umu.sePublications
Change search
Refine search result
12 1 - 50 of 84
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Aglago, Elom K.
    et al.
    Huybrechts, Inge
    Murphy, Neil
    Casagrande, Corinne
    Nicolas, Genevieve
    Pischon, Tobias
    Fedirko, Veronika
    Severi, Gianluca
    Boutron-Ruault, Marie-Christine
    Fournier, Agnès
    Katzke, Verena
    Kühn, Tilman
    Olsen, Anja
    Tjønneland, Anne
    Dahm, Christina C.
    Overvad, Kim
    Lasheras, Cristina
    Agudo, Antonio
    Sánchez, Maria-Jose
    Amiano, Pilar
    Huerta, José Maria
    Ardanaz, Eva
    Perez-Cornago, Aurora
    Trichopoulou, Antonia
    Karakatsani, Anna
    Martimianaki, Georgia
    Palli, Domenico
    Pala, Valeria
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Bueno-de-Mesquita, Bas
    May, Anne
    Derksen, Jeroen W. G.
    Hellstrand, Sophie
    Ohlsson, Bodil
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Skeie, Guri
    Brustad, Magritt
    Weiderpass, Elisabete
    Cross, Amanda J.
    Ward, Heather
    Riboli, Elio
    Norat, Teresa
    Chajes, Veronique
    Gunter, Marc J.
    Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort2019In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs.

    RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026).

    CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

  • 2. Aleksandrova, Krasimira
    et al.
    Jenab, Mazda
    Leitzmann, Michael
    Bueno-de-Mesquita, Bas
    Kaaks, Rudolf
    Trichopoulou, Antonia
    Bamia, Christina
    Lagiou, Pagona
    Rinaldi, Sabina
    Freisling, Heinz
    Carayol, Marion
    Pischon, Tobias
    Drogan, Dagmar
    Weiderpass, Elisabete
    Jakszyn, Paula
    Overvad, Kim
    Dahm, Christina C.
    Tjonneland, Anne
    Bouton-Ruault, Marie-Christine
    Kuehn, Tilman
    Peppa, Eleni
    Valanou, Elissavet
    La Vecchia, Carlo
    Palli, Domenico
    Panico, Salvatore
    Sacerdote, Carlotta
    Agnoli, Claudia
    Tumino, Rosario
    May, Anne
    van Vulpen, Jonna
    Borch, Kristin Benjaminsen
    Oyeyemi, Sunday Oluwafemi
    Ramon Quiros, J.
    Bonet, Catalina
    Sanchez, Maria-Jose
    Dorronsoro, Miren
    Navarro, Carmen
    Barricarte, Aurelio
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Key, Timothy J.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Assi, Nada
    Ward, Heather A.
    Aune, Dagfinn
    Riboli, Elio
    Boeing, Heiner
    Physical activity, mediating factors and risk of colon cancer: insights into adiposity and circulating biomarkers from the EPIC cohort2017In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 46, no 6, p. 1823-1835Article in journal (Refereed)
    Abstract [en]

    There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer. We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline. High physical activity was associated with a lower risk of colon cancer: relative risk a parts per thousand<yen>91 MET-h/week vs < 91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to 0.96]. In mediation analyses, this association was accounted for by waist circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5-hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and 23% (95% CI: 6%; 111%) of the association, respectively. Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.

  • 3. Benetou, Vassiliki
    et al.
    Orfanos, Philippos
    Benetos, Ioannis S
    Pala, Valeria
    Evangelista, Alberto
    Frasca, Graziella
    Giurdanella, Maria Concetta
    Peeters, Petra HM
    van der Schouw, Yvonne T
    Rohrmann, Sabine
    Linseisen, Jakob
    Boeing, Heiner
    Weikert, Cornelia
    Pettersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bueno-de-Mesquita, H Bas
    Altzibar, Jone
    Boffetta, Paolo
    Trichopoulou, Antonia
    Anthropometry, physical activity and hip fractures in the elderly2011In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 42, no 2, p. 188-193Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Hip fractures constitute a major and growing public health problem amongst the elderly worldwide. We examined the association of anthropometry and physical activity with hip fracture incidence in a cohort of elderly Europeans, participants in the European Prospective Investigation into Cancer and nutrition (EPIC) study.

    MATERIALS AND METHODS: The study population consisted of 27982 volunteers (10553 men and 17429 women) aged 60 years and above from five European countries. Information on anthropometry, physical activity, medical history and other characteristics was collected at baseline. During a median follow-up of 8 years, 261 incident hip fractures (203 women and 58 men) were recorded. Data were analysed through Cox proportional hazard regression with adjustment for potential confounders.

    RESULTS: A higher body mass index (BMI) was associated with lower hip fracture risk (hazard ratio (HR) per increasing sex-specific-quintile: 0.85, 95% confidence interval (95% CI): 0.77-0.94). Body height was associated with increased hip fracture risk (HR per 5cm: 1.13, 95% CI: 1.01-1.25). Waist-to-hip ratio was not related to hip fracture risk. Increasing levels of leisure-time physical activity were related to lower risk (HR per increasing tertile: 0.84, 95% CI: 0.70-0.99, p for trend: 0.039).

    CONCLUSIONS: In a prospective cohort study of elderly Europeans, we found evidence that high body stature increased and high BMI decreased the incidence of hip fractures. After adjustment for BMI, waist-to-hip ratio was not associated with hip fracture risk. Leisure-time physical activity appears to play a beneficial role in the prevention of hip fractures.

  • 4. Bien, Stephanie A.
    et al.
    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.
    Bezieau, Stephane
    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
    Kuehn, Tilman
    Kury, Sebastien
    Lejbkowicz, Flavio
    Le Marchand, Loic
    Milne, Roger L.
    Li, Li
    Li, Christopher I.
    Lindblom, Annika
    Lindor, Noralane M.
    Martin, 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, Nuria
    Schafmayer, Clemens
    Scacheri, Peter C.
    Schmit, Stephanie L.
    Severi, Gianluca
    Slattery, Martha L.
    Smith, Joshua D.
    Trichopoulou, Antonia
    Tumino, Rosario
    Ulrich, Cornelia M.
    van Duijnhoven, Franzel J. B.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, USA.
    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
    Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer2019In: Human Genetics, ISSN 0340-6717, E-ISSN 1432-1203, Vol. 138, no 4, p. 307-326Article in journal (Refereed)
    Abstract [en]

    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 FDR0.2 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=2.2x10(-4), replication P=0.01), and PYGL (discovery P=2.3x10(-4), replication P=6.7x10(-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.

  • 5.
    Bodén, Stina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Myte, Robin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Shivappa, Nitin
    Hébert, James R
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Nilsson, Lena Maria
    Umeå University, Arctic Research Centre at Umeå University. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    The inflammatory potential of diet in determining cancer risk: a prospective investigation of two dietary pattern scores2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 4, article id e0214551Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Inflammation-related mechanisms may contribute to the link between diet and cancer. We sought to investigate the inflammatory impact of diet on cancer risk using the Dietary inflammatory index (DII) and an adapted Mediterranean diet score (MDS).

    METHODS: This population-based, prospective cohort study used self-reported dietary data from the Västerbotten Intervention Programme, including 100,881 participants, of whom 35,393 had repeated measures. Associations between dietary patterns and cancer risk were evaluated using Cox proportional hazards regression. We also used restricted cubic splines to test for potential non-linear associations.

    RESULTS: A total of 9,250 incident cancer cases were diagnosed during a median follow-up of 15 years. The two dietary patterns were moderately correlated to each other and had similar associations with cancer risk, predominantly lung cancer in men (DII per tertile decrease: Hazard ratio (HR) 0.81 (0.66-0.99), MDS per tertile increase: HR 0.86 (0.72-1.03)), and gastric cancer in men (DII: 0.73 (0.53-0.99), MDS: 0.73 (0.56-0.96)). Associations were, in general, found to be linear. We found no longitudinal association between 10-year change in diet and cancer risk.

    CONCLUSION: We confirm small, but consistent and statistically significant associations between a more anti-inflammatory or healthier diet and reduced risk of cancer, including a lower risk of lung and gastric cancer in men. The dietary indexes produced similar associations with respect to the risk of cancer.

  • 6.
    Bodén, Stina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Shivappa, Nitin
    Hebert, James R
    Nilsson, Lena Maria
    Umeå University, Arctic Research Centre at Umeå University. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Dietary inflammatory index and risk of first myocardial infarction: a prospective population-based study2017In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 16, article id 21Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Chronic, low-grade inflammation is an established risk factor for cardiovascular disease. The inflammatory impact of diet can be reflected by concentrations of inflammatory markers in the bloodstream and the inflammatory potential of diet can be estimated by the dietary inflammatory index (DII(TM)), which has been associated with cardiovascular disease risk in some previous studies. We aimed to examine the association between the DII and the risk of first myocardial infarction (MI) in a population-based study with long follow-up.

    METHOD: We conducted a prospective case-control study of 1389 verified cases of first MI and 5555 matched controls nested within the population-based cohorts of the Northern Sweden Health and Disease Study (NSHDS), of which the largest is the ongoing Västerbotten Intervention Programme (VIP) with nearly 100 000 participants during the study period. Median follow-up from recruitment to MI diagnosis was 6.4 years (6.2 for men and 7.2 for women). DII scores were derived from a validated food frequency questionnaire (FFQ) administered in 1986-2006. Multivariable conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI), using quartile 1 (most anti-inflammatory diet) as the reference category. For validation, general linear models were used to estimate the association between the DII scores and two inflammatory markers, high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) in a subset (n = 605) of the study population.

    RESULTS: Male participants with the most pro-inflammatory DII scores had an increased risk of MI [ORQ4vsQ1 = 1.57 (95% CI 1.21-2.02) P trend = 0.02], which was essentially unchanged after adjustment for potential confounders, including cardiovascular risk factors [ORQ4vsQ1 = 1.50 (95% CI 1.14-1.99), P trend = 0.10]. No association was found between DII and MI in women. An increase of one DII score unit was associated with 9% higher hsCRP (95% CI 0.03-0.14) and 6% higher IL-6 (95% CI 0.02-0.11) in 605 controls with biomarker data available.

    CONCLUSION: A pro-inflammatory diet was associated with an elevated risk of first myocardial infarction in men; whereas for women the relationship was null. Consideration of the inflammatory impact of diet could improve prevention of cardiovascular disease.

  • 7.
    Dahlin, Anna M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Henriksson, Maria L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor2011In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 24, p. 671-682Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to relate the density of tumor infiltrating T cells to cancer-specific survival in colorectal cancer, taking into consideration the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) screening status. The T-cell marker CD3 was stained by immunohistochemistry in 484 archival tumor tissue samples. T-cell density was semiquantitatively estimated and scored 1-4 in the tumor front and center (T cells in stroma), and intraepithelially (T cells infiltrating tumor cell nests). Total CD3 score was calculated as the sum of the three CD3 scores (range 3-12). MSI screening status was assessed by immunohistochemistry. CIMP status was determined by quantitative real-time PCR (MethyLight) using an eight-gene panel. We found that patients whose tumors were highly infiltrated by T cells (total CD3 score ≥7) had longer survival compared with patients with poorly infiltrated tumors (total CD3 score ≤4). This finding was statistically significant in multivariate analyses (multivariate hazard ratio, 0.57; 95% confidence interval, 0.31-1.00). Importantly, the finding was consistent in rectal cancer patients treated with preoperative radiotherapy. Although microsatellite unstable tumor patients are generally considered to have better prognosis, we found no difference in survival between microsatellite unstable and microsatellite stable (MSS) colorectal cancer patients with similar total CD3 scores. Patients with MSS tumors highly infiltrated by T cells had better prognosis compared with intermediately or poorly infiltrated microsatellite unstable tumors (log rank P=0.013). Regarding CIMP status, CIMP-low was associated with particularly poor prognosis in patients with poorly infiltrated tumors (multivariate hazard ratio for CIMP-low versus CIMP-negative, 3.07; 95% confidence interval, 1.53-6.15). However, some subset analyses suffered from low power and are in need of confirmation by independent studies. In conclusion, patients whose tumors are highly infiltrated by T cells have a beneficial prognosis, regardless of MSI, whereas the role of CIMP status in this context is less clear.

