title: Int7G24A variant of transforming growth factor-beta receptor type I is associated with invasive breast cancer.
abstract: OBJECTIVE
  The transforming growth factor-beta (TGF-beta) signaling pathway has been frequently implicated in breast cancer. An intronic variant (Int7G24A) of TGF-beta receptor type I (TGFBR1) is associated with kidney and bladder cancers in our recent study. We hypothesize that this germline variant may be involved in development and progression of breast cancer.
  
  
  METHODS
  Case-control studies were designed from archived paraffin-embedded tissue specimens from the same geographic area with a homogenous ethnic population. We analyzed 223 patients (25 with preinvasive tumors and 198 with invasive and metastatic breast cancers) and 153 noncancer controls. The Int7G24A was identified by PCR-RFLP. Another germline deletion (TGFBR1*6A) and somatic mutations in the TGFBR1 were also analyzed by PCR and single-strand conformational polymorphism.
  
  
  RESULTS
  The Int7G24A allele was evident in 32% of patients with preinvasive neoplasms and 48% of patients with invasive breast cancers compared with 26% controls (P = 0.00008). In addition, 11 (5.6%) homozygous Int7G24A carriers were found in patients with invasive breast cancers, whereas only 3 (2%) homozygous carriers were found in the control group. The TGFBR1*6A allele was not significantly associated with breast cancer patients and only one somatic mutation was found in 71 breast cancers.
  
  
  CONCLUSIONS
  These data suggest that the germline Int7G24A variant may represent a risk factor for invasive breast cancer and a marker for breast cancer progression. A separate study with a larger sample size is warranted to validate the association of the Int7G24A with human breast cancer.
authors.affiliation: Wood Hudson Cancer Research Laboratory, 931 Isabella Street, Newport, KY 41071-4701, USA. tchen@woodhudson.org
authors.forename: Taiping
authors.initials: T
authors.lastname: Chen
authors.forename: Chad R
authors.initials: CR
authors.lastname: Jackson
authors.forename: Andrew
authors.initials: A
authors.lastname: Link
authors.forename: Michael P
authors.initials: MP
authors.lastname: Markey
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Colligan
authors.forename: Larry E
authors.initials: LE
authors.lastname: Douglass
authors.forename: Jackson O
authors.initials: JO
authors.lastname: Pemberton
authors.forename: James A
authors.initials: JA
authors.lastname: Deddens
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Graff
authors.forename: Julia H
authors.initials: JH
authors.lastname: Carter
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human