Time filter

Source Type

Aabenraa, Denmark

Andersen V.,Organ Center | Andersen V.,University of Southern Denmark | Holst R.,University of Southern Denmark | Kopp T.I.,National Food Institute | And 3 more authors.
PLoS ONE | Year: 2013

Background & Aims:Diet contributes to colorectal cancer development and may be potentially modified. We wanted to identify the biological mechanisms underlying colorectal carcinogenesis by assessment of diet-gene interactions.Methods:The polymorphisms IL10 C-592A (rs1800872), C-rs3024505-T, IL1b C-3737T (rs4848306), G-1464C (rs1143623), T-31C (rs1143627) and PTGS2 (encoding COX-2) A-1195G (rs689466), G-765C (rs20417), and T8473C (rs5275) were assessed in relation to risk of colorectal cancer (CRC) and interaction with diet (red meat, fish, fibre, cereals, fruit and vegetables) and lifestyle (non-steroid-anti-inflammatory drug use and smoking status) was assessed in a nested case-cohort study of nine hundred and seventy CRC cases and 1789 randomly selected participants from a prospective study of 57,053 persons.Results:IL1b C-3737T, G-1464C and PTGS2 T8473C variant genotypes were associated with risk of CRC compared to the homozygous wildtype genotype (IRR=0.81, 95%CI: 0.68-0.97, p=0.02, and IRR=1.22, 95%CI: 1.04-1.44, p=0.02, IRR=0.75, 95%CI: 0.57-0.99, p=0.04, respectively). Interactions were found between diet and IL10 rs3024505 (P-value for interaction (Pint); meat=0.04, fish=0.007, fibre=0.0008, vegetables=0.0005), C-592A (Pint; fibre=0.025), IL1b C-3737T (Pint; vegetables=0.030, NSAID use=0.040) and PTGS2 genotypes G-765C (Pint; meat=0.006, fibre=0.0003, fruit 0.004), and T8473C (Pint; meat 0.049, fruit=0.03) and A-1195G (Pint; meat 0.038, fibre 0.040, fruit=0.059, vegetables=0.025, and current smoking=0.046).Conclusions:Genetically determined low COX-2 and high IL-1β activity were associated with increased risk of CRC in this northern Caucasian cohort. Furthermore, interactions were found between IL10, IL1b, and PTGS2 and diet and lifestyle factors in relation to CRC. The present study demonstrates that gene-environment interactions may identify genes and environmental factors involved in colorectal carcinogenesis. © 2013 Andersen et al. Source

Andersen V.,Organ Center | Andersen V.,University of Southern Denmark | Vogel U.,Helmholtz Center Munich
Genes and Nutrition | Year: 2015

Meat intake is associated with the risk of colorectal cancer. The objective of this systematic review was to evaluate interactions between meat intake and genetic variation in order to identify biological pathways involved in meat carcinogenesis. We performed a literature search of PubMed and Embase using “interaction”, “meat”, “polymorphisms”, and “colorectal cancer”, and data on meat–gene interactions were extracted. The studies were divided according to whether information on meat intake was collected prospectively or retrospectively. In prospective studies, interactions between meat intake and polymorphisms in PTGS2 (encoding COX-2), ABCB1, IL10, NFKB1, MSH3, XPC (Pint = 0.006, 0.01, 0.04, 0.03, 0.002, 0.01, respectively), but not IL1B, HMOX1, ABCC2, ABCG2, NR1I2 (encoding PXR), NR1H2 (encoding LXR), NAT1, NAT2, MSH6, or MLH1 in relation to CRC were found. Interaction between a polymorphism in XPC and meat was found in one prospective and one case–control study; however, the directions of the risk estimates were opposite. Thus, none of the findings were replicated. The results from this systematic review suggest that genetic variation in the inflammatory response and DNA repair pathway is involved in meat-related colorectal carcinogenesis, whereas no support for the involvement of heme and iron from meat or cooking mutagens was found. Further studies assessing interactions between meat intake and genetic variation in relation to CRC in large well-characterised prospective cohorts with relevant meat exposure are warranted. © 2014, The Author(s). Source

Andersen V.,Organ Center | Andersen V.,University of Southern Denmark | Vogel U.,Helmholtz Center Munich
Alimentary Pharmacology and Therapeutics | Year: 2014