  • 8.
    Dahlin, Anna M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Henriksson, Maria L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jacobsson, Maria
    Eklöf, Vincy
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    The role of the CpG island methylator phenotype in colorectal cancer prognosis depends on microsatellite instability screening status2010In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 16, no 6, p. 1845-1855Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to relate the CpG island methylator phenotype (CIMP; characterized by extensive promoter hypermethylation) to cancer-specific survival in colorectal cancer, taking into consideration relevant clinicopathologic factors, such as microsatellite instability (MSI) screening status and the BRAF V600E mutation.

    EXPERIMENTAL DESIGN: Archival tumor samples from 190 patients from the Northern Sweden Health and Disease Study (NSHDS) and 414 patients from the Colorectal Cancer in Umeå Study (CRUMS), including 574 with cancer-specific survival data, were analyzed for an eight-gene CIMP panel using quantitative real-time PCR (MethyLight). MSI screening status was assessed by immunohistochemistry.

    RESULTS: CIMP-low patients had a shorter cancer-specific survival compared with CIMP-negative patients (multivariate hazard ratio in NSHDS, 2.01; 95% confidence interval, 1.20-3.37; multivariate hazard ratio in CRUMS, 1.48; 95% confidence interval, 1.00-2.22). This result was similar in subgroups based on MSI screening status and was statistically significant in microsatellite stable (MSS) tumors in NSHDS. For CIMP-high patients, a shorter cancer-specific survival compared with CIMP-negative patients was observed in the MSS subgroup. Statistical significance was lost after adjusting for the BRAF mutation, but the main findings were generally unaffected.

    CONCLUSIONS: In this study, we found a poor prognosis in CIMP-low patients regardless of MSI screening status, and in CIMP-high patients with MSS. Although not consistently statistically significant, these results were consistent in two separate patient groups and emphasize the potential importance of CIMP and MSI status in colorectal cancer research.

  • 9.
    Dahlin, Anna M
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Plasma vitamin B12 concentrations and the risk of colorectal cancer: a nested case-referent study2008In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 32, no 2, p. 304-314Article in journal (Refereed)
    Abstract [en]

    In this nested case-referent study, we related plasma concentrations of vitamin B12 to the risk of colorectal cancer, taking into consideration prediagnostic plasma folate and total homocysteine concentrations. Subjects were 226 cases and double matched referents from the population-based Northern Sweden Health and Disease Study. Follow-up times from recruitment to diagnosis ranged from 0.1 to 12.7 years, with a median of 4.2 years. Plasma vitamin B12 concentrations were inversely associated with the risk of rectal cancer: univariate odds ratio for the highest versus lowest quintile 0.34 (95% confidence interval (95% CI) 0.13-0.83), p(trend) = 0.004. Risk estimates were attenuated slightly but remained statistically significant after adjustment for body mass index, current smoking, recreational and occupational physical activity, alcohol intake and prediagnostic plasma folate and total homocysteine concentrations: OR 0.30 (95% CI 0.08-0.99), p(trend) = 0.025. The corresponding univariate and fully adjusted odds ratios for colon cancer were 1.25 (CI 0.66-2.36), p(trend) = 0.185 and 1.42 (CI 0.67-3.05), p(trend) = 0.113, respectively. The observed over-risk was attributable to left-sided colon cancer. Interaction analyses including vitamin B12, folate and homocysteine were in line with the results for vitamin B12 alone. In conclusion, these results suggest that increasing levels of plasma vitamin B12, alone or together with other factors involved in one-carbon metabolism, may reduce the risk of rectal cancer, whereas for colon cancer, the association appears to be less clear.

  • 10. de Batlle, J.
    et al.
    Ferrari, P.
    Chajes, V.
    Park, J. Y.
    Slimani, N.
    McKenzie, F.
    Overvad, K.
    Roswall, N.
    Tjønneland, A.
    Boutron-Ruault, M. C.
    Clavel-Chapelon, F.
    Fagherazzi, G.
    Katzke, V.
    Kaaks, R.
    Bergmann, M. M.
    Trichopoulou, A.
    Lagiou, P.
    Trichopoulos, D.
    Palli, D.
    Sieri, S.
    Panico, S.
    Tumino, R.
    Vineis, P.
    Bueno-de-Mesquita, H. B.
    Peeters, P. H.
    Hjartåker, A.
    Engeset, D.
    Weiderpass, E.
    Sánchez, S.
    Travier, N.
    Sanchez, M. J.
    Amiano, P.
    Chirlaque, M. D.
    Barricarte Gurrea, A.
    Khaw, K. T.
    Key, T. J.
    Bradbury, K. E.
    Ericson, U.
    Sonestedt, E.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    Riboli, E.
    Romieu, I.
    Dietary folate intake and breast cancer risk: European prospective investigation into cancer and nutrition2015In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 107, no 1, article id dju367Article in journal (Refereed)
    Abstract [en]

    There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided. A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P (trend) = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, P (trend) = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P (trend) = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (> 12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P (interaction) = .035). Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women.

  • 11.
    Ekblom, Kim
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wiklund, Per-Gunnar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Iron stores and HFE genotypes are not related to increased risk of ischemic stroke.: a prospective nested case-referent study2007In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 24, no 5, p. 405-411Article in journal (Refereed)
    Abstract [en]

    Background: High iron levels can increase the formation of noxious oxygen radicals, which are thought to contribute to cerebrovascular disease. The aim of this prospective study was to determine if iron status and HFE genotypes constitute risk factors for stroke.

    Methods: First-ever stroke cases (231 ischemic and 42 hemorrhagic) and matched double referents from the population-based Northern Sweden cohorts were studied in a nested case-referent setting.

    Results: For total iron binding capacity, an increased risk of ischemic stroke was seen in the highest quartile (OR 1.80; 95% CI 1.14-2.83; p for trend 0.012). The highest quartile of transferrin iron saturation showed a decreased risk of ischemic stroke in men (OR 0.44; 95% CI 0.22-0.87; p for trend 0.028), but not in women. There was an increased risk of hemorrhagic stroke in the second (OR 4.07; 95% CI 1.09-15.20) and third quartile (OR 4.22; 95% CI 1.08-16.42) of ferritin. Neither quartiles of plasma iron concentrations nor the HFE C282Y and H63D genotypes were associated with ischemic or hemorrhagic stroke.

    Conclusions: Iron stores were not positively related to increased risk of ischemic stroke. Furthermore, HFE genotypes did not influence the risk of ischemic or hemorrhagic stroke. Copyright (c) 2007 S. Karger AG, Basel.

  • 12.
    Ekblom, Kim
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Marklund, Stefan L.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Iron Biomarkers in Plasma, HFE Genotypes, and the Risk for Colorectal Cancer in a Prospective Setting2012In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 55, no 3, p. 337-344Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: High iron levels can increase the formation of noxious oxygen radicals, which are thought to promote carcinogenesis. OBJECTIVE: The aim of this prospective study was to determine whether iron biomarkers and HFE genotypes, which influence iron regulation, constitute risk factors for colorectal cancer. DESIGN: This is a prospective nested case-referent study. SETTINGS: The study was performed within the population-based Northern Sweden Health and Disease Study. PATIENTS: The study included 226 cases of colorectal cancer and 437 matched referents. MAIN OUTCOME MEASURES: Conditional regression analysis was performed. Adjustments for smoking, smoking and BMI, and HFE C282Y and H63D were performed. RESULTS: The highest quintile of total iron-binding capacity showed significantly higher risk for colorectal cancer, unadjusted OR 2.35 (95% CI 1.38-4.02). When stratified by sex, the findings were only present in women (OR 3.34 (95% CI 1.59-7.02)). Ferritin was associated with reduced risk throughout quintiles 2 to 5 both in univariate and multivariate models. LIMITATIONS: Colorectal cancer may influence iron markers because of occult bleeding. Homozygotes for HFE C282Y were too few to make conclusions for this group. The relatively short follow-up time might be insufficient to detect risk of iron biomarkers. CONCLUSIONS: High iron levels do not increase the risk of colorectal cancer. HFE genotypes influencing iron uptake had no effect on colorectal cancer risk.

  • 13.
    Eklöf, Vincy
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    The reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T polymorphisms and the risk of colorectal cancer: a nested case-referent study2008In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, no 5, p. 393-401Article in journal (Refereed)
    Abstract [en]

    Objective. Polymorphisms in genes involved in folate uptake and metabolism may affect folate status and, thereby, the risk of cancer. In this nested case‐referent study, we related two such polymorphisms, reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T, to the risk of colorectal cancer, taking into account pre‐diagnostic plasma folate and total homocysteine concentrations and the MTHFR 677C>T polymorphism, which were analysed in a previous study.

    Material and methods. Subjects were 220 cases and 414 matched referents from the population‐based Northern Sweden Health and Disease Study.

    Results. The RFC1 80A‐allele was associated with reduced plasma folate and elevated plasma total homocysteine concentrations, but the result was statistically significant only for folate. In contrast, the FOLH1 1561T‐allele was associated with higher plasma folate and reduced plasma total homocysteine concentrations, and the result was statistically significant only for homocysteine. Neither polymorphism was related to the risk of colorectal cancer, either in univariate analysis or after adjusting for body mass index, current smoking, recreational and occupational physical activity and alcohol intake. Further adjustment for folate or homocysteine status or the MTHFR 677C>T polymorphism did not affect risk estimates. Subjects with the RFC1 80AA genotype in combination with low plasma folate concentrations or the MTHFR 677TT genotype had a reduced risk of colorectal cancer of borderline statistical significance.

    Conclusions. These findings suggest that although the RFC1 80G>A and FOLH1 1561C>T polymorphisms may influence folate status, they are not likely to have a major independent role in the development of colorectal cancer.

    Read More: http://informahealthcare.com/doi/abs/10.1080/00365510701805431

  • 14. Eussen, Simone JPM
    et al.
    Nilsen, Roy M
    Midttun, Oivind
    Hustad, Steinar
    IJssennagger, Noortje
    Meyer, Klaus
    Fredriksen, Ase
    Ulvik, Arve
    Ueland, Per M
    Brennan, Paul
    Johansson, Mattias
    Bueno-de-Mesquita, Bas
    Vineis, Paolo
    Chuang, Shu-Chun
    Boutron-Ruault, Marie Christine
    Dossus, Laure
    Perquier, Florence
    Overvad, Kim
    Teucher, Birgit
    Grote, Verena A
    Trichopoulou, Antonia
    Adarakis, George
    Plada, Maria
    Sieri, Sabina
    Tumino, Rosario
    Santucci de Magistris, Maria
    Ros, Martine M
    Peeters, Petra HM
    Luisa Redondo, Maria
    Zamora-Ros, Raul
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Sonestedt, Emily
    Ericson, Ulrika
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Pharmacology.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wark, Petra A
    Gallo, Valentina
    Norat, Teresa
    Riboli, Elio
    Vollset, Stein Emil
    North-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) Study2013In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 110, no 2, p. 363-374Article in journal (Refereed)
    Abstract [en]

    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 B-2 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 B-6 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.

