title: Genetic variation in the transforming growth factor-β signaling pathway and survival after diagnosis with colon and rectal cancer.
abstract: BACKGROUND
  The transforming growth factor-β (TGF-β) signaling pathway is involved in many aspects of tumorigenesis, including angiogenesis and metastasis. The authors evaluated this pathway in association with survival after a diagnosis of colon or rectal cancer.
  
  
  METHODS
  The study included 1553 patients with colon cancer and 754 patients with rectal cancer who had incident first primary disease and were followed for a minimum of 7 years after diagnosis. Genetic variations were evaluated in the genes TGF-β1 (2 single nucleotide polymorphisms [SNPs]), TGF-β receptor 1 (TGF-βR1) (3 SNPs), smooth muscle actin/mothers against decapentaplegic homolog 1 (Smad1) (5 SNPs), Smad2 (4 SNPs), Smad3 (37 SNPs), Smad4 (2 SNPs), Smad7 (11 SNPs), bone morphogenetic protein 1 (BMP1) (11 SNPs), BMP2 (5 SNPs), BMP4 (3 SNPs), bone morphogenetic protein receptor 1A (BMPR1A) (9 SNPs), BMPR1B (21 SNPs), BMPR2 (11 SNPs), growth differentiation factor 10 (GDF10) (7 SNPs), Runt-related transcription factor 1 (RUNX1) (40 SNPs), RUNX2 (19 SNPs), RUNX3 (9 SNPs), eukaryotic translation initiation factor 4E (eiF4E) (3 SNPs), eukaryotic translation initiation factor 4E-binding protein 3 (eiF4EBP2) (2 SNPs), eiF4EBP3 (2 SNPs), and mitogen-activated protein kinase 1 (MAPK1) (6 SNPs).
  
  
  RESULTS
  After adjusting for American Joint Committee on Cancer stage and tumor molecular phenotype, 12 genes and 18 SNPs were associated with survival in patients with colon cancer, and 7 genes and 15 tagSNPs were associated with survival after a diagnosis of rectal cancer. A summary score based on "at-risk" genotypes revealed a hazard rate ratio of 5.10 (95% confidence interval, 2.56-10.15) for the group with the greatest number of "at-risk" genotypes; for rectal cancer, the hazard rate ratio was 6.03 (95% confidence interval, 2.83-12.75).
  
  
  CONCLUSIONS
  The current findings suggest that the presence of several higher risk alleles in the TGF-β signaling pathway increase the likelihood of dying after a diagnosis of colon or rectal cancer.
authors.affiliation: Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah 84108, USA. marty.slattery@hsc.utah.edu
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.forename: Abbie
authors.initials: A
authors.lastname: Lundgreen
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Herrick
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
authors.forename: Bette J
authors.initials: BJ
authors.lastname: Caan
mesh_terms: D000368:Aged; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012004:Rectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D015398:Signal Transduction / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta