title: Polymorphisms in the insulin-like growth factor axis are associated with gastrointestinal cancer.
abstract: BACKGROUND
  Numerous factors influence the development of gastrointestinal (GI) cancer. The insulin-like growth factor (IGF) axis plays a role in embryonic and postnatal growth and tissue repair. Elevated levels of IGFs, low levels of IGF binding proteins (IGFBPs) and over-expression of IGF receptor (IGFR-I) were associated with several stages of cancer. Here, the prevalence of the single nucleotide polymorphisms (SNPs) rs6214 in the IGF type I (IGF-I) gene and rs6898743 in the growth hormone receptor (GHR) gene in patients with GI cancer and controls was studied.
  
  
  METHODS
  In this Dutch case-control study, DNA isolated from blood of 1,457 GI cancer patients; 438 patients with head and neck cancer (HNC), 475 with esophageal cancer (EC) and 544 with colorectal cancer (CRC) and 1,457 matched controls, was used to determine the rs6214 and rs6898743 genotypes by polymerase chain reaction. The association between these SNPs and GI cancer, HNC, esophageal adenocarcinoma (EAC), esophageal squamous-cell carcinoma (ESCC) and proximal or distal CRC was studied. Odds ratios (ORs) with 95% confidence interval (95% CI) were calculated via unconditional logistic regression.
  
  
  RESULTS
  Overall for GI cancer, the ORs for SNPs rs6214 and rs6898743 were approximately 1.0 (p-value>0.05), using the most common genotypes GG as reference. An OR of 1.54 (95% CI, 1.05-2.27) was found for EC for genotype AA of rs6214. The ORs for EAC were 1.45 (95% CI, 1.04-2.01) and 1.71 (95% CI, 1.10-2.68), for genotypes GA and AA, respectively. Genotype GC of rs6898743 showed an OR of 0.47 (95% CI, 0.26-0.86) for ESCC.
  
  
  CONCLUSIONS
  The A allele of SNP rs6214 in the IGF-I gene was associated with EAC, and with HNC in women. The GC genotype of rs6898743 in the GHR gene was negatively associated with ESCC.
authors.affiliation: Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Jennie
authors.initials: J
authors.lastname: Ong
authors.affiliation: Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Jody
authors.initials: J
authors.lastname: Salomon
authors.affiliation: Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Rene H M
authors.initials: RH
authors.lastname: te Morsche
authors.affiliation: Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Hennie M J
authors.initials: HM
authors.lastname: Roelofs
authors.affiliation: Department of Gastroenterology, Hospital Gelderse Vallei, Ede, the Netherlands.
authors.forename: Ben J M
authors.initials: BJ
authors.lastname: Witteman
authors.affiliation: Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Polat
authors.initials: P
authors.lastname: Dura
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Lacko
authors.affiliation: Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Wilbert H M
authors.initials: WH
authors.lastname: Peters
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011986:Receptors, Somatotropin / Q000235:genetics*; D012737:Sex Factors
chemical_list: D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I