  • 15. Eussen, Simone JPM
    et al.
    Vollset, Stein Emil
    Hustad, Steinar
    Midttun, Øivind
    Meyer, Klaus
    Fredriksen, Ase
    Ueland, Per Magne
    Jenab, Mazda
    Slimani, Nadia
    Boffetta, Paolo
    Overvad, Kim
    Thorlacius-Ussing, Ole
    Tjønneland, Anne
    Olsen, Anja
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Morois, Sophie
    Weikert, Cornelia
    Pischon, Tobias
    Linseisen, Jakob
    Kaaks, Rudolf
    Trichopoulou, Antonia
    Zilis, Demosthenes
    Katsoulis, Michael
    Palli, Domenico
    Pala, Valeria
    Vineis, Paolo
    Tumino, Rosario
    Panico, Salvatore
    Peeters, Petra HM
    Bueno-de-Mesquita, H Bas
    van Duijnhoven, Fränzel JB
    Skeie, Guri
    Muñoz, Xavier
    Martínez, Carmen
    Dorronsoro, Miren
    Ardanaz, Eva
    Navarro, Carmen
    Rodríguez, Laudina
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Manjer, Jonas
    Ericson, Ulrika
    Bingham, Sheila
    Khaw, Kay-Tee
    Norat, Teresa
    Riboli, Elio
    Plasma vitamins B2, B6, and B12, and related genetic variants as predictors of colorectal cancer risk2010In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, no 10, p. 2549-2561Article in journal (Refereed)
    Abstract [en]

    This European population-based study is the first to indicate that vitamin B2 is inversely associated with colorectal cancer, and is in agreement with previously suggested inverse associations of vitamin B6 with colorectal cancer.

  • 16. Eussen, Simone JPM
    et al.
    Vollset, Stein Emil
    Igland, Jannicke
    Meyer, Klaus
    Fredriksen, Ase
    Ueland, Per Magne
    Jenab, Mazda
    Slimani, Nadia
    Boffetta, Paolo
    Overvad, Kim
    Tjønneland, Anne
    Olsen, Anja
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Morois, Sophie
    Weikert, Cornelia
    Pischon, Tobias
    Linseisen, Jakob
    Kaaks, Rudolf
    Trichopoulou, Antonia
    Zilis, Demosthenes
    Katsoulis, Michael
    Palli, Domenico
    Berrino, Franco
    Vineis, Paolo
    Tumino, Rosario
    Panico, Salvatore
    Peeters, Petra HM
    Bueno-de-Mesquita, H Bas
    van Duijnhoven, Fränzel JB
    Gram, Inger Torhild
    Skeie, Guri
    Lund, Eiliv
    González, Carlos A
    Martínez, Carmen
    Dorronsoro, Miren
    Ardanaz, Eva
    Navarro, Carmen
    Rodríguez, Laudina
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Manjer, Jonas
    Ericson, Ulrika
    Bingham, Sheila
    Khaw, Kay-Tee
    Norat, Teresa
    Riboli, Elio
    Plasma folate, related genetic variants, and colorectal cancer risk in EPIC2010In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 19, no 5, p. 1328-1340Article in journal (Refereed)
    Abstract [en]

    Findings of the present study tend to weaken the evidence that folate plays an important role in CRC carcinogenesis. However, larger sample sizes are needed to adequately address potential gene-environment interactions.

  • 17. Ferrari, Pietro
    et al.
    Jenab, Mazda
    Norat, Teresa
    Moskal, Aurelie
    Slimani, Nadia
    Olsen, Anja
    Tjønneland, Anne
    Overvad, Kim
    Jensen, Majken K
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Morois, Sophie
    Rohrmann, Sabine
    Linseisen, Jakob
    Boeing, Heiner
    Bergmann, Manuela
    Kontopoulou, Dimitra
    Trichopoulou, Antonia
    Kassapa, Christina
    Masala, Giovanna
    Krogh, Vittorio
    Vineis, Paolo
    Panico, Salvatore
    Tumino, Rosario
    van Gils, Carla H
    Peeters, Petra
    Bueno-de-Mesquita, H Bas
    Ocké, Marga C
    Skeie, Guri
    Lund, Eiliv
    Agudo, Antonio
    Ardanaz, Eva
    López, Dolores C
    Sanchez, Maria-Jose
    Quirós, José R
    Amiano, Pilar
    Berglund, Göran
    Manjer, Jonas
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Allen, Naomi
    Key, Tim
    Bingham, Sheila
    Mazuir, Mathieu
    Boffetta, Paolo
    Kaaks, Rudolf
    Riboli, Elio
    Lifetime and baseline alcohol intake and risk of colon and rectal cancers in the European prospective investigation into cancer and nutrition (EPIC).2007In: Int J Cancer, ISSN 0020-7136, Vol. 121, no 9, p. 2065-72Article in journal (Refereed)
  • 18.
    Gylling, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Myte, Robin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Schneede, Jørn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Häggstrom, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ulvik, Arve
    Ueland, Per M.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Vitamin B-6 and colorectal cancer risk: a prospective population-based study using 3 distinct plasma markers of vitamin B-6 status2017In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 105, no 4, p. 897-904Article in journal (Refereed)
    Abstract [en]

    Background: Higher plasma concentrations of the vitamin B-6 marker pyridoxal 5#-phosphate (PLP) have been associated with reduced colorectal cancer (CRC) risk. Inflammatory processes, including vitamin B-6 catabolism, could explain such findings. Objective: We investigated 3 biomarkers of vitamin B-6 status in relation to CRC risk. Design: This was a prospective case-control study of 613 CRC cases and 1190 matched controls nested within the Northern Sweden Health and Disease Study (n = 114,679). Participants were followed from 1985 to 2009, and the median follow-up from baseline to CRC diagnosis was 8.2 y. PLP, pyridoxal, pyridoxic acid (PA), 3-hydroxykynurenine, and xanthurenic acids (XAs) were measured in plasma with the use of liquid chromatography-tandem mass spectrometry. We calculated relative and absolute risks of CRC for PLP and the ratios 3-hydroxykynurenine: XA (HK: XA), an inverse marker of functional vitamin B-6 status, and PA:(PLP + pyridoxal) (PAr), a marker of inflammation and oxidative stress and an inverse marker of vitamin B-6 status. Results: Plasma PLP concentrations were associated with a reduced CRC risk for the third compared with the first quartile and for PLP sufficiency compared with deficiency [OR: 0.60 (95% CI: 0.44, 0.81) and OR: 0.55 (95% CI: 0.37, 0.81), respectively]. HK: XA and PAr were both associated with increased CRC risk [OR: 1.48 (95% CI: 1.08, 2.02) and OR: 1.50 (95% CI: 1.10, 2.04), respectively] for the fourth compared with the first quartile. For HK: XA and PAr, the findings were mainly observed in study participants with,10.5 y of follow-up between sampling and diagnosis. Conclusions: Vitamin B-6 deficiency as measured by plasma PLP is associated with a clear increase in CRC risk. Furthermore, our analyses of novel markers of functional vitamin B-6 status and vitamin B-6-associated oxidative stress and inflammation suggest a role in tumor progression rather than initiation.

  • 19.
    Gylling, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Myte, Robin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Ulvik, Arve
    Bevital AS, Laboratory building, Bergen, Norway.
    Ueland, Per Magne
    Department of Clinical Science, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
    Midttun, Øivind
    Bevital AS, Laboratory building, Bergen, Norway.
    Schneede, Jørn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Häggström, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk2019In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 5, p. 68p. 947-956Article in journal (Other academic)
    Abstract [en]

    Background: One-carbon metabolism biomarker are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one-carbon metabolism branches can be assessed by relating the functional B-vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs.

    Objective: We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk.

    Design: The relative contribution of potential confounders to the variance of the ratio-based B-vitamin markers was calculated by linear regression in a nested case-control study of 613 CRC cases and 1211 matched controls. Total B-vitamin status was represented by a summary score comprising Z-standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5´-phosphate, and riboflavin. Associations with CRC risk were estimated using conditional logistic regression.

    Results: The ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. Associations with CRC risk were similar for the ratio-based B-vitamin markers and total B-vitamin status (approximately 25% lower risk for high versus low B-vitamin status).

    Conclusions: Ratio-based B-vitamin markers were good predictors of total B-vitamin status, and displayed similar associations with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice to aid interpretation of tHcy results.

  • 20.
    Gylling, Björn
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Ueland, Per Magne
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Low folate levels are associated with reduced risk of colorectal cancer in a population with low folate status2014In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 23, no 10, p. 2136-2144Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A diet rich in folate is associated with a reduced colorectal cancer risk, whereas the role of circulating levels is less clear. The aim of this study was to relate prediagnostic plasma folate, vitamin B12, and homocysteine concentrations to the risk of colorectal cancer.

    METHODS: This was a prospective case-control study of 331 cases and 662 matched controls nested within the population-based Northern Sweden Health and Disease Study. Median follow-up time from recruitment to diagnosis was 10.8 years.

    RESULTS: Plasma folate concentrations were positively related to colorectal cancer risk; multivariate odds ratios were 1.62 [95% confidence intervals (CI), 1.08-2.42] and 1.42 (95% CI, 0.94-2.21) for the middle and highest versus lowest tertile, respectively. In subjects with follow-up <10.8 years, a statistically significant doubled risk was observed for the middle and highest versus lowest tertile, whereas findings for longer follow-up times were null. A positive risk relationship was also observed for tumor stage III-IV but not I-II. Plasma vitamin B12 concentrations were inversely associated with rectal cancer risk. Homocysteine was not significantly related to colorectal cancer risk.

    CONCLUSIONS: In this population-based, nested case-control study, low plasma folate concentrations were associated with a reduced colorectal cancer risk. This protective role was mainly observed in subjects with higher tumor stage or shorter follow-up time between recruitment and diagnosis. Low circulating folate status may protect against colorectal cancer or suppress progression of preneoplastic or neoplastic lesions.

    IMPACT: These findings may have relevance for the ongoing debate about mandatory folic acid fortification of flour.

  • 21.
    Harlid, S.
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University.
    Myte, Robin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    The metabolic syndrome, inflammation and colorectal cancer risk: an evaluation of large panels of plasma protein markers using repeated, pre-diagnostic samples2017In: Mediators of Inflammation, article id 4803156Article in journal (Refereed)
    Abstract [en]

    Metabolic syndrome (MetS), a set of metabolic risk factors including obesity, dysglycemia, and dyslipidemia, is associated with increased colorectal cancer (CRC) risk. A putative biological mechanism is chronic, low-grade inflammation, both a feature of MetS and a CRC risk factor. However, excess body fat also induces a proinflammatory state and increases CRC risk. In order to explore the relationship between MetS, body size, inflammation, and CRC, we studied large panels of inflammatory and cancer biomarkers. We included 138 participants from the Västerbotten Intervention Programme with repeated sampling occasions, 10 years apart. Plasma samples were analyzed for 178 protein markers by proximity extension assay. To identify associations between plasma protein levels and MetS components, linear mixed models were fitted for each protein. Twelve proteins were associated with at least one MetS component, six of which were associated with MetS score. MetS alone was not related to any protein. Instead, BMI displayed by far the strongest associations with the biomarkers. One of the 12 MetS score-related proteins (FGF-21), also associated with BMI, was associated with an increased CRC risk (OR 1.71, 95% CI 1.19–2.47). We conclude that overweight and obesity, acting through both inflammation and other mechanisms, likely explain the MetS-CRC connection.

