to hip ratio - waist-to-height ratio

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

Population structure and genome-wide association analysis for frost tolerance in oat using continuous SNP array signal intensity ratios
Tumino, Giorgio ; Voorrips, Roeland E. ; Rizza, Fulvia ; Badeck, Franz W. ; Morcia, Caterina ; Ghizzoni, Roberta ; Germeier, Christoph U. ; Paulo, Maria João ; Terzi, Valeria ; Smulders, Marinus J.M. - \ 2016
Theoretical and Applied Genetics 129 (2016)9. - ISSN 0040-5752 - p. 1711 - 1724.

Key message: Infinium SNP data analysed as continuous intensity ratios enabled associating genotypic and phenotypic data from heterogeneous oat samples, showing that association mapping for frost tolerance is a feasible option.Abstract: Oat is sensitive to freezing temperatures, which restricts the cultivation of fall-sown or winter oats to regions with milder winters. Fall-sown oats have a longer growth cycle, mature earlier, and have a higher productivity than spring-sown oats, therefore improving frost tolerance is an important goal in oat breeding. Our aim was to test the effectiveness of a Genome-Wide Association Study (GWAS) for mapping QTLs related to frost tolerance, using an approach that tolerates continuously distributed signals from SNPs in bulked samples from heterogeneous accessions. A collection of 138 European oat accessions, including landraces, old and modern varieties from 27 countries was genotyped using the Infinium 6K SNP array. The SNP data were analyzed as continuous intensity ratios, rather than converting them into discrete values by genotype calling. PCA and Ward’s clustering of genetic similarities revealed the presence of two main groups of accessions, which roughly corresponded to Continental Europe and Mediterranean/Atlantic Europe, although a total of eight subgroups can be distinguished. The accessions were phenotyped for frost tolerance under controlled conditions by measuring fluorescence quantum yield of photosystem II after a freezing stress. GWAS were performed by a linear mixed model approach, comparing different corrections for population structure. All models detected three robust QTLs, two of which co-mapped with QTLs identified earlier in bi-parental mapping populations. The approach used in the present work shows that SNP array data of heterogeneous hexaploid oat samples can be successfully used to determine genetic similarities and to map associations to quantitative phenotypic traits.

Colorectal cancer risk and dyslipidemia: a case-cohort study nested in an Italian multicentre cohort
Agnoli, C. ; Grioni, S. ; Sieri, S. ; Sacerdote, C. ; Vineis, P. ; Tumino, R. ; Giurdanella, M.C. ; Pala, V. ; Mattiello, A. ; Chiodini, P. ; Iacoviello, L. ; Curtis, A. de; Cattaneo, L. ; Duijnhoven, F.J.B. van - \ 2014
Cancer Epidemiology 38 (2014)2. - ISSN 1877-7821 - p. 144 - 151.
metabolic syndrome - serum-cholesterol - colon-cancer - lipoprotein levels - blood-cholesterol - glucose - triglyceride - association - nutrition - lipids
Background: Dyslipidemia is an established risk factor for many diseases, but its effect on colorectal cancer risk is less clear. We investigated the association of colorectal cancer risk with plasma triglycerides, total, HDL, and LDL cholesterol in four Italian EPIC centers. Methods: We conducted a case-cohort study on participants recruited to four Italian EPIC centers (Turin, Varese, Naples, and Ragusa; 34,148 subjects). A random subcohort of 850 subjects was obtained and 286 colorectal cancer cases were diagnosed. Triglycerides, total and HDL cholesterol were determined in plasma samples obtained at baseline and stored at -196 degrees C; LDL cholesterol was calculated. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Cox regression models using the Prentice method. Results: The highest tertiles of total (HR 1.66, 95% CI 1.12-2.45) and LDL cholesterol (HR 1.87, 95% CI 1.27-2.76) were associated with increased colorectal cancer risk compared to lowest tertiles. Risks were greater for men than women, and for postmenopausal than premenopausal women. Highest tertiles of total and LDL cholesterol were also significantly associated with increased risks of colon cancer, distal colon cancer, and rectal cancer, but not proximal colon cancer. Conclusions: Our findings suggest that high levels of total and LDL cholesterol increase colorectal cancer risk, particularly in men and postmenopausal women. However additional studies are needed to clarify the role of plasma lipids in these cancers, particularly in view of the conflicting findings of previous studies. (C) 2014 Elsevier Ltd. All rights reserved.
Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort
Dossus, L. ; Boutron-Ruault, M.C. ; Kaaks, R. ; Gram, I.T. ; Vilier, A. ; Fervers, B. ; Manjer, J. ; Tjonneland, A. ; Olsen, A. ; Overvad, K. ; Chang-Claude, J. ; Boeing, H. ; Steffen, A. ; Trichopoulou, A. ; Lagiou, P. ; Sarantopoulou, M. ; Palli, D. ; Berrino, F. ; Tumino, R. ; Vineis, P. ; Mattiello, A. ; Bueno-de-Mesquita, H.B. ; Duijnhoven, F.J.B. van - \ 2014
International Journal of Cancer 134 (2014)8. - ISSN 0020-7136 - p. 1871 - 1888.
environmental tobacco-smoke - postmenopausal women - california teachers - 1st childbirth - never smokers - exposure - metaanalysis - association - carcinogens - reanalysis
Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05–1.28], 1.14 [1.04–1.25] and 1.10 [1.01–1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29–2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34–0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious.
Lifestyle factors and mortality risk in individuals with diabetes mellitus: are the associations different from those in individuals without diabetes?
Sluik, D. ; Boeing, H. ; Li, K. ; Fons Johnsen, N. ; Tjonneland, A. ; Arriola, L. ; Barricarte, A. ; Masala, G. ; Grioni, S. ; Tumino, R. ; Ricceri, F. ; Matiello, A. ; Spijkerman, A.M.W. ; A, D.L. van der; Sluijs, I. van der - \ 2014
Diabetologia 57 (2014)1. - ISSN 0012-186X - p. 63 - 72.
food frequency questionnaire - american-heart-association - cardiovascular-disease - multiple imputation - relative validity - physical-activity - clinical-research - missing data - dietary-fat - cancer
Aims/hypothesis Thus far, it is unclear whether lifestyle recommendations for people with diabetes should be different from those for the general public. We investigated whether the associations between lifestyle factors and mortality risk differ between individuals with and without diabetes. Methods Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort was formed of 6,384 persons with diabetes and 258,911 EPIC participants without known diabetes. Joint Cox proportional hazard regression models of people with and without diabetes were built for the following lifestyle factors in relation to overall mortality risk: BMI, waist/height ratio, 26 food groups, alcohol consumption, leisure-time physical activity, smoking. Likelihood ratio tests for heterogeneity assessed statistical differences in regression coefficients. Results Multivariable adjusted mortality risk among individuals with diabetes compared with those without was increased, with an HR of 1.62 (95% CI 1.51, 1.75). Intake of fruit, legumes, nuts, seeds, pasta, poultry and vegetable oil was related to a lower mortality risk, and intake of butter and margarine was related to an increased mortality risk. These associations were significantly different in magnitude from those in diabetes-free individuals, but directions were similar. No differences between people with and without diabetes were detected for the other lifestyle factors. Conclusions/interpretation Diabetes status did not substantially influence the associations between lifestyle and mortality risk. People with diabetes may benefit more from a healthy diet, but the directions of association were similar. Thus, our study suggests that lifestyle advice with respect to mortality for patients with diabetes should not differ from recommendations for the general population.
Erratum to: Bias in protein and potassium intake collected with 24-h recalls (EPIC-Soft) is rather comparable across European populations
Crispim, Sandra P. ; Geelen, Anouk ; Vries, Jeanne H.M. De; Freisling, Heinz ; Souverein, Olga W. ; Hulshof, Paul J.M. ; Ocke, Marga C. ; Boshuizen, Hendriek ; Andersen, Lene F. ; Ruprich, Jiri ; Keyzer, Willem De; Huybrechts, Inge ; Lafay, Lionel ; Magistris, Maria S. De; Ricceri, Fulvio ; Tumino, Rosario ; Krogh, Vittorio ; Bueno-De-Mesquita, H.B. ; Beulens, Joline W.J. ; Boutron-Ruault, Marie Christine ; Naska, Androniki ; Crowe, Francesca L. ; Boeing, Heiner ; McTaggart, Alison ; Kaaks, Rudolf ; Veer, Pieter van 't; Slimani, Nadia - \ 2013
European Journal of Nutrition 52 (2013)2. - ISSN 1436-6207 - p. 857 - 858.
Fruit and Vegetable Consumption and Mortality: European Prospective Investigation Into Cancer and Nutrition
Leenders, M. ; Sluijs, I. van der; Ros, M.M. ; Boshuizen, H.C. ; Siersema, P.D. ; Ferrari, P. ; Weikert, C. ; Tjonneland, A. ; Olsen, A. ; Boutron-Ruault, M.C. ; Clavel-Chapelon, F. ; Nailler, L. ; Teucher, B. ; Li, K.R. ; Boeing, H. ; Bergmann, M.M. ; Trichopoulou, A. ; Lagiou, P. ; Trichopoulos, D. ; Palli, D. ; Pala, V. ; Panico, S. ; Tumino, R. ; Sacerdote, C. ; Peeters, P.H.M. ; Gils, C.H. van; Lund, E. ; Engeset, D. ; Redondo, M.L. ; Agudo, A. ; Sanchez, M.J. ; Navarro, C. ; Ardanaz, E. ; Sonestedt, E. ; Ericson, U. ; Nilsson, L.M. ; Khaw, K.T. ; Warcham, N.J. ; Key, T.J. ; Crowe, F.L. ; Romieu, I. ; Gunter, M.J. ; Gallo, V. ; Overvad, K. ; Riboli, E. ; Bueno-de-Mesquita, H.B. - \ 2013
American Journal of Epidemiology 178 (2013)4. - ISSN 0002-9262 - p. 590 - 602.
cardiovascular-disease - oxidative stress - heart-disease - dietary assessment - risk - population - impact - men - calibration - health
In this study, the relation between fruit and vegetable consumption and mortality was investigated within the European Prospective Investigation Into Cancer and Nutrition. Survival analyses were performed, including 451,151 participants from 10 European countries, recruited between 1992 and 2000 and followed until 2010. Hazard ratios, rate advancement periods, and preventable proportions to respectively compare risk of death between quartiles of consumption, to estimate the period by which the risk of death was postponed among high consumers, and to estimate proportions of deaths that could be prevented if all participants would shift their consumption 1 quartile upward. Consumption of fruits and vegetables was inversely associated with all-cause mortality (for the highest quartile, hazard ratio = 0.90, 95% confidence interval (CI): 0.86, 0.94), with a rate advancement period of 1.12 years (95% CI: 0.70, 1.54), and with a preventable proportion of 2.95%. This association was driven mainly by cardiovascular disease mortality (for the highest quartile, hazard ratio = 0.85, 95% CI: 0.77, 0.93). Stronger inverse associations were observed for participants with high alcohol consumption or high body mass index and suggested in smokers. Inverse associations were stronger for raw than for cooked vegetable consumption. These results support the evidence that fruit and vegetable consumption is associated with a lower risk of death.
Nort-South gradients in plasma concentrations of B-vitamins and other components of one-carbon metabolism in Western Europe: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study
Eussen, S.J.P.M. ; Nilsen, R.M. ; Midttun, O. ; Hustad, S. ; IJssenagger, N. ; Meyer, K. ; Fredriksen, A. ; Ulvik, A. ; Ueland, P.M. ; Brennan, P. ; Johansson, M. ; Bueno-de-Mesquita, B. ; Vineis, P. ; Chuang, S.C. ; Boutron-Ruault, M.C. ; Dossus, L. ; Perquier, F. ; Overvad, K. ; Teucher, B. ; Grote, V.A. ; Trichopoulou, A. ; Adarakis, G. ; Plada, M. ; Sieri, S. ; Tumino, R. ; Santucci de Magistris, M. ; Ros, M.M. ; Peeters, P.H.M. ; Redondo, M.L. ; Zamora-Ros, R. ; Chirlaque, M.D. ; Ardanaz, E. ; Sonestedt, E. ; Ericson, U. ; Schneede, J. ; Guelpen, B. ; Wark, P.A. ; Gallo, V. ; Norat, T. ; Riboli, E. ; Vollset, S.E. - \ 2013
The British journal of nutrition 110 (2013)2. - ISSN 0007-1145 - p. 363 - 374.
tandem mass-spectrometry - 24-hour dietary recalls - colorectal-cancer - homocysteine metabolism - microbiological assay - alcohol-consumption - nutrient intake - dairy-products - folate intake - 10 countries
Different lifestyle patterns across Europe may influence plasma concentrations of B-vitamins and one-carbon metabolites and their relation to chronic disease. Comparison of published data on one-carbon metabolites in Western European regions is difficult due to differences in sampling procedures and analytical methods between studies. The present study aimed, to compare plasma concentrations of one-carbon metabolites in Western European regions with one laboratory performing all biochemical analyses. We performed the present study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort among 5446 presumptively healthy individuals. Quantile regression was used to compare sex-specific median concentrations between Northern (Denmark and Sweden), Central (France, Germany, The Netherlands and United Kingdom) and Southern (Greece, Spain and Italy) European regions. The lowest folate concentrations were observed in Northern Europe (men, 10·4 nmol/l; women, 10·7 nmol/l) and highest concentrations in Central Europe. Cobalamin concentrations were slightly higher in Northern Europe (men, 330 pmol/l; women, 352 pmol/l) compared with Central and Southern Europe, but did not show a clear north–south gradient. Vitamin B2 concentrations were highest in Northern Europe (men, 22·2 nmol/l; women, 26·0 nmol/l) and decreased towards Southern Europe (P trend <0·001). Vitamin B6 concentrations were highest in Central Europe in men (77·3 nmol/l) and highest in the North among women (70·4 nmol/l), with decreasing concentrations towards Southern Europe in women (P trend <0·001). In men, concentrations of serine, glycine and sarcosine increased from the north to south. In women, sarcosine increased from Northern to Southern Europe. These findings may provide relevant information for the study of regional differences of chronic disease incidence in association with lifestyle.
Dietary Fibre Intake and Risks of Cancers of the Colon and Rectum in the European Prospective Investigation into Cancer and Nutrition (EPIC)
Murphy, N. ; Norat, T. ; Ferrari, P. ; Jenab, M. ; Bueno-de-Mesquita, B. ; Skeie, G. ; Dahm, C.C. ; Overvad, K. ; Olsen, A. ; Tjonneland, A. ; Clavel-Chapelon, F. ; Boutron-Ruault, M.C. ; Racine, A. ; Kaaks, R. ; Teucher, B. ; Boeing, H. ; Bergmann, M.M. ; Trichopoulou, A. ; Trichopoulos, D. ; Lagiou, P. ; Palli, D. ; Pala, V. ; Panico, S. ; Tumino, R. ; Vineis, P. ; Siersema, P. ; Duijnhoven, F.J.B. van; Peeters, P.H.M. ; Hjartaker, A. ; Engeset, D. ; Gonzalez, C.A. ; Sanchez, M.J. ; Dorronsoro, M. ; Navarro, C. ; Ardanaz, E. ; Quiros, J.R. ; Sonestedt, E. ; Ericson, U. ; Nilsson, L. ; Palmqvist, R. ; Khaw, K.T. ; Wareham, N. ; Key, T.J. ; Crowe, F.L. ; Fedirko, V. ; Wark, P.A. ; Chuang, S.C. ; Riboli, E. - \ 2012
PLoS ONE 7 (2012)6. - ISSN 1932-6203
colorectal-cancer - nonstarch polysaccharides - epidemiologic evidence - measurement error - glycemic index - cohort - project - carbohydrate - calibration - protection
Background: Earlier analyses within the EPIC study showed that dietary fibre intake was inversely associated with colorectal cancer risk, but results from some large cohort studies do not support this finding. We explored whether the association remained after longer follow-up with a near threefold increase in colorectal cancer cases, and if the association varied by gender and tumour location. Methodology/Principal Findings: After a mean follow-up of 11.0 years, 4,517 incident cases of colorectal cancer were documented. Total, cereal, fruit, and vegetable fibre intakes were estimated from dietary questionnaires at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models stratified by age, sex, and centre, and adjusted for total energy intake, body mass index, physical activity, smoking, education, menopausal status, hormone replacement therapy, oral contraceptive use, and intakes of alcohol, folate, red and processed meats, and calcium. After multivariable adjustments, total dietary fibre was inversely associated with colorectal cancer (HR per 10 g/day increase in fibre 0.87, 95% CI: 0.79-0.96). Similar linear associations were observed for colon and rectal cancers. The association between total dietary fibre and risk of colorectal cancer risk did not differ by age, sex, or anthropometric, lifestyle, and dietary variables. Fibre from cereals and fibre from fruit and vegetables were similarly associated with colon cancer; but for rectal cancer, the inverse association was only evident for fibre from cereals. Conclusions/Significance: Our results strengthen the evidence for the role of high dietary fibre intake in colorectal cancer prevention.
Fruit and vegetable consumption and risk of aggressive and non-aggressive urothelial cell carcinomas in the European prospective investigation into cancer and nutrition
Ros, M. ; Bueno-de-Mesquita, H.B. ; Kampman, E. ; Büchner, F.L. ; Aben, K.K. ; Egevad, L. ; Overvad, K. ; Tjonneland, A. ; Roswall, N. ; Clavel-Chapelon, F. ; Boutron-Ruault, M.C. ; Moiros, S. ; Kaaks, R. ; Teucher, B. ; Weikert, S. ; Ruesten, A.V. ; Trichopoulou, A. ; Naska, A. ; Benetou, V. ; Saieva, C. ; Pala, V. ; Ricceri, F. ; Tumino, R. ; Mattiello, A. ; Peeters, P.H.M. ; Gils, C.H. van; Gram, I.T. ; Engeset, D. ; Chirlaque, M.D. ; Ardanazx, E. ; Rodriguez, L. - \ 2012
European Journal of Cancer 48 (2012)17. - ISSN 0959-8049 - p. 3267 - 3277.
bladder-cancer - vitamin-c - prospective cohort - carotenoids - smoking - diet - carcinogenesis - prevention - nutrient - folate
Background - Many epidemiological studies have examined fruit and vegetable consumption in relation to the risk of urothelial cell carcinoma (UCC) of the bladder, but results are inconsistent. The association between fruit and vegetable consumption and UCC risk may vary by bladder tumour aggressiveness. Therefore, we examined the relation between fruit and vegetable consumption and the risk of aggressive and non-aggressive UCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods - After 8.9 years of follow-up, 947 UCC were diagnosed among 468,656 EPIC participants. Of these, 421 could be classified as aggressive UCC and 433 as non-aggressive UCC cases. At recruitment, fruit and vegetable consumption was assessed by validated dietary questionnaires. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for smoking status, duration and intensity of smoking, and energy intake. Results - Total consumption of fruits and vegetables was not associated with aggressive UCC nor with non-aggressive UCC. A 25 g/day increase in leafy vegetables and grapes consumption was associated with a reduced risk of non-aggressive UCC (hazard ratio (HR) 0.88; 95% confidence interval (CI) 0.78–1.00 and HR 0.87; 95% CI 0.77–0.98, respectively), while the intake of root vegetables was inversely associated with risk of aggressive UCC (HR 0.87; 95% CI 0.77–0.98). Conclusion - Our study did not confirm a protective effect of total fruit and/or vegetable consumption on aggressive or non-aggressive UCC. High consumption of certain types of vegetables and of fruits may reduce the risk of aggressive or non-aggressive UCC; however chance findings cannot be excluded.
Educational level and risk of colorectal cancer in EPIC with specific reference to tumor location
Leufkens, A.M. ; Duijnhoven, F.J.B. van; Boshuizen, H.C. ; Sierseman, P.D. ; Kunst, A.E. ; Mouw, T. ; Tjonneland, A. ; Olsen, A. ; Overvad, K. ; Boutron-Ruault, M.C. ; Clavel-Chapelon, F. ; Morois, S. ; Krogh, V. ; Tumino, R. ; Panico, S. ; Polidoro, S. ; Palli, D. ; Kaaks, R. ; Teucher, B. ; Pischon, T. ; Trichopoulou, A. ; Orfanos, P. ; Goufa, I. ; Peeters, P.H. ; Skeie, G. ; Braaten, T. ; Rodriguez, L. ; Lujan-Barroso, L. ; Sanchez-Perez, M.J. ; Navarro, C. ; Barricarte, A. ; Zackrisson, S. ; Almquist, M. ; Hallmans, G. ; Palmqvist, R. ; Tsilidis, K.K. ; Khaw, K.T. ; Wareham, N. ; Gallo, V. ; Jenab, M. ; Riboli, E. ; Bueno-de-Mesquita, H.B. - \ 2012
International Journal of Cancer 130 (2012)3. - ISSN 0020-7136 - p. 622 - 630.
socioeconomic-status - united-states - nutrition - colon - survival - health - women - inequalities - deprivation - rectum
Existing evidence is inconclusive on whether socioeconomic status (SES) and educational inequalities influence colorectal cancer (CRC) risk, and whether low or high SES/educational level is associated with developing CRC. The aim of our study was to investigate the relationship between educational level and CRC. We studied data from 400,510 participants in the EPIC (European Prospective Investigation into Cancer and Nutrition) study, of whom 2,447 developed CRC (colon: 1,551, rectum: 896, mean follow-up 8.3 years). Cox proportional hazard regression analysis stratified by age, gender and center, and adjusted for potential confounders were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI). Relative indices of inequality (RII) for education were estimated using Cox regression models. We conducted separate analyses for tumor location, gender and geographical region. Compared with participants with college/university education, participants with vocational secondary education or less had a nonsignificantly lower risk of developing CRC. When further stratified for tumor location, adjusted risk estimates for the proximal colon were statistically significant for primary education or less (HR 0.73, 95%CI 0.57–0.94) and for vocational secondary education (HR 0.76, 95%CI 0.58–0.98). The inverse association between low education and CRC risk was particularly found in women and Southern Europe. These associations were statistically significant for CRC, for colon cancer and for proximal colon cancer. In conclusion, CRC risk, especially in the proximal colon, is lower in subjects with a lower educational level compared to those with a higher educational level. This association is most pronounced in women and Southern Europe
Variety in vegetable and fruit consumption and the risk of gastric and esophageal cancer in the European prospective investigation into cancer and nutrition
Jeurnink, S.M. ; Büchner, F.L. ; Bueno-de Mesquita, H.B. ; Siersema, P.D. ; Boshuizen, H.C. ; Numans, M.E. ; Dahm, C.C. ; Overvad, K. ; Tjonneland, A. ; Roswall, N. ; Clavel-Chapelon, F. ; Boutron-Ruault, M.C. ; Morois, S. ; Kaaks, R. ; Teucher, B. ; Boeing, H. ; Buijsse, B. ; Trichopoulou, A. ; Benetou, V. ; Zylis, D. ; Palli, D. ; Sieri, S. ; Vineis, P. ; Tumino, R. ; Panico, S. ; Ocké, M.C. ; Peeters, P.H. ; Skeie, G. ; Brustad, M. ; Lund, E. ; Sanchez-Cantalejo, E. ; Navarro, C. ; Amiano, P. ; Ardanaz, E. ; Ramón Quirós, J. ; Hallmans, G. ; Johansson, I. ; Lindkvist, B. ; Regnér, S. ; Khaw, K.T. ; Wareham, N. ; Key, T.J. ; Slimani, N. ; Norat, T. ; Vergnaud, A.C. ; Romaguera, D. ; Gonzalez, C.A. - \ 2012
International Journal of Cancer 131 (2012)6. - ISSN 0020-7136 - p. E963 - E973.
