title: TGFBR1*6A and cancer risk: a meta-analysis of seven case-control studies.
abstract: OBJECTIVE
  TGFBR1*6A is a hypomorphic polymorphic allele of the type I transforming growth factor beta receptor (TGFBR1). TGFBR1*6A is a candidate tumor susceptibility allele that has been associated with an increased incidence of various types of cancer. This study was undertaken to analyze all published case-control studies on TGFBR1*6A and cancer and determine whether TGFBR1*6A is associated with cancer.
  
  
  METHODS
  All published case-control studies assessing the germline frequency of TGFBR1*6A were included. Studies assessing TGFBR1*6A in tumors were excluded. The results of seven studies comprising 2,438 cases and 1,846 controls were pooled and analyzed.
  
  
  RESULTS
  Overall, TGFBR1*6A carriers have a 26% increased risk of cancer (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.07 to 1.49). Cancer risk for TGFBR1*6A homozygotes (OR, 2.53; 95% CI, 1.39 to 4.61) is twice that of TGFBR1*6A heterozygotes (OR, 1.26; 95% CI, 1.04 to 1.51). Analysis of various types of tumors shows that TGFBR1*6A carriers are at increased risk of developing breast cancer (OR, 1.48; 95% CI, 1.11 to 1.96), hematological malignancies (OR, 1.70; 95% CI, 1.13 to 2.54), and ovarian cancer (OR, 1.53; 95% CI, 1.07 to 2.17). Carriers of TGFBR1*6A who are from the United States are at increased risk of colorectal cancer (OR, 1.38; 95% CI, 1.02 to 1.86). However, Southern European TGFBR1*6A carriers have no increased colorectal cancer risk. There is no association between TGFBR1*6A and bladder cancer.
  
  
  CONCLUSIONS
  TGFBR1*6A is emerging as a highfrequency, low-penetrance tumor susceptibility allele that predisposes to the development of breast, ovarian, and colorectal cancer, as well as hematologic malignancies.
authors.affiliation: Cancer Genetics Program, Division of Hematology/Oncology, Evanston Northwestern Healthcare, Chicago, IL, USA.
authors.forename: Virginia G
authors.initials: VG
authors.lastname: Kaklamani
authors.forename: Nanjiang
authors.initials: N
authors.lastname: Hou
authors.forename: Yiansong
authors.initials: Y
authors.lastname: Bian
authors.forename: Jennifer
authors.initials: J
authors.lastname: Reich
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Loren S
authors.initials: LS
authors.lastname: Michel
authors.forename: W S
authors.initials: WS
authors.lastname: Rubinstein
authors.forename: Alfred
authors.initials: A
authors.lastname: Rademaker
authors.forename: Boris
authors.initials: B
authors.lastname: Pasche
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta