title: Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites.
abstract: OBJECTIVE
  Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)( n ) repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor-binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study.
  
  
  METHODS
  Participants were African Americans (231 cases and 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5'-exonuclease (Taqman) assay. The IGF-I (CA)(n) repeat was assayed by PCR and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by logistic regression.
  
  
  RESULTS
  The IGF-I (CA)( 19 ) repeat was higher in White controls (50 %) than African American controls (31 %). Whites homozygous for the IGF-I (CA)(19) repeat had a nearly twofold increase in risk of colon cancer (OR = 1.77; 95 % CI = 1.15-2.73), but not African Americans (OR = 0.73, 95 % CI 0.50-1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR = 0.49, 95 % CI 0.28-0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p-trend <0.05).
  
  
  CONCLUSIONS
  These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans.
authors.affiliation: Department of Medicine, Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, Chapel Hill, 27599-7032, USA. tokeku@med.unc.edu
authors.forename: Temitope O
authors.initials: TO
authors.lastname: Keku
authors.forename: Adriana
authors.initials: A
authors.lastname: Vidal
authors.forename: Shannon
authors.initials: S
authors.lastname: Oliver
authors.forename: Catherine
authors.initials: C
authors.lastname: Hoyo
authors.forename: Ingrid J
authors.initials: IJ
authors.lastname: Hall
authors.forename: Oluwaseun
authors.initials: O
authors.lastname: Omofoye
authors.forename: Maya
authors.initials: M
authors.lastname: McDoom
authors.forename: Kendra
authors.initials: K
authors.lastname: Worley
authors.forename: Joseph
authors.initials: J
authors.lastname: Galanko
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
authors.forename: Robert
authors.initials: R
authors.lastname: Millikan
mesh_terms: D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism; D001741:Black or African American / Q000235:genetics; D000368:Aged; D002096:C-Peptide / Q000097:blood; D003110:Colonic Neoplasms / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D052242:Adiponectin; D002096:C-Peptide; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II