epic-eurgast - epidemiologic evidence - helicobacter-pylori - physical-activity - diet diversity - cereal fiber - vitamin-c - stomach - adenocarcinomas - metaanalysis
Diets high in vegetables and fruits have been suggested to be inversely associated with risk of gastric cancer. However, the evidence of the effect of variety of consumption is limited. We therefore investigated whether consumption of a variety of vegetables and fruit is associated with gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition study. Data on food consumption and follow-up on cancer incidence were available for 452,269 participants from 10 European countries. After a mean follow-up of 8.4 years, 475 cases of gastric and esophageal adenocarcinomas (180 noncardia, 185 cardia, gastric esophageal junction and esophagus, 110 not specified) and 98 esophageal squamous cell carcinomas were observed. Diet Diversity Scores were used to quantify the variety in vegetable and fruit consumption. We used multivariable Cox proportional hazard models to calculate risk ratios. Independent from quantity of consumption, variety in the consumption of vegetables and fruit combined and of fruit consumption alone were statistically significantly inversely associated with the risk of esophageal squamous cell carcinoma (continuous hazard ratio per 2 products increment 0.88; 95% CI 0.79–0.97 and 0.76; 95% CI 0.62–0.94, respectively) with the latter particularly seen in ever smokers. Variety in vegetable and/or fruit consumption was not associated with risk of gastric and esophageal adenocarcinomas. Independent from quantity of consumption, more variety in vegetable and fruit consumption combined and in fruit consumption alone may decrease the risk of esophageal squamous cell carcinoma. However, residual confounding by lifestyle factors cannot be excluded
A risk model for lung cancer incidence
Hoggart, C. ; Brennan, P. ; Tjonneland, A. ; Vogel, U. ; Overvad, K. ; Ostergaard, J.N. ; Kaaks, R. ; Canzian, F. ; Boeing, H. ; Steffen, A. ; Trichopoulou, A. ; Bamia, C. ; Trichopoulos, D. ; Johansson, M. ; Palli, D. ; Krogh, V. ; Tumino, R. ; Sacerdote, C. ; Panico, S. ; Boshuizen, H.C. ; Bueno-de-Mesquita, H.B. ; Peeters, P.H. ; Lund, E. ; Gram, I.T. ; Braaten, T. ; Rodrígues, L. ; Agudo, A. ; Sánchez-Cantalejo, E. ; Arriola, L. ; Chirlaque, M.D. ; Barricarte, A. ; Rasmuson, T. ; Khaw, K.T. ; Wareham, N. ; Allen, N.E. ; Riboli, E. ; Vineis, P. - \ 2012
Cancer Prevention Research / American Association for Cancer Research 5 (2012)6. - ISSN 1940-6207 - p. 834 - 846.
body-mass index - susceptibility locus - smoking-cessation - cigarette-smoking - prediction model - smokers - mortality - women - association - 5p15.33
Risk models for lung cancer incidence would be useful for prioritizing individuals for screening and participation in clinical trials of chemoprevention. We present a risk model for lung cancer built using prospective cohort data from a general population which predicts individual incidence in a given time period. We build separate risk models for current and former smokers using 169,035 ever smokers from the multicenter European Prospective Investigation into Cancer and Nutrition (EPIC) and considered a model for never smokers. The data set was split into independent training and test sets. Lung cancer incidence was modeled using survival analysis, stratifying by age started smoking, and for former smokers, also smoking duration. Other risk factors considered were smoking intensity, 10 occupational/environmental exposures previously implicated with lung cancer, and single-nucleotide polymorphisms at two loci identified by genome-wide association studies of lung cancer. Individual risk in the test set was measured by the predicted probability of lung cancer incidence in the year preceding last follow-up time, predictive accuracy was measured by the area under the receiver operator characteristic curve (AUC). Using smoking information alone gave good predictive accuracy: the AUC and 95% confidence interval in ever smokers was 0.843 (0.810-0.875), the Bach model applied to the same data gave an AUC of 0.775 (0.737-0.813). Other risk factors had negligible effect on the AUC, including never smokers for whom prediction was poor. Our model is generalizable and straightforward to implement. Its accuracy can be attributed to its modeling of lifetime exposure to smoking.
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