  • 22.
    Harlid, Sophia
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Myte, Robin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Replication of Epigenome-wide Associations Related to Body Mass Index Using the Infinium MethylationEPIC BeadChip on Repeated Samples2017In: Genetic Epidemiology, ISSN 0741-0395, E-ISSN 1098-2272, Vol. 41, no 7, p. 680-680Article in journal (Other academic)
  • 23.
    Harlid, Sophia
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Myte, Robin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    The metabolic syndrome, inflammation, and colorectal cancer risk: an evaluation of large panels of plasma protein markers using erepeated, prediagnostic samples2017In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 4803156Article in journal (Refereed)
    Abstract [en]

    Metabolic syndrome (MetS), a set of metabolic risk factors including obesity, dysglycemia, and dyslipidemia, is associated with increased colorectal cancer (CRC) risk. A putative biological mechanism is chronic, low-grade inflammation, both a feature of MetS and a CRC risk factor. However, excess body fat also induces a proinflammatory state and increases CRC risk. In order to explore the relationship between MetS, body size, inflammation, and CRC, we studied large panels of inflammatory and cancer biomarkers. We included 138 participants from the Vasterbotten Intervention Programme with repeated sampling occasions, 10 years apart. Plasma samples were analyzed for 178 protein markers by proximity extension assay. To identify associations between plasma protein levels and MetS components, linear mixed models were fitted for each protein. Twelve proteins were associated with at least one MetS component, six of which were associated with MetS score. MetS alone was not related to any protein. Instead, BMI displayed by far the strongest associations with the biomarkers. One of the 12 MetS score-related proteins (FGF-21), also associated with BMI, was associated with an increased CRC risk (OR 1.71, 95% CI 1.19-2.47). We conclude that overweight and obesity, acting through both inflammation and other mechanisms, likely explain the MetS-CRC connection.

  • 24. Harrison, Tabitha A.
    et al.
    Lu, Yiwen
    Zeng, Chenjie
    Qu, Flora
    Anderson, Kristin
    Brenner, Hermann
    Buchanan, Daniel D.
    Campbell, Peter T.
    Chan, Andrew T.
    Chang-Claude, Jenny
    Giles, Graham G.
    van Guelpen, Bethany
    Umeå University.
    Hoffmeister, Michael
    Jenkins, Mark A.
    Lindor, Noralane M.
    Milne, Roger L.
    Newcomb, Polly A.
    Nishihara, Reiko
    Woods, Michael O.
    Ogino, Shuji
    Potter, John D.
    Slattery, Martha L.
    Sun, Wei
    Thibodeau, Stephen N.
    Hsu, Li
    Peters, Ulrike
    Genome-wide association study by colorectal carcinoma subtype2018In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 78, no 13Article in journal (Other academic)
    Abstract [en]

    Over 50 genetic variants have been associated with colorectal cancer (CRC) risk through genome-wide association studies (GWAS), yet these variants represent only a fraction of the total estimated heritability. CRC is a heterogenous disease with diverse tumor etiology. Assessing genetic risk in molecular subtypes may help to identify novel loci and characterize genetic risk among tumor subtypes. We used microsatellite instability (MSI), an established CRC classifier with etiological and therapeutic relevance, to define CRC subtypes for GWAS analyses. We conducted a case-case analysis to estimate odds ratios (OR) and 95% confidence intervals (CI) for association of genome-wide variants with microsatellite stable (MSS) versus unstable (MSI) carcinomas. We ran an inverse-variance weighted fixed-effects meta-analysis across GWAS in a discovery set of 4,163 population-based CRC cases with harmonized microsatellite instability (MSI) marker and imputed genotype data. For each analysis, we used log-additive logistic regression, adjusting for age, sex, and principal components to account for population substructure. We then followed up with replication of 102 SNPs that reached p-values less than 5x10-6 in 1,698 cases. A total of 845 (20.3%) cancer cases were microsatellite unstable in the discovery population and 174 (10.2%) were unstable in the replication population. No variants reached the genome-wide significance level of 5x10-8 in the discovery set. However, we identified two variants that reached a Bonferroni corrected p-value of 4.0x10-4 in the replication set. This included one variant in MLH1 (Replication: OR=1.74, 95% CI=1.53-1.98, p=1.63x10-5; Discovery+Replication: OR=1.45, 95% CI=1.37-1.54, p=9.76x10-11) and one variant in LOC105377645 (Replication: OR=1.70, 95% CI=1.49-1.94, p=5.13x10-5; Discovery+Replication: OR=1.45, 95% CI=1.37-1.54, p=9.76 x 10-11). The MLH1 gene is a DNA mismatch repair gene implicated in Lynch Syndrome, the hallmark of which is microsatellite instability. This is the first genome-wide scan to identify a common variant in MLH1 that is associated with CRC. This variant (minor allele frequency, MAF = 23% in this all European ancestry population) is located in the 5'-untranslated region of MLH1 and is thought to act as a long-range regulator of DCLK3, a potential tumor driver gene. The second variant, located in LOC105377645 with an MAF of 22%, is in an uncharacterized region of the genome and has not previously been implicated in cancer development. These findings suggest that accounting for molecular heterogeneity is important for discovery and characterization of genetic variants associated with CRC risk. We plan to run polytomous regression analyses, increase our sample size, and further investigate CRC subtypes by CIMP, BRAF mutation, KRAS mutation status.

  • 25.
    Henriksson, Maria L
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Edin, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dahlin, Anna M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Oldenborg, Per-Arne
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Colorectal Cancer Cells Activate Adjacent Fibroblasts Resulting in FGF1/FGFR3 Signaling and Increased Invasion.2011In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 178, no 3, p. 1387-1394Article in journal (Refereed)
    Abstract [en]

    Cancer-associated fibroblasts expressing fibroblast activation protein (FAP) have been implicated in the invasive behavior of colorectal cancer. In this study, we use FAP expression as a marker of fibroblast activation and analyze the effect of activated fibroblasts on colorectal cancer migration and invasion in experimental cell studies. We also investigated the expression pattern of FAP in cancer-associated fibroblasts during transformation from benign to malignant colorectal tumors. In immunohistochemical analyses, FAP was expressed in fibroblasts in all colorectal cancer samples examined, whereas all normal colon, hyperplastic polyps, or adenoma samples were negative. In in vitro studies, conditioned medium from colon cancer cells, but not adenoma cells, activated fibroblasts by inducing FAP expression. These activated fibroblasts increased the migration and invasion of colon cancer cells in Boyden chamber experiments and in a three-dimensional cell culture model. We identify fibroblast growth factor 1/fibroblast growth factor receptor 3 (FGF1/FGFR-3) signaling as mediators leading to the increased migration and invasion. Activated fibroblasts increase their expression of FGF1, and by adding a fibroblast growth factor receptor inhibitor, as well as an FGF1-neutralizing antibody, we reduced the migration of colon cancer cells. Our findings provide evidence of a possible molecular mechanism involved in the cross talk between cancer cells and fibroblasts leading to cancer cell invasion.

  • 26. Hermann, Silke
    et al.
    Rohrmann, Sabine
    Linseisen, Jakob
    May, Anne M
    Kunst, Anton
    Besson, Herve
    Romaguera, Dora
    Travier, Noemie
    Tormo, Maria-Jose
    Molina, Esther
    Dorronsoro, Miren
    Barricarte, Aurelio
    Rodriguez, Laudina
    Crowe, Francesca L
    Khaw, Kay-Tee
    Wareham, Nicholas J
    van Boeckel, Petra Ga
    Bueno-de-Mesquita, H Bas
    Overvad, Kim
    Uhre Jakobsen, Marianne
    Tjonneland, Anne
    Halkjaer, Jytte
    Agnoli, Claudia
    Mattiello, Amalia
    Tumino, Rosario
    Masala, Giovanna
    Vineis, Paolo
    Naska, Androniki
    Orfanos, Philippos
    Trichopoulou, Antonia
    Kaaks, Rudolf
    Bergmann, Manuela M
    Steffen, Annika
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Borgquist, Signe
    Manjer, Jonas
    Braaten, Tonje
    Fagherazzi, Guy
    Clavel-Chapelon, Francoise
    Mouw, Traci
    Norat, Teresa
    Riboli, Elio
    Rinaldi, Sabina
    Slimani, Nadia
    Peeters, Petra Hm
    The association of education with body mass index and waist circumference in the EPIC-PANACEA study2011In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 11, no 1, p. 169-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine the association of education with body mass index (BMI) and waist circumference (WC) in the European Prospective Investigation into Cancer and Nutrition (EPIC).

    METHOD: This study included 141,230 male and 336,637 female EPIC-participants, who were recruited between 1992 and 2000. Education, which was assessed by questionnaire, was classified into four categories; BMI and WC, measured by trained personnel in most participating centers, were modeled as continuous dependent variables. Associations were estimated using multilevel mixed effects linear regression models.

    RESULTS: Compared with the lowest education level, BMI and WC were significantly lower for all three higher education categories, which was consistent for all countries. Women with university degree had a 2.1 kg/m2 lower BMI compared with women with lowest education level. For men, a statistically significant, but less pronounced difference was observed (1.3 kg/m2). The association between WC and education level was also of greater magnitude for women: compared with the lowest education level, average WC of women was lower by 5.2 cm for women in the highest category. For men the difference was 2.9 cm.

    CONCLUSION: In this European cohort, there is an inverse association between higher BMI as well as higher WC and lower education level. Public Health Programs that aim to reduce overweight and obesity should primarily focus on the lower educated population.

  • 27.
    Hoeft, Birgit
    et al.
    German Cancer Research Center, Heidelberg, Germany .
    Linseisen, Jakob
    German Cancer Research Center, Heidelberg, Germany .
    Beckmann, Lars
    German Cancer Research Center, Heidelberg, Germany .
    Müller-Decker, Karin
    German Cancer Research Center, Heidelberg, Germany .
    Canzian, Federico
    German Cancer Research Center, Heidelberg, Germany.
    Hüsing, Anika
    German Cancer Research Center, Heidelberg, Germany.
    Kaaks, Rudolf
    German Cancer Research Center, Heidelberg, Germany.
    Vogel, Ulla
    National Food Institute, Technical University of Denmark, Soborg, Denmark.
    Jakobsen, Marianne Uhre
    Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg, Denmark.
    Overvad, Kim
    Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg, Denmark.
    Hansen, Rikke Dalgaard
    Danish Cancer Society, Copenhagen, Denmark.
    Knüppel, Sven
    Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
    Boeing, Heiner
    Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
    Trichopoulou, Antonia
    Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece .
    Yvoni, Koumantaki
    Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece.
    Trichopoulos, Dimitrios
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA .
    Berrino, Franco
    Etiological Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy .
    Palli, Domenico
    Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy .
    Panico, Salvatore
    Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy .
    Tumino, Rosario
    Cancer Registry and Histopathology Unit, Department of Oncology , “Civile - M.P.Arezzo” Hospital, Ragusa, Italy .
    Bueno-de-Mesquita, H Bas
    National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands .
    van Duijnhoven, Fränzel J B
    National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands .
    van Gils, Carla H
    Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands .
    Peeters, Petra H
    Julius Center, University Medical Center Utrecht, Utrecht, The Netherlands .
    Dumeaux, Vanessa
    Institute of Community Medicine, University of Tromsø, Norway .
    Lund, Eiliv
    Institute of Community Medicine, University of Tromsø, Norway .
    Huerta Castaño, José M
    CIBER Epidemiología y Salud Pública, CIBERESP, Spain .
    Muñoz, Xavier
    Research Laboratory and Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain .
    Rodriguez, Laudina
    Public Health and Participation Directorate, Health and Health Care Services Council, Asturias, Spain .
    Barricarte, Aurelio
    CIBER Epidemiología y Salud Pública, CIBERESP, Spain .
    Manjer, Jonas
    Department of Surgery, Malmö University Hospital, Malmö, Sweden .
    Jirström, Karin
    Center for Molecular Pathology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, Malmö Sweden .
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Spencer, Elizabeth A
    Cancer Epidemiology Unit, University of Oxford, Oxford, UK .
    Crowe, Francesca L
    Cancer Epidemiology Unit, University of Oxford, Oxford, UK .
    Khaw, Kay-Tee
    Department of Public Health and Primary Care, University of Cambridge .
    Wareham, Nick
    Medical Research Council (MRC) Epidemiology Unit, Cambridge, UK .
    Morois, Sophie
    Inserm, (Institut National de la Santé et de la Recherche Médicale), and Institut Gustave Roussy, Villejuif, France .
    Boutron-Ruault, Marie-Christine
    Inserm, (Institut National de la Santé et de la Recherche Médicale), and Institut Gustave Roussy, Villejuif, France .
    Clavel-Chapelon, Françoise
    Inserm, (Institut National de la Santé et de la Recherche Médicale), and Institut Gustave Roussy, Villejuif, France .
    Chajes, Veronique
    International Agency for Research on Cancer (IARC), Lyon, France .
    Jenab, Mazda
    International Agency for Research on Cancer (IARC), Lyon, France .
    Boffetta, Paolo
    International Agency for Research on Cancer (IARC), Lyon, France .
    Vineis, Paolo
    Cancer Epidemiology Department, University of Turin, Turin, Italy .
    Mouw, Traci
    Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK .
    Norat, Teresa
    Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK .
    Riboli, Elio
    Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK .
    Nieters, Alexandra
    German Cancer Research Center, Heidelberg, Germany .
    Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk.2010In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 31, no 3, p. 466-472Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer is the third most common malignant tumor and the fourth-leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in depth analysis of inter-individual differences in fatty acid metabolizing genes as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. 392 single nucleotide polymorphisms were selected using pairwise tagging with an r(2) cutoff of 0.8 and a minor allele frequency of >5%. Conditional logistic regression models were used to estimate odds ratios and corresponding 95% confidence intervals. Haplotype analysis was performed using a generalized linear model framework. On the genotype level, HPGD, PLA2G6, and TRPV3 were associated with higher risk for colorectal cancer, while PTGER2 was associated with lower colorectal cancer risk. A significant inverse association (p < 0.006) was found for PTGER2 GGG haplotype while HPGD AGGAG and PLA2G3 CT haplotypes were significantly (p < 0.001 and p = 0.003, respectively) associated with higher risk of colorectal cancer. Based on these data we present for the first time the association of HPGD variants with colorectal cancer risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and colorectal cancer risk.

  • 28.
    Hultdin, Johan
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Nutritional Research.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Plasma folate, vitamin B12, and homocysteine and prostate cancer risk: a prospective study.2005In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 113, no 5, p. 819-824Article in journal (Refereed)
    Abstract [en]

    The role of folate metabolism in cancer development is a topic of much current interest, with maintenance of adequate folate status tending to show a protective effect. Aberrant methylation, primarily hypermethylation of certain genes including tumor suppressors, has been implicated in prostate cancer development. Folate, vitamin B12 and homocysteine are essential for methyl group metabolism and thus also for DNA methylation. We related plasma levels of these factors to prostate cancer risk in a prospective study of 254 case subjects and 514 matched control subjects. Increasing plasma levels of folate and vitamin B12 were statistically significantly associated with increased prostate cancer risk, with an odds ratio of 1.60 (95% CI = 1.03-2.49; p(trend) = 0.02) for folate and 2.63 (95% CI = 1.61-4.29; p(trend) < 0.001) for vitamin B12 for highest vs. lowest quartile. Increasing plasma homocysteine levels were associated with a reduced risk of borderline significance (OR = 0.67; 95% CI = 0.43-1.04; p(trend) = 0.08). After adjustment for the other 2 plasma variables, body mass index and smoking, a statistically significant increased risk remained only for vitamin B12 (OR = 2.96; 95% CI = 1.58-5.55; p(trend) = 0.001). Adjusted OR for folate and homocysteine were 1.30 (95% CI = 0.74-2.24; p(trend) = 0.17) and 0.91 (95% CI = 0.51-1.58; p(trend) = 0.60), respectively. Our results suggest that factors contributing to folate status are not protective against prostate cancer. On the contrary, vitamin B12, associated with an up to 3-fold increase in risk, and possibly also folate, may even stimulate prostate cancer development. These findings are novel and should be explored further in future studies. (c) 2004 Wiley-Liss, Inc.

  • 29.
    Hultdin, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Winkvist, Anna
    Department of Clinical Nutrition, Göteborg University, Gothenburg, Sweden.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K.
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Prospective study of first stroke in relation to plasma homocysteine and MTHFR 677C > T and 1298A > C genotypes and haplotypes: evidence for an association with hemorrhagic stroke2011In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 49, no 9, p. 1555-1562Article in journal (Refereed)
    Abstract [en]

    Background: Abnormalities in homocysteine metabolism have been suggested as risk factors for stroke. The aim of this prospective study was to examine whether total plasma homocysteine concentration (tHcy) and its main genetic determinant, methylene tetrahydrofolate reductase (MTHFR) polymorphisms, were associated with first ischemic or hemorrhagic stroke.

    Methods: This was a nested case-referent study of 321 ischemic and 60 hemorrhagic stroke cases, defined by WHO MONICA criteria and each matched with two event-free referents for sex, age, cohort, recruitment date and geographical area. All subjects were from the population-based Northern Sweden Health and Disease Study cohorts. Odds ratios were determined by conditional logistic regression.

    Results: The mean follow-up time was 4.2 years. Both tHcy and MTHFR were independent predictors of hemorrhagic stroke in multivariate models including body mass index, hypertension and, for MTHFR, tHcy [OR for the highest vs. lowest tHcy quartile 8.13 (95% CI 1.83-36.1), p(trend)=0.002; OR for MTHFR 677TT vs. 677CC genotype 3.62 (95% CI 0.77-17.0), p(trend)=0.040]. Haplotype analyses confirmed that the MTHFR 677T-1298A haplotype was positively associated with hemorrhagic stroke [OR 1.81 (95% CI 1.09-3.00), p=0.022], whereas the MTHFR 677C-1298C haplotype was not significantly related to either hemorrhagic or ischemic stroke. Neither tHcy nor the MTHFR polymorphisms were significant predictors of ischemic stroke.

    Conclusion: Both elevated plasma homocysteine levels and the MTHFR 677T allele are indicators of increased risk of hemorrhagic stroke in the northern Swedish population.

  • 30. Huyghe, Jeroen R.
    et al.
    Bien, Stephanie A.
    Harrison, Tabitha A.
    Kang, Hyun Min
    Chen, Sai
    Schmit, Stephanie L.
    Conti, David V.
    Qu, Conghui
    Jeon, Jihyoun
    Edlund, Christopher K.
    Greenside, Peyton
    Wainberg, Michael
    Schumacher, Fredrick R.
    Smith, Joshua D.
    Levine, David M.
    Nelson, Sarah C.
    Sinnott-Armstrong, Nasa A.
    Albanes, Demetrius
    Alonso, M. Henar
    Anderson, Kristin
    Arnau-Collell, Coral
    Arndt, Volker
    Bamia, Christina
    Banbury, Barbara L.
    Baron, John A.
    Berndt, Sonja I.
    Bezieau, Stephane
    Bishop, D. Timothy
    Boehm, Juergen
    Boeing, Heiner
    Brenner, Hermann
    Brezina, Stefanie
    Buch, Stephan
    Buchanan, Daniel D.
    Burnett-Hartman, Andrea
    Butterbach, Katja
    Caan, Bette J.
    Campbell, Peter T.
    Carlson, Christopher S.
    Castellvi-Bel, Sergi
    Chan, Andrew T.
    Chang-Claude, Jenny
    Chanock, Stephen J.
    Chirlaque, Maria-Dolores
    Cho, Sang Hee
    Connolly, Charles M.
    Cross, Amanda J.
    Cuk, Katarina
    Curtis, Keith R.
    de la Chapelle, Albert
    Doheny, Kimberly F.
    Duggan, David
    Easton, Douglas F.
    Elias, Sjoerd G.
    Elliott, Faye
    English, Dallas R.
    Feskens, Edith J. M.
    Figueiredo, Jane C.
    Fischer, Rocky
    FitzGerald, Liesel M.
    Forman, David
    Gala, Manish
    Gallinger, Steven
    Gauderman, W. James
    Giles, Graham G.
    Gillanders, Elizabeth
    Gong, Jian
    Goodman, Phyllis J.
    Grady, William M.
    Grove, John S.
    Gsur, Andrea
    Gunter, Marc J.
    Haile, Robert W.
    Hampe, Jochen
    Hampel, Heather
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hayes, Richard B.
    Hofer, Philipp
    Hoffmeister, Michael
    Hopper, John L.
    Hsu, Wan-Ling
    Huang, Wen-Yi
    Hudson, Thomas J.
    Hunter, David J.
    Ibanez-Sanz, Gemma
    Idos, Gregory E.
    Ingersoll, Roxann
    Jackson, Rebecca D.
    Jacobs, Eric J.
    Jenkins, Mark A.
    Joshi, Amit D.
    Joshu, Corinne E.
    Keku, Temitope O.
    Key, Timothy J.
    Kim, Hyeong Rok
    Kobayashi, Emiko
    Kolonel, Laurence N.
    Kooperberg, Charles
    Kuehn, Tilman
    Kury, Sebastien
    Kweon, Sun-Seog
    Larsson, Susanna C.
    Laurie, Cecelia A.
    Le Marchand, Loic
    Leal, Suzanne M.
    Lee, Soo Chin
    Lejbkowicz, Flavio
    Lemire, Mathieu
    Li, Christopher I.
    Li, Li
    Lieb, Wolfgang
    Lin, Yi
    Lindblom, Annika
    Lindor, Noralane M.
    Ling, Hua
    Louie, Tin L.
    Mannisto, Satu
    Markowitz, Sanford D.
    Martin, Vicente
    Masala, Giovanna
    McNeil, Caroline E.
    Melas, Marilena
    Milne, Roger L.
    Moreno, Lorena
    Murphy, Neil
    Myte, Robin
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Naccarati, Alessio
    Newcomb, Polly A.
    Offit, Kenneth
    Ogino, Shuji
    Onland-Moret, N. Charlotte
    Pardini, Barbara
    Parfrey, Patrick S.
    Pearlman, Rachel
    Perduca, Vittorio
    Pharoah, Paul D. P.
    Pinchev, Mila
    Platz, Elizabeth A.
    Prentice, Ross L.
    Pugh, Elizabeth
    Raskin, Leon
    Rennert, Gad
    Rennert, Hedy S.
    Riboli, Elio
    Rodriguez-Barranco, Miguel
    Romm, Jane
    Sakoda, Lori C.
    Schafmayer, Clemens
    Schoen, Robert E.
    Seminara, Daniela
    Shah, Mitul
    Shelford, Tameka
    Shin, Min-Ho
    Shulman, Katerina
    Sieri, Sabina
    Slattery, Martha L.
    Southey, Melissa C.
    Stadler, Zsofia K.
    Stegmaier, Christa
    Su, Yu-Ru
    Tangen, Catherine M.
    Thibodeau, Stephen N.
    Thomas, Duncan C.
    Thomas, Sushma S.
    Toland, Amanda E.
    Trichopoulou, Antonia
    Ulrich, Cornelia M.
    Van den Berg, David J.
    van Duijnhoven, Franzel J. B.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    van Kranen, Henk
    Vijai, Joseph
    Visvanathan, Kala
    Vodicka, Pavel
    Vodickova, Ludmila
    Vymetalkova, Veronika
    Weigl, Korbinian
    Weinstein, Stephanie J.
    White, Emily
    Win, Aung Ko
    Wolf, C. Roland
    Wolk, Alicja
    Woods, Michael O.
    Wu, Anna H.
    Zaidi, Syed H.
    Zanke, Brent W.
    Zhang, Qing
    Zheng, Wei
    Scacheri, Peter C.
    Potter, John D.
    Bassik, Michael C.
    Kundaje, Anshul
    Casey, Graham
    Moreno, Victor
    Abecasis, Goncalo R.
    Nickerson, Deborah A.
    Gruber, Stephen B.
    Hsu, Li
    Peters, Ulrike
    Discovery of common and rare genetic risk variants for colorectal cancer2019In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 1, p. 76-+Article in journal (Refereed)
    Abstract [en]

    To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.

