title: An exon variant in insulin receptor gene is associated with susceptibility to colorectal cancer in women.
abstract: Given the role of insulin resistance in colorectal cancer (CRC), we explored whether genetic variants in insulin (INS), insulin receptor (INSR), insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), insulin-like growth factor 1 (IGF1), and insulin-like growth factor binding protein 3 (IGFBP3) genes were associated with CRC risk. A total of 600 subjects, including 261 cases with CRC and 339 controls, were enrolled in this case-control study. Six polymorphisms in INS (rs689), INSR (rs1799817), IRS1 (rs1801278), IRS2 (rs1805097), IGF1 (rs5742612), and IGFBP3 (rs2854744) genes were genotyped using PCR-RFLP method. No significant difference was observed for INS, INSR, IRS1, IRS2, IGF1, and IGFBP3 genes between the cases and controls. However, the INSR rs1799817 "TT + CT" genotype and "CT" genotype compared with "CC" genotype occurred more frequently in the women with CRC than women controls (P = 0.007; OR = 1.93, 95 %CI = 1.20-3.11 and P = 0.002, OR = 2.15, 95 %CI = 1.31-3.53, respectively), and the difference remained significant after adjustment for confounding factors including age, BMI, smoking status, NSAID use, and family history of CRC (P = 0.018; OR = 1.86, 95 %CI = 1.11-3.10 and P = 0.004, OR = 2.18, 95 %CI = 1.28-3.71, respectively). In conclusion, to our knowledge, this study indicated for the first time that the INSR rs1799817 TT + CT genotype and CT genotype compared with the CC genotype had 1.86-fold and 2.18-fold increased risks for CRC among women, respectively. Furthermore, this finding is in line with previous studies which found significant associations between other variants of the INSR gene and CRC risk. Nevertheless, further studies are required to confirm our findings.
authors.affiliation: Department of Cancer, Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Velenjak, Shahid Chamran Highway, Tehran, 1985711151, Iran, mahmouditouraj@gmail.com.
authors.forename: Touraj
authors.initials: T
authors.lastname: Mahmoudi
authors.forename: Keivan
authors.initials: K
authors.lastname: Majidzadeh-A
authors.forename: Khatoon
authors.initials: K
authors.lastname: Karimi
authors.forename: Negar
authors.initials: N
authors.lastname: Karimi
authors.forename: Hamid
authors.initials: H
authors.lastname: Farahani
authors.forename: Reza
authors.initials: R
authors.lastname: Dabiri
authors.forename: Hossein
authors.initials: H
authors.lastname: Nobakht
authors.forename: Hesamodin
authors.initials: H
authors.lastname: Dolatmoradi
authors.forename: Maral
authors.initials: M
authors.lastname: Arkani
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Zali
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000235:genetics; 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; D008875:Middle Aged; D011972:Receptor, Insulin / Q000235:genetics*
chemical_list: C515497:IGFBP3 protein, human; C526292:IRS1 protein, human; C526297:IRS2 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin