title: Common genetic variation within IGFI, IGFII, IGFBP-1, and IGFBP-3 and endometrial cancer risk.
abstract: OBJECTIVE
  The insulin-like growth factor (IGF) pathway plays a critical role in the growth and development of the uterus and is believed to function as a mediator of steroid hormone actions in the endometrium. The local expression of genes encoding IGFs and IGF-binding proteins (IGFBPs) is important in determining IGF bioactivity in the uterus. Genetic variation in key genes within the IGF pathway may influence the rate of cellular proliferation and differentiation in the uterus and ultimately affect the risk of endometrial cancer. Our hypothesis is that variant alleles in key genes involved in the IGF pathway will influence the development of endometrial cancer.
  
  
  METHODS
  We conducted a case-control study nested within the Nurses' Health Study (NHS) and the Women's Health Study (WHS) to investigate the association between forty-four polymorphisms within IGFI, IGFII, IGFBP-1, and IGFBP-3 with endometrial cancer risk using 692 invasive endometrial cancer cases and 1723 matched controls. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the risk of endometrial cancer.
  
  
  RESULTS
  We observed an inverse association with IGFII rs3741211 and endometrial cancer risk (OR=0.79 (95% CI: 0.63, 0.99)) and IGFII rs1004446 and endometrial cancer risk (OR=0.80 (95% CI: 0.68, 0.94)). We also observed an inverse association with IGFBP-3 rs2453839 and endometrial cancer risk (OR=0.81 (95%CI: 0.67, 0.98). However, we did not observe any statistically significant associations with the polymorphisms in IGFI and IGFBP1 and endometrial cancer risk.
  
  
  CONCLUSIONS
  Genetic variation with IGFII and IGFBP-3 may influence endometrial cancer risk in Caucasians. Polymorphisms in IGFI and IGFBP-1 were not associated with endometrial cancer risk, but further research is needed.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: McGrath
authors.forename: I-Min
authors.initials: IM
authors.lastname: Lee
authors.forename: Julie
authors.initials: J
authors.lastname: Buring
authors.forename: Immaculata
authors.initials: I
authors.lastname: De Vivo
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II