  • 31.
    Isaksson-Mettävainio, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dahlin, Anna M
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Rutegård, Jörgen
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Henriksson, Maria L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    High SMAD4 levels appear in MSI and hypermethylated colon cancers, and indicate a better prognosis2012In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 131, p. 779-788Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer (CRC) is one of the most common causes of cancer related deaths in western countries. CRC are commonly divided in cancers showing microsatellite stability (MSS) or microsatellite instability (MSI). A more novel classification is dependent on promoter hypermethylation of CpG islands (the CpG island methylator phenotype, CIMP), where cancers show high, low or negative methylation status. SMAD4, located on chromosome 18q, has been thoroughly investigated during the last years. Loss of SMAD4 expression has been reported to correlate with poor CRC patient prognosis. In this study we analyze the impact of SMAD4 expression on prognosis in relation to MSI screening status and CIMP status. 479 paraffin-embedded specimens of CRC were examined for nuclear SMAD4 expression using immunohistochemistry. The tumors were scored loss (-), moderate (+) and high (++) expressing tumors. Loss of SMAD4 correlated significantly with decreased survival in all colon cancer patients. High SMAD4 expression, on the other hand, was significantly associated with increased survival, especially in colon cancer patients which has undergone potential curative surgery. In addition, in MSI tumors and CIMP-high tumors, high SMAD4 expression was significantly related to increase in survival, while loss of SMAD4 resulted in a significantly poorer prognosis. SMAD4 expression was not correlated to prognosis in rectal cancer cases. We conclude, loss of SMAD4 indicates a poor prognosis in colon cancer patients. The novel findings that high SMAD4 expression predicts a better prognosis suggests that SMAD4 immunohistochemistry could constitute a prognostic marker in combination with CIMP and MSI screening status.

  • 32.
    Isaksson-Mettävainio, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Öberg, Åke
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Stenling, Roger
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Henriksson, Maria L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    c-Met expression in primary tumors and their corresponding distant metastases2009In: Molecular Medicine Reports, ISSN 1791-2997, Vol. 1, no 6, p. 787-790Article in journal (Refereed)
    Abstract [en]

    c-Met is a receptor tyrosine kinase that has beenimplicated in the pathogenesis and growth of a wide variety ofhuman malignancies, including CRC, but its role in metastasisis largely unknown. We compared c-Met expression in primaryhuman colorectal carcinomas and distant metastases from thesame patients. Formalin-fixed paraffin-embedded tissuesamples from 69 colorectal cancer patients were obtained. Theprotein expression of c-Met was evaluated immunohistochemicallyusing a commercial antibody. The difference inexpression between primary tumors and their correspondingdistant metastases was analyzed using the Wilcoxon signedranktest. c-Met expression was statistically significantlylower in the distant metastases compared to their correspondingprimary tumors (p<0.001), whereas no difference was foundbetween lymph node metastases and their correspondingprimary tumors (p=0.957). The degree of c-Met expressionwas not related to clinicopathological characteristics such astumor grade and Dukes' stage at the time of primary tumordiagnosis, or to the location of the distant metastases. Wedemonstrated that c-Met expression is often reduced in distantmetastases compared to their corresponding primary colorectaltumors. Additional studies of c-Met activation and signaltransduction will increase our knowledge about the role ofc-Met in colorectal cancer metastasis.

  • 33. Jenab, Mazda
    et al.
    Ferrari, Pietro
    Slimani, Nadia
    Norat, Teresa
    Casagrande, Corinne
    Overad, Kim
    Olsen, Anja
    Stripp, Connie
    Tjönneland, Anne
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Kesse, Emmanuelle
    Nieters, Alexandra
    Bergmann, Manuela
    Boeing, Heiner
    Naska, Androniki
    Trichopoulou, Antonia
    Palli, Domenico
    Krogh, Vittorio
    Celentano, Egidio
    Tumino, Rosario
    Sacerdote, Carlotta
    Bueno-de-Mesquita, Hendrik B
    Ocké, Marga C
    Peeters, Petra H M
    Engeset, Dagrun
    Quirós, José R
    Gonzcalez, Carlos A
    Martínez, Carmen
    Chirlaque, Maria D
    Ardanaz, Eva
    Dorronsoro, Miren
    Wallstrröm, Peter
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Bingham, Sheila
    San Joaquin, Miguel A
    Saracci, Rodolfo
    Kaaks, Rudolf
    Riboli, Elio
    Association of nut and seed intake with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition.2004In: Cancer Epidemiology Biomarkers & Prevention, ISSN 1055-9965, Vol. 13, no 10, p. 1595-603Article in journal (Refereed)
  • 34. Jenab, Mazda
    et al.
    Sabate, Joan
    Slimani, Nadia
    Ferrari, Pietro
    Mazuir, Mathieu
    Casagrande, Corinne
    Deharveng, Genevieve
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Boeing, Heiner
    Weikert, Cornelia
    Linseisen, Jakob
    Rohrmann, Sabine
    Trichopoulou, Antonia
    Naska, Androniki
    Palli, Domenico
    Sacerdote, Carlotta
    Tumino, Rosario
    Mattiello, Amalia
    Pala, Valeria
    Bueno-de-Mesquita, H Bas
    Ocke, Marga C
    Peeters, Petra H
    Engeset, Dagrun
    Skeie, Gurie
    Jakszyn, Paula
    Ardanaz, Eva
    Quiros, J Ramon
    Dolores Chirlaque, Maria
    Martinez, Carmen
    Amiano, Pilar
    Berglund, Göran
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bingham, Sheila
    Key, Timothy
    Riboli, Elio
    Consumption and portion sizes of tree nuts, peanuts and seeds in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts from 10 European countries2006In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 96, no S2, p. 12-23Article in journal (Refereed)
    Abstract [en]

    Tree nuts, peanuts and seeds are nutrient dense foods whose intake has been shown to be associated with reduced risk of some chronic diseases. They are regularly consumed in European diets either as whole, in spreads or from hidden sources (e.g. commercial products). However, little is known about their intake profiles or differences in consumption between European countries or geographic regions. The objective of this study was to analyse the population mean intake and average portion sizes in subjects reporting intake of nuts and seeds consumed as whole, derived from hidden sources or from spreads. Data was obtained from standardised 24-hour dietary recalls collected from 36 994 subjects in 10 different countries that are part of the European Prospective Investigation into Cancer and Nutrition (EPIC). Overall, for nuts and seeds consumed as whole, the percentage of subjects reporting intake on the day of the recall was: tree nuts=4 center dot 4%, peanuts=2 center dot 3 % and seeds=1 center dot 3 %. The data show a clear northern (Sweden: mean intake=0 center dot 15 g/d, average portion size=15 center dot 1 g/d) to southern (Spain: mean intake=2 center dot 99 g/d, average portion size=34 center dot 7 g/d) European gradient of whole tree nut intake. The three most popular tree nuts were walnuts, almonds and hazelnuts, respectively. In general, tree nuts were more widely consumed than peanuts or seeds. In subjects reporting intake, men consumed a significantly higher average portion size of tree nuts (28 center dot 5 v. 23 center dot 1 g/d, P < 0 center dot 01) and peanuts (46 center dot 1 v. 35 center dot 1 g/d, P < 0 center dot 01) per day than women. These data may be useful in devising research initiatives and health policy strategies based on the intake of this food group.

  • 35.
    Johansson, Ingegerd
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, M
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Validity of food frequency questionnaire estimated intakes of folate and other B vitamins in a region without folic acid fortification.2010In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 64, no 8, p. 905-913Article in journal (Refereed)
    Abstract [en]

    Background/Objectives: 

    B vitamins have been implicated in major chronic diseases but results have been inconsistent. This study evaluated the accuracy of dietary intakes of folate, vitamin B12, riboflavin and vitamin B6 as measured by the Northern Sweden Food Frequency Questionnaire (FFQ) against repeated 24-h recalls (24HR) and plasma levels, taking into consideration the MTHFR 677C>T polymorphism.

    Subjects/Methods: 

    B vitamin intakes assessed by a semi-quantitative FFQ designed to measure the intake over the previous year were compared with those from 10 24HR, as well as to plasma levels of folate and vitamin B12, in randomly selected men (n=96) and women (n=99) aged 30–60 years. FFQ-based B-vitamin intakes were also compared with plasma levels of B-vitamins and with MTHFR 677C4T genotype in 878 men, aged 40–61 years.

    Results: 

    Intakes of vitamins B12 and riboflavin were similar, whereas folate and B6 intakes were 16–27% higher, as estimated by FFQ versus 24HR. Spearman correlation coefficients between the two methods ranged from 0.31 to 0.63 (all P0.002), and were lowest for vitamin B12. Intakes estimated by FFQ were correlated with plasma levels, but coefficients were lower (range: 0.13–0.33), particularly for vitamin B12 in men (0.15–0.18). Folate intake was not correlated with plasma levels in subjects with the MTHFR 677 T/T genotype.

    Conclusions: 

    The validity of the Northern Sweden FFQ for assessing B vitamin intake is similar to that of many other FFQs used in large-scale studies. The FFQ is suitable for ranking individuals by intake of folate, riboflavin, vitamin B6 and to a lesser extent vitamin B12.

  • 36.
    Johansson, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Wiklund, Fredrik
    Adami, Hans-Olov
    Bälter, Katarina
    Grönberg, Henrik
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    The MTHFR 677C --> T polymorphism and risk of prostate cancer: results from the CAPS study2007In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 18, no 10, p. 1169-1174Article in journal (Refereed)
    Abstract [en]

    The methylenetetrahydrafolate reductase (MTHFR) enzyme may influence cancer development by affecting DNA methylation, synthesis and repair. The MTHFR 677C→T single nucleotide polymorphism (SNP) has been associated with decreased enzyme activity and has therefore been implicated in cancer development. We analyzed the MTHFR 677C→T SNP in 2,777 incident prostate cancer cases and 1,639 population controls from the CAncer Prostate in Sweden study (CAPS). No significant association was found overall between prostate cancer risk and the 677C→T SNP (p = 0.27) with heterozygote (CT) and homozygote (TT) allele carriers showing ORs of 1.12 (95% CI: 0.98–1.27) and 1.02 (95% CI: 0.80–1.30), respectively. In the subgroup of low risk prostate cancer, heterozygote—but not homozygote—allele carriers displayed a slight over-risk with an OR of 1.21 (95% CI: 1.03–1.41). Among men under 65 years of age, the 677C→T SNP was associated with prostate cancer risk (p = 0.007), with odds ratios of 1.33 (95% CI: 1.09–1.63) for heterozygote allele carriers and 0.86 (95% CI: 0.6–1.24) for homozygote allele carriers. However, this association was attributed to a shift in the genotype distribution in the young controls. In conclusion, our results do not provide strong support for the hypothesis that the MTHFR 677C→T polymorphism is related to prostate cancer risk.

  • 37.
    Johansson, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Vollset, Stein Emil
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Key, Tim
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ueland, Per M
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Prospective investigation of one-carbon metabolism in relation to prostate cancer risk: results from the NSHDC studyManuscript (Other academic)
  • 38.
    Johansson, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Vollset, Stein Emil
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Key, Tim
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Midttun, Øivind
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Ueland, Per M
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites2009In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 18, no 5, p. 1538-1543Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1538-43).

  • 39. Leenders, Max
    et al.
    Siersema, Peter D
    Overvad, Kim
    Tjønneland, Anne
    Olsen, Anja
    Boutron-Ruault, Marie-Christine
    Bastide, Nadia
    Fagherazzi, Guy
    Katzke, Verena
    Kühn, Tilman
    Boeing, Heiner
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Lagiou, Pagona
    Klinaki, Eleni
    Masala, Giovanna
    Grioni, Sara
    Santucci De Magistris, Maria
    Tumino, Rosario
    Ricceri, Fulvio
    Peeters, Petra H M
    Lund, Eiliv
    Skeie, Guri
    Weiderpass, Elisabete
    Quirós, J Ramón
    Agudo, Antonio
    Sánchez, María-José
    Dorronsoro, Miren
    Navarro, Carmen
    Ardanaz, Eva
    Ohlsson, Bodil
    Jirström, Karin
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J
    Romieu, Isabelle
    Huybrechts, Inge
    Cross, Amanda J
    Murphy, Neil
    Riboli, Elio
    Bueno-de-Mesquita, H Bas
    Subtypes of fruit and vegetables, variety in consumption and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 11, p. 2705-2714Article in journal (Refereed)
    Abstract [en]

    Previously, a lower risk of colorectal cancer was observed with fruit and vegetable consumption in the European Prospective Investigation into Cancer and Nutrition within a follow-up period of 9 years which was not fully supported by a recent meta-analysis. Therefore, we were interested in the relation with extended follow-up, also focusing on single subtypes and a variety of intake of fruit and vegetables. Fruit and vegetable consumption was assessed at baseline. After an average of 13 years of follow-up, 3,370 participants were diagnosed with colon or rectal cancer. Diet diversity scores were constructed to quantify variety in fruit and vegetable consumption. A lower risk of colon cancer was observed with higher self-reported consumption of fruit and vegetable combined (HR Q4 vs. Q1 0.87, 95% CI 0.75-1.01, p for trend 0.02), but no consistent association was observed for separate consumption of fruits and vegetables. No associations with risk of rectal cancer were observed. The few observed associations for some fruit and vegetable subtypes with colon cancer risk may have been due to chance. Variety in consumption of fruits and vegetables was not associated with a lower risk of colon or rectal cancer. Although a lower risk of colon cancer is suggested with high consumption of fruit and vegetables, this study does not support a clear inverse association between fruit and vegetable consumption and colon or rectal cancer beyond a follow-up of more than 10 years. Attenuation of the risk estimates from dietary changes over time cannot be excluded, but appears unlikely.

  • 40. Leufkens, Anke M
    et al.
    Van Duijnhoven, Fränzel J B
    Siersema, Peter D
    Boshuizen, Hendriek C
    Vrieling, Alina
    Agudo, Antonio
    Gram, Inger T
    Weiderpass, Elisabete
    Dahm, Christina
    Overvad, Kim
    Tjønneland, Anne
    Olsen, Anja
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Morois, Sophie
    Palli, Domenico
    Grioni, Sara
    Tumino, Rosario
    Sacerdote, Charlotta
    Mattiello, Amalia
    Herman, Silke
    Kaaks, Rudolf
    Steffen, Annika
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Peeters, Petra H
    van Gils, Carla H
    van Kranen, Henk
    Lund, Eliv
    Dumeaux, Vanessa
    Engeset, Dagrun
    Rodríguez, Laudina
    Sánchez, Maria-José
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Manjer, Jonas
    Almquist, Martin
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Khaw, Kay-Tee
    Wareham, Nick
    Tsilidis, Konstantinos K
    Straif, Kurt
    Leon-Roux, Maria
    Vineis, Paul
    Norat, Teresa
    Riboli, Elio
    Bueno-de-Mesquita, H Bas
    Cigarette smoking and colorectal cancer risk in the European prospective investigation into cancer and nutrition study2011In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 9, no 2, p. 137-144Article in journal (Refereed)
    Abstract [en]

    Ever smokers have an increased risk of colon cancer, which appeared to be more pronounced in the proximal than the distal colon location.

  • 41. Linseisen, Jakob
    et al.
    Rohrmann, Sabine
    Norat, Teresa
    Gonzalez, Carlos A
    Dorronsoro Iraeta, Miren
    Morote Gomes, Patrocinio
    Chirlaque, Maria-Dolores
    Pozo, Basilio G
    Ardanaz, Eva
    Mattisson, Irene
    Pettersson, Ulrika
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Bingham, Sheila A
    McTaggart, Alison
    Spencer, Elizabeth A
    Overvad, Kim
    Tjönneland, Anne
    Stripp, Connie
    Clavel-Chapelon, Francoíse
    Kesse, Emmanuelle
    Boeing, Heiner
    Klipstein-Grobusch, Kerstin
    Trichopoulou, Antonia
    Vasilopoulou, Effie
    Bellos, George
    Pala, Valeria
    Masala, Giovanna
    Tumino, Rosario
    Sacerdote, Carlotta
    Del Pezzo, Mariarosaria
    Bueno-de-Mesquita, H Bas
    Ocke, Marga C
    Peeters, Petra H M
    Engeset, Dagrun
    Skeie, Guri
    Slimani, Nadia
    Riboli, Elio
    Dietary intake of different types and characteristics of processed meat which might be associated with cancer risk--results from the 24-hour diet recalls in the European Prospective Investigation into Cancer and Nutrition (EPIC).2006In: Public Health Nutr, ISSN 1368-9800, Vol. 9, no 4, p. 449-64Article in journal (Refereed)
  • 42. Mullee, Amy
    et al.
    Romaguera, Dora
    Pearson-Stuttard, Jonathan
    Viallon, Vivian
    Stepien, Magdalena
    Freisling, Heinz
    Fagherazzi, Guy
    Mancini, Francesca Romana
    Boutron-Ruault, Marie-Christine
    Kühn, Tilman
    Kaaks, Rudolf
    Boeing, Heiner
    Aleksandrova, Krasimira
    Tjønneland, Anne
    Halkjær, Jytte
    Overvad, Kim
    Weiderpass, Elisabete
    Skeie, Guri
    Parr, Christine L.
    Quirós, J Ramón
    Agudo, Antonio
    Sánchez, Maria-Jose
    Amiano, Pilar
    Cirera, Lluís
    Ardanaz, Eva
    Khaw, Kay-Tee
    Tong, Tammy Y. N.
    Schmidt, Julie A.
    Trichopoulou, Antonia
    Martimianaki, Georgia
    Karakatsani, Anna
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Bueno-de-Mesquita, Bas
    Verschuren, W. M. Monique
    Boer, Jolanda M. A.
    Vermeulen, Roel
    Ramne, Stina
    Sonestedt, Emily
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lif Holgerson, Pernilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tsilidis, Konstantinos K.
    Heath, Alicia K.
    Muller, David
    Riboli, Elio
    Gunter, Marc J.
    Murphy, Neil
    Association Between Soft Drink Consumption and Mortality in 10 European Countries2019In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114Article in journal (Refereed)
    Abstract [en]

    Importance: Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date.

    Objective: To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality.

    Design, Setting, and Participants: This population-based cohort study involved participants (n = 451 743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018.

    Exposure: Consumption of total, sugar-sweetened, and artificially sweetened soft drinks.

    Main Outcomes and Measures: Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors.

    Results: In total, 521 330 individuals were enrolled. Of this total, 451 743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321 081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41 693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of <1 glass per month) of total soft drinks (hazard ratio [HR], 1.17; 95% CI, 1.11-1.22; P < .001), sugar-sweetened soft drinks (HR, 1.08; 95% CI, 1.01-1.16; P = .004), and artificially sweetened soft drinks (HR, 1.26; 95% CI, 1.16-1.35; P < .001). Positive associations were also observed between artificially sweetened soft drinks and deaths from circulatory diseases (≥2 glasses per day vs <1 glass per month; HR, 1.52; 95% CI, 1.30-1.78; P < .001) and between sugar-sweetened soft drinks and deaths from digestive diseases (≥1 glass per day vs <1 glass per month; HR, 1.59; 95% CI, 1.24-2.05; P < .001).

    Conclusions and Relevance: This study found that consumption of total, sugar-sweetened, and artificially sweetened soft drinks was positively associated with all-cause deaths in this large European cohort; the results are supportive of public health campaigns aimed at limiting the consumption of soft drinks.

  • 43.
    Myte, Robin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gylling, Björn
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Häggström, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden..
    Zingmark, Carl
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Löfgren Burström, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status2019In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, no 2, p. 327-337Article in journal (Refereed)
    Abstract [en]

    Factors related to energy metabolism and the metabolic syndrome, such as higher body mass index (BMI), blood glucose, or blood lipids, and blood pressure, are associated with an increased risk of colorectal cancer (CRC). However, CRC is a heterogeneous disease, developing through distinct pathways with differences in molecular characteristics and prognosis, and possibly also in risk factors. For subtypes defined by KRAS and BRAF mutation status, BMI is the only metabolic factor previously studied, with inconsistent findings. We investigated whether associations between BMI, blood glucose, blood lipids, and blood pressure and CRC risk differed by tumor KRAS and BRAF mutation status in 117,687 participants from two population-based cohorts within the Northern Sweden Health and Disease Study (NSHDS). Hazard ratios (HRs) for overall CRC and CRC subtypes by metabolic factors were estimated with Cox proportional hazards regression, using multiple imputation to handle missing exposure and tumor data. During a median follow-up of 15.6 years, we acquired 1,250 prospective CRC cases, of which 766 cases had complete baseline and molecular tumor data. Consistent with previous evidence, higher BMI, total cholesterol, triglyceride levels, and blood pressure were associated with an increased risk of overall CRC (HRs per 1 standard deviation increase: 1.07 to 1.12). These associations were similar regardless of CRC subtype by KRAS and BRAF mutation status (all pheterogeneity > 0.05). The same was true for subtypes based on microsatellite instability status. Poor metabolic health may therefore be a universal mechanism for colorectal cancer, acting across multiple developmental pathways.

  • 44.
    Myte, Robin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gylling, Björn
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Häggström, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Löfgren-Burström, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Huyghe, Jeroen R.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Meyer, Klaus
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ueland, Per Magne
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    One-carbon metabolism biomarkers and genetic variants in relation to colorectal cancer risk by KRAS and BRAF mutation status2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0196233Article in journal (Refereed)
    Abstract [en]

    Disturbances in one-carbon metabolism, intracellular reactions involved in nucleotide synthesis and methylation, likely increase the risk of colorectal cancer (CRC). However, results have been inconsistent. To explore whether this inconsistency could be explained by intertumoral heterogeneity, we evaluated a comprehensive panel of one-carbon metabolism biomarkers and some single nucleotide polymorphisms (SNPs) in relation to the risk of molecular subtypes of CRC defined by mutations in the KRAS and BRAF oncogenes. This nested case-control study included 488 CRC cases and 947 matched controls from two population-based cohorts in the Northern Sweden Health and Disease Study. We analyzed 14 biomarkers and 17 SNPs in prediagnostic blood and determined KRAS and BRAF mutation status in tumor tissue. In a multivariate network analysis, no variable displayed a strong association with the risk of specific CRC subtypes. A non-synonymous SNP in the CTH gene, rs1021737, had a stronger association compared with other variables. In subsequent univariate analyses, participants with variant rs1021737 genotype had a decreased risk of KRAS-mutated CRC (OR per allele = 0.72, 95% CI = 0.50, 1.05), and an increased risk of BRAF-mutated CRC (OR per allele = 1.56, 95% CI = 1.07, 2.30), with weak evidence for heterogeneity (Pheterogeneity = 0.01). This subtype-specific SNP association was not replicated in a case-case analysis of 533 CRC cases from The Cancer Genome Atlas (P = 0.85). In conclusion, we found no support for clear subtype-specific roles of one-carbon metabolism biomarkers and SNPs in CRC development, making differences in CRC molecular subtype distributions an unlikely explanation for the varying results on the role of one-carbon metabolism in CRC development across previous studies. Further investigation of the CTH gene in colorectal carcinogenesis with regards to KRAS and BRAF mutations or other molecular characteristics of the tumor may be warranted.