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin (acetylsalicylic acid, ASA). Long-term use of NSAIDs has been associated with lowered risk of colorectal cancer (CRC), but the use is hampered by adverse effects. Also, the anti-carcinogenic effects of NSAIDs are incompletely understood. Understanding biological effects of NSAIDs may help developing new preventive medical strategies. Aim To identify gene-environment interactions between genetic variation and NSAID use in relation to risk of CRC. Methods We performed a PubMed literature search and all studies reporting original data on interactions between NSAIDs and polymorphisms in relation to CRC were evaluated. Results We found indications that aspirin interacted with rs6983267 close to MYC (encoding a transcription factor involved in cell cycle progression, apoptosis and cellular transformation) and NSAIDs interacted with rs3024505 and rs1800872 in or close to IL10 (encoding IL-10) in preventing CRC. Homozygous carriers of the variant allele of rs6983267 (ca. 25% of the population) halved their risk for CRC by aspirin use compared to homozygous wildtype carriers who did not benefit from aspirin intake. No interaction between use of NSAIDs and PTGS-2 (encoding COX-2) in relation to CRC risk was detected. Other findings of interactions between genes in inflammatory and oncogenic pathways and NSAIDs were considered suggestive. Conclusions Knowledge of underlying biological effects of NSAIDs in relation to CRC is scarce and the basis for stratifying the patients for preventive treatment is not yet available. Further studies assessing interactions between long-term NSAID exposure and genetic variation in relation to CRC are warranted in large well-characterised prospective cohorts. © 2014 The Authors. Alimentary Pharmacology & Therapeutics Published by John Wiley & Sons Ltd. Source

Kopp T.I.,Technical University of Denmark | Andersen V.,Organ Center | Andersen V.,University of Southern Denmark | Tjonneland A.,Danish Cancer Society | Vogel U.,Helmholtz Center Munich
PLoS ONE | Year: 2015

Maintenance of a balance between commensal bacteria and the mucosal immune system is crucial and intestinal dysbiosis may be a key event in the pathogenesis of colorectal cancer (CRC). The toll-like receptor 4 (TLR4) is an important pattern-recognition receptor that regulates inflammation and barrier function in the gut by a mechanism that involves activation of the nuclear factor-κB (NF-κB) transcription factor. Dietary and life style factors may impact these functions. We therefore used a Danish prospective case-cohort study of 1010 CRC cases and 1829 randomly selected participants from the Danish Diet, Cancer and Health cohort to investigate three polymorphisms in NFKB1 and TLR4 and their possible interactions with diet and life style factors in relation to risk of CRC. Homozygous carriage of the variant allele of the TLR4/rs5030728 polymorphism was associated with increased risk of CRC (incidence rate ratio (IRR) = 1.30; 95% confidence interval (CI): 1.05-1.60; P = 0.02 (gene-dose model); IRR = 1.24; 95%CI: 1.01-1.51; P = 0.04 (recessive model)). Del-carriers of the NFKB1/rs28362491 polymorphism had a 17% (95%CI: 1.03-1.34; P = 0.02) increased risk of CRC compared to homozygous carriers of the ins-allele. However, none of these risk estimates withstood adjustment for multiple comparisons. We found no strong gene-environment interactions between the examined polymorphism and diet and life style factors in relation to CRC risk. © 2015 Kopp et al. Source

Bennike T.,University of Aalborg | Birkelund S.,University of Aalborg | Stensballe A.,University of Aalborg | Andersen V.,University of Southern Denmark | Andersen V.,Organ Center
World Journal of Gastroenterology | Year: 2014

Unambiguous diagnosis of the two main forms of inflammatory bowel diseases (IBD): Ulcerative colitis (UC) and Crohn's disease (CD), represents a challenge in the early stages of the diseases. The diagnosis may be established several years after the debut of symptoms. Hence, protein biomarkers for early and accurate diagnostic could help clinicians improve treatment of the individual patients. Moreover, the biomarkers could aid physicians to predict disease courses and in this way, identify patients in need of intensive treatment. Patients with low risk of disease flares may avoid treatment with medications with the concomitant risk of adverse events. In addition, identification of disease and course specific biomarker profiles can be used to identify biological pathways involved in the disease development and treatment. Knowledge of disease mechanisms in general can lead to improved future development of preventive and treatment strategies. Thus, the clinical use of a panel of biomarkers represents a diagnostic and prognostic tool of potentially great value. The technological development in recent years within proteomic research (determination and quantification of the complete protein content) has made the discovery of novel biomarkers feasible. Several IBD-associated protein biomarkers are known, but none have been successfully implemented in daily use to distinguish CD and UC patients. The intestinal tissue remains an obvious place to search for novel biomarkers, which blood, urine or stool later can be screened for. When considering the protein complexity encountered in intestinal biopsy-samples and the recent development within the field of mass spectrometry driven quantitative proteomics, a more thorough and accurate biomarker discovery endeavor could today be performed than ever before. In this review, we report the current status of the pro-teomics IBD biomarkers and discuss various emerging proteomic strategies for identifying and characterizing novel biomarkers, as well as suggesting future targets for analysis. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved. Source

Discover hidden collaborations