title: Constitutively decreased TGFBR1 allelic expression is a common finding in colorectal cancer and is associated with three TGFBR1 SNPs.
abstract: OBJECTIVE
  Constitutively decreased TGFBR1 allelic expression is emerging as a potent modifier of colorectal cancer risk in mice and humans. This phenotype was first observed in mice, then in lymphoblastoid cell lines from patients with microsatellite stable colorectal tumors.
  
  
  METHODS
  We assessed the frequency of constitutively decreased TGFBR1 allelic expression and association with SNPs covering the TGFBR1 locus using RNA and DNA extracted from the peripheral blood lymphocytes of 118 consecutive patients with biopsy-proven adenocarcinoma of the colon or the rectum.
  
  
  RESULTS
  We found that 11(9.3%) of 118 patients exhibited decreased TGFBR1 allelic expression (TGFBR1 ASE). TGFBR1 ASE was strongly associated with three SNPs in linkage disequilibrium with each other: rs7034462 (p = 7.2 x 10-4), TGFBR1*6A (p = 1.6 x 10-4) and rs11568785 (p = 1.4 x 10-4).
  
  
  CONCLUSIONS
  These results confirm the high prevalence of constitutively decreased TGFBR1 allelic expression among patients with colorectal cancer. The association of this phenotype with TGFBR1*6A, rs7034462 and rs1156875 suggests an association between TGFBR1 SNPs and colorectal cancer, which warrants additional studies.
authors.affiliation: Division of Hematology/Oncology, The University of Alabama at Birmingham and UAB Comprehensive Cancer Center, Birmingham, AL 35203, USA. boris.pasche@ccc.uab.edu
authors.forename: Boris
authors.initials: B
authors.lastname: Pasche
authors.forename: Kari B
authors.initials: KB
authors.lastname: Wisinski
authors.forename: Maureen
authors.initials: M
authors.lastname: Sadim
authors.forename: Virginia
authors.initials: V
authors.lastname: Kaklamani
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pennison
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zeng
authors.forename: Naresh
authors.initials: N
authors.lastname: Bellam
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Zimmerman
authors.forename: Nengjun
authors.initials: N
authors.lastname: Yi
authors.forename: Kui
authors.initials: K
authors.lastname: Zhang
authors.forename: John
authors.initials: J
authors.lastname: Baron
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: M Geoffrey
authors.initials: MG
authors.lastname: Hayes
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D003430:Cross-Sectional Studies; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse