title: Lack of an association between the TGFBR1*6A variant and colorectal cancer risk.
abstract: OBJECTIVE
  Recently a common variant of the TGFBR1 gene, TGFBR1*6A, has been proposed to act as a low-penetrance tumor susceptibility allele for colorectal cancer, but data from published studies with individually low statistical power are conflicting. To further evaluate the relationship between TGFBR1*6A and colorectal cancer risk, we have conducted a large case-control study and a meta-analysis of previously published studies.
  
  
  METHODS
  A total of 1,042 colorectal cancer cases and 856 population controls were genotyped for the TGFBR1*6A polymorphism. Previously published case-control studies of the relationship between TGFBR1*6A and colorectal cancer were identified, and a meta-analysis was conducted.
  
  
  RESULTS
  We found no evidence that homozygosity, heterozygosity or carrier status for the TGFBR1*6A allele confers an increased risk of colorectal cancer; respective odds ratios (OR) were 1.05 [95% confidence interval (95% CI), 0.83-1.32], 0.82 (95% CI, 0.34-1.99), and 0.92 (95% CI, 0.74-1.15), respectively. A meta-analysis of our case-control study and seven other studies that provided data on 2,627 colorectal cancer cases and 3,387 controls also yielded no evidence that possession of the TGFBR1*6A allele is associated with an elevated risk of colorectal cancer; pooled estimate of the OR were 1.20 (95% CI, 0.64-2.24) for homozygosity, 1.11 (95% CI, 0.96-1.29) for heterozygosity, and 1.13 (95% CI, 0.98-1.30) for carriers of TGFBR1*6A.
  
  
  CONCLUSIONS
  Current data provide limited support for the hypothesis that sequence variation in TGFBR1 defined by the TGFBR1*6A allele confers an elevated risk of colorectal cancer.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Skoglund
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.forename: Johan
authors.initials: J
authors.lastname: Dalén
authors.forename: Stefan
authors.initials: S
authors.lastname: Dedorson
authors.forename: David
authors.initials: D
authors.lastname: Edler
authors.forename: Fredrik
authors.initials: F
authors.lastname: Hjern
authors.forename: Jörn
authors.initials: J
authors.lastname: Holm
authors.forename: Claes
authors.initials: C
authors.lastname: Lenander
authors.forename: Ulrik
authors.initials: U
authors.lastname: Lindforss
authors.forename: Nils
authors.initials: N
authors.lastname: Lundqvist
authors.forename: Hans
authors.initials: H
authors.lastname: Olivecrona
authors.forename: Louise
authors.initials: L
authors.lastname: Olsson
authors.forename: Lars
authors.initials: L
authors.lastname: Påhlman
authors.forename: Jörgen
authors.initials: J
authors.lastname: Rutegård
authors.forename: Kennet
authors.initials: K
authors.lastname: Smedh
authors.forename: Anders
authors.initials: A
authors.lastname: Törnqvist
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.forename: Annika
authors.initials: A
authors.lastname: Lindblom
mesh_terms: D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012307:Risk Factors
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human