title: Polymorphisms in ATP-binding cassette transporter genes and interaction with diet and life style factors in relation to colorectal cancer in a Danish prospective case-cohort study.
abstract: OBJECTIVE
  The ATP-binding cassette (ABC) transporter family transports various molecules across the enterocytes in the gut protecting the intestine against potentially harmful substances. Moreover, ABC transporters are involved in mucosal immune defence through interaction with cytokines. The study aimed to assess whether polymorphisms in ABCB1, ABCC2 and ABCG2 were associated with risk of colorectal cancer (CRC) and to investigate gene-environment (dietary factors, smoking and use of non-steroidal anti-inflammatory drugs) and gene-gene interactions between previously studied polymorphisms in IL1B and IL10 and ABC transporter genes in relation to CRC risk.
  
  
  METHODS
  We used a Danish prospective case-cohort study of 1010 CRC cases and 1829 randomly selected participants from the Danish Diet, Cancer and Health cohort. Incidence rate ratios were calculated based on Cox' proportional hazards model.
  
  
  RESULTS
  None of the polymorphisms were associated with CRC, but ABCB1 and ABCG2 haplotypes were associated with risk of CRC. ABCB1/rs1045642 interacted with intake of cereals and fiber (p-Value for interaction (P(int)) = 0.001 and 0.01, respectively). In a three-way analysis, both ABCB1/rs1045642 and ABCG2/rs2231137 in combination with IL10/rs3024505 interacted with fiber intake in relation to risk of CRC (P(int) = 0.0007 and 0.009).
  
  
  CONCLUSIONS
  Our results suggest that the ABC transporters P-glycoprotein/multidrug resistance 1 and BRCP, in cooperation with IL-10, are involved in the biological mechanism underlying the protective effect of fiber intake in relation to CRC. These results should be replicated in other cohorts to rule out chance findings.
authors.affiliation: National Food Institute, Technical University of Denmark , Søborg , Denmark.
authors.forename: Tine Iskov
authors.initials: TI
authors.lastname: Kopp
authors.forename: Vibeke
authors.initials: V
authors.lastname: Andersen
authors.forename: Anne
authors.initials: A
authors.lastname: Tjonneland
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D003718:Denmark / Q000453:epidemiology; D004043:Dietary Fiber / Q000008:administration & dosage; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008019:Life Style; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004043:Dietary Fiber; D016753:Interleukin-10; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C508609:IL10 protein, human
keywords: ATP-binding cassette transporter; colorectal cancer; cytokines; diet; genetic epidemiology; gene–environment interaction; inflammation; non-steroidal anti-inflammatory drug; polymorphism