title: Is there an association between variants in candidate insulin pathway genes IGF-I, IGFBP-3, INSR, and IRS2 and risk of colorectal cancer in the Iranian population?
abstract: BACKGROUND
  Several epidemiological studies have shown associations between colorectal cancer (CRC) risk and type 2 diabetes and obesity. Any effects would be expected to be mediated through the insulin pathway. Therefore it is possible that variants of genes encoding components of the insulin pathway play roles in CRC susceptibility. In this study, we hypothesized that polymorphisms in the genes involving the insulin pathway are associated with risk of CRC.
  
  
  METHODS
  The associations of four single nucleotide polymorphisms (SNPs) in IGF-I (rs6214), IGFBP-3 (rs3110697), INSR (rs1052371), and IRS2 (rs2289046) genes with the risk of CRC were evaluated using a case-control design with 167 CRC cases and 277 controls by the PCR-RFLP method.
  
  
  RESULTS
  Overall, we observed no significant difference in genotype and allele frequencies between the cases and controls for the IGF-I, IGFBP-3, INSR, IRS2 gene variants and CRC before or after adjusting for confounders (age, BMI, sex, and smoking status). However, we observed that the IRS2 (rs2289046) GG genotype compared with AA+AG genotypes has a protective effect for CRC in normal weight subjects (p=0.035, OR=0.259, 95%CI= 0.074-0.907).
  
  
  CONCLUSIONS
  These findings do not support plausible associations between polymorphic variations in IGF-I, IGFBP-3, INSR, IRS2 genes and risk of CRC. However, the evidence for a link between the IRS2 (rs2289046) variant and risk of CRC dependent on the BMI of the subjects, requires confirmation in subsequent studies with greater sample size.
authors.affiliation: Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran E-mail : mahmouditouraj@gmail.com.
authors.forename: Khatoon
authors.initials: K
authors.lastname: Karimi
authors.forename: Touraj
authors.initials: T
authors.lastname: Mahmoudi
authors.forename: Negar
authors.initials: N
authors.lastname: Karimi
authors.forename: Hesamodin
authors.initials: H
authors.lastname: Dolatmoradi
authors.forename: Maral
authors.initials: M
authors.lastname: Arkani
authors.forename: Hamid
authors.initials: H
authors.lastname: Farahani
authors.forename: Mohsen
authors.initials: M
authors.lastname: Vahedi
authors.forename: Elham
authors.initials: E
authors.lastname: Parsimehr
authors.forename: Reza
authors.initials: R
authors.lastname: Dabiri
authors.forename: Hossein
authors.initials: H
authors.lastname: Nobakht
authors.forename: Asadollah
authors.initials: A
authors.lastname: Asadi
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Zali
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics*; D015992:Body Mass Index; D002277:Carcinoma / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D011972:Receptor, Insulin / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C583557:IGF1 protein, human; C515497:IGFBP3 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; C435941:INSR protein, human; D011972:Receptor, Insulin