title: Polymorphisms in NFKB1 and TLR4 and interaction with dietary and life style factors in relation to colorectal cancer in a Danish prospective case-cohort study.
abstract: 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.
authors.affiliation: National Food Institute, Technical University of Denmark, 2860 Søborg, Denmark.
authors.forename: Tine Iskov
authors.initials: TI
authors.lastname: Kopp
authors.affiliation: Organ Center, Hospital of Southern Jutland, 6200 Aabenraa, Denmark; Institute of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark; Medical Department, Regional Hospital Viborg, 8800 Viborg, Denmark.
authors.forename: Vibeke
authors.initials: V
authors.lastname: Andersen
authors.affiliation: Danish Cancer Society Research Center, 2100 Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Tjonneland
authors.affiliation: National Research Centre for the Working Environment, 2100 Copenhagen, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003718:Denmark; D004032:Diet; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D051197:Toll-Like Receptor 4