  • 45.
    Myte, Robin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gylling, Björn
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Häggström, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Ueland, Per Magne
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Untangling the role of one-carbon metabolism in colorectal cancer risk: a comprehensive Bayesian network analysis2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 43434Article in journal (Refereed)
    Abstract [en]

    The role of one-carbon metabolism (1CM), particularly folate, in colorectal cancer (CRC) development has been extensively studied, but with inconclusive results. Given the complexity of 1CM, the conventional approach, investigating components individually, may be insufficient. We used a machine learning-based Bayesian network approach to study, simultaneously, 14 circulating one-carbon metabolites, 17 related single nucleotide polymorphisms (SNPs), and several environmental factors in relation to CRC risk in 613 cases and 1190 controls from the prospective Northern Sweden Health and Disease Study. The estimated networks corresponded largely to known biochemical relationships. Plasma concentrations of folate (direct), vitamin B6 (pyridoxal 5-phosphate) (inverse), and vitamin B2 (riboflavin) (inverse) had the strongest independent associations with CRC risk. Our study demonstrates the importance of incorporating B-vitamins in future studies of 1CM and CRC development, and the usefulness of Bayesian network learning for investigating complex biological systems in relation to disease.

  • 46.
    Myte, Robin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gylling, Björn
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Schneede, Jörn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
    Ueland, Per Magne
    Häggström, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Components of One-carbon Metabolism Other than Folate and Colorectal Cancer Risk2016In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 27, no 6, p. 787-796Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Despite extensive study, the role of folate in colorectal cancer remains unclear. Research has therefore begun to address the role of other elements of the folate-methionine metabolic cycles. This study investigated factors other than folate involved in one-carbon metabolism, i.e., choline, betaine, dimethylglycine, sarcosine, and methionine and relevant polymorphisms, in relation to the risk of colorectal cancer in a population with low intakes and circulating levels of folate.

    METHODS: This was a prospective case-control study of 613 case subjects and 1,190 matched control subjects nested within the population-based Northern Sweden Health and Disease Study. We estimated odds ratios (OR) by conditional logistic regression, and marginal risk differences with weighted maximum likelihood estimation using incidence data from the study cohort.

    RESULTS: Higher plasma concentrations of methionine and betaine were associated with modest colorectal cancer risk reductions (OR [95% confidence interval {CI}] for highest versus lowest tertile: 0.76 [0.57, 0.99] and 0.72 [0.55, 0.94], respectively). Estimated marginal risk differences corresponded to approximately 200 fewer colorectal cancer cases per 100,000 individuals on average. We observed no clear associations between choline, dimethylglycine, or sarcosine and colorectal cancer risk. The inverse association of methionine was modified by plasma folate concentrations (OR [95% CI] for highest/lowest versus lowest/lowest tertile of plasma methionine/folate concentrations 0.39 [0.24, 0.64], Pinteraction = 0.06).

    CONCLUSIONS: In this population-based, nested case-control study with a long follow-up time from baseline to diagnosis (median: 8.2 years), higher plasma concentrations of methionine and betaine were associated with lower colorectal cancer risk. See Video Abstract at http://links.lww.com/EDE/B83.

  • 47.
    Myte, Robin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University.
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sundkvist, Anneli
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Gylling, Björn
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Häggström, Jenny
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Zingmark, Carl
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Löfgren Burström, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Metabolic biomarkers and the risk of molecular subtypes of colorectal cancerManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Body fatness measured as high body mass index (BMI) increase the risk for colorectal cancer (CRC). The mechanisms behind the relationship are not fully understood, but might include insulin resistance and changes in adipokine concentrations produced by adipose tissue. Yet, associations between circulating biomarkers related to these mechanisms and CRC risk have been somewhat inconsistent, possibly due to CRC heterogeneity. To better understand the role of insulin resistance and adipokines in CRC development, we therefore investigated circulating biomarkers related to these mechanisms in relation to molecular subtypes of CRC.

    Methods: This was a prospective case-control study of 1010 cases and 1:1 matched controls nested within the population-based Northern Sweden Health and Disease Study (NSHDS). Concentrations of insulin, C-peptide, adiponectin, and leptin were quantified in prediagnostic plasma using immunoassays and related to CRC and CRC subtypes defined by mutations in BRAF and KRAS, and microsatellite instability (MSI) status analyzed in tumor tissue. Odds ratios (ORs) and 95% confidence intervals (CIs) for CRC by metabolic biomarker levels were calculated with conditional logistic regression.

    Results: Higher C-peptide and lower adiponectin were associated with an increased CRC risk (ORs per 1 standard deviation increase (95% CI): 1.11 (1.01, 1.23) and 0.91 (0.83, 1.00), respectively). The associations were attenuated when adjusting for BMI (ORs (95% CI): 1.07 (0.96, 1.19) and 0.93 (0.84, 1.03), respectively), with the potential exception of the association of C-peptide in women. Circulating insulin and leptin were not associated with CRC risk. We found no clear differences in the association between any biomarkers and CRC risk by molecular subtypes defined by KRAS and BRAF mutation status (Pheterogeneity>0.6), or MSI status (Pheterogeneity>0.3).

    Conclusion: Circulating biomarkers of insulin resistance and adipokines were not associated with CRC or specific molecular subtypes of CRC defined by KRAS and BRAF mutation or MSI status.

  • 48.
    Myte, Robin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sundkvist, Anneli
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Harlid, Sophia
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Circulating levels of inflammatory markers and DNA methylation, an analysis of repeated samples from a population based cohort2019In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 14, no 7, p. 649-659Article in journal (Refereed)
    Abstract [en]

    DNA methylation in blood may adapt to conditions affecting our health, such as inflammation, and multiple studies have identified differential DNA methylation related to smoking, obesity and various diseases. The purpose of this study was to evaluate previously reported, and explore possible new, associations between levels of inflammatory markers and DNA methylation in blood. We used a well-characterized study population consisting of 127 individuals, all of whom were participants in the population-based Vasterbotten Intervention Programme cohort and had provided two blood samples, ten years apart. Levels of CRP and 160 other proteins were measured in plasma, and DNA methylation levels (assessed using the 850K Illumina Infinium MethylationEPIC BeadChip) were measured in white blood cell DNA. Associations between CpG methylation and protein levels were estimated using linear mixed models. In the study we were able to confirm the direction for 85 of 102 previously reported protein-methylation associations. Depicting associations in a network allowed us to identify CpG sites with associations to multiple proteins, and ten CpG sites were each associated with three or more inflammatory markers. Furthermore, two genetic regions included nine additional unreported CpG sites that may represent trans-acting methylation sites. Our study supports a complex interaction between DNA methylation and circulating proteins involved in the inflammatory response. The notion of trans-acting methylation sites affecting, or being affected by, the expression of genes on completely different chromosomes should be taken into account when interpreting results from epigenome-wide association studies.

  • 49.
    Nilsson, Lena Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Dahlgren, Lars
    Umeå University, Faculty of Social Sciences, Department of Sociology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Brustad, Magritt
    Sjölander, Per
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Diet and lifestyle of the Sami of southern Lapland in the 1930s - 1950s and today2011In: International Journal of Circumpolar Health, ISSN 1239-9736, E-ISSN 2242-3982, Vol. 70, no 3, p. 301-318Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To describe the lifestyle of the Sami of southern Lapland 50 to 70 years ago in relation to the present-day Sami and non-Sami populations and, thereby, to provide a basis for future studies of culturally related determinants of health and illness.

    STUDY DESIGN: A qualitative analysis, and a quantitative comparison of Sami and non-Sami groups.

    METHODS: Semi-structured interviews were conducted with 20 elderly Sami concerning their parents' lifestyle and diet 50 to 70 years ago. Questionnaire data from 81 reindeer-herding Sami, 226 non-reindeer-herding Sami and 1,842 sex-, age- and geographically matched non-Sami from the population-based Västerbotten Intervention Project were analysed by non-parametric tests and partial least squares methodology.

    RESULTS: Surprisingly, fatty fish may have been more important than reindeer meat for the Sami of southern Lapland in the 1930s to 1950s, and it is still consumed more frequently by reindeer-herding Sami than nonreindeer-herding Sami and non-Sami. Other dietary characteristics of the historical Sami and present-day reindeer-herding Sami were higher intakes of fat, blood and boiled coffee, and lower intakes of bread, fibre and cultivated vegetables, compared with present-day non-Sami. Physical activity was also a part of the daily life of the Sami to a greater extent in the 1930s to 1950s than today. Sami men often worked far from home, while the women were responsible for fishing, farming, gardening (which was introduced in the 1930-1950 period), as well as housework and childcare.

    CONCLUSIONS: For studies investigating characteristic lifestyle elements of specific ethnic groups, the elements of greatest acknowledged cultural importance today (in this case reindeer meat) may not be of the most objective importance traditionally.

  • 50.
    Nilsson, Lena Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Consumption of filtered and boiled coffee and the risk of incident cancer: a prospective cohort study2010In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 21, no 10, p. 1533-1544Article in journal (Refereed)
    Abstract [en]

    Background  Despite potentially relevant chemical differences between filtered and boiled coffee, this study is the first to investigate consumption in relation to the risk of incident cancer.

    Methods  Subjects were from the Västerbotten Intervention Project (64,603 participants, including 3,034 cases), with up to 15 years of follow-up. Hazard ratios (HR) were calculated by multivariate Cox regression.

    Results  No associations were found for all cancer sites combined, or for prostate or colorectal cancer. For breast cancer, boiled coffee ≥4 versus <1 occasions/day was associated with a reduced risk (HR = 0.52, CI = 0.30–0.88, p trend = 0.247). An increased risk of premenopausal and a reduced risk of postmenopausal breast cancer were found for both total (HRpremenopausal = 1.69, CI = 0.96–2.98, p trend = 0.015, HRpostmenopausal = 0.60, CI = 0.39–0.93, p trend = 0.006) and filtered coffee (HRpremenopausal = 1.76, CI = 1.04–3.00, p trend = 0.045, HRpostmenopausal = 0.52, CI = 0.30–0.88, p trend = 0.045). Boiled coffee was positively associated with the risk of respiratory tract cancer (HR = 1.81, CI = 1.06–3.08, p trend = 0.084), a finding limited to men. Main results for less common cancer types included total coffee in renal cell cancer (HR = 0.30, CI = 0.11–0.79, p trend = 0.009) and boiled coffee in pancreas cancer (HR = 2.51 CI = 1.15–5.50, p trend = 0.006).

    Conclusion  These findings demonstrate, for the first time, the potential relevance of brewing method in investigations of coffee consumption and cancer risk, but they must be confirmed in future studies.

12 1 - 50 of 84
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf