title: Association between TGFBR1*6A and osteosarcoma: a Chinese case-control study.
abstract: BACKGROUND
  TGFBR1*6A is a common hypomorphic variant of transforming growth factor beta receptor 1 (TGFBR1). TGFBR1*6A is associated with an increased cancer risk, but the association of this polymorphism with osteosarcoma remains unknown. We have measured the frequency of TGFBR1*6A variants in osteosarcoma cases and controls.
  
  
  METHODS
  Our case-control study is based on 168 osteosarcoma patients and 168 age- and gender-matched controls. Blood samples were obtained and the TGFBR1*6A variant determined by PCR amplification and DNA sequencing. The odds ratio (OR) and 95% confidence interval (95% CI) for the TGFBR1*6A polymorphism were calculated by unconditional logistic regression, adjusted for both age and gender. Three models - dominant, additive and recessive - were used to analyze the contribution of the TGFBR1*6A variant to osteosarcoma susceptibility.
  
  
  RESULTS
  Heterozygotic and homozygotic TGFBR1*6A variants represented 50.4% and 6.0% of the 168 cases, whereas the controls had 18. 5% and 1.3%, respectively. ORs for homozygosity and heterozygosity of the TGFBR1*6A allele were 4.6 [95% CI, 2.33-7.97] and 2.9 [95% CI, 1.59-5.34] in the additive model. There were significant increases in the TGFBR1*6A variants in osteosarcoma cases compared to control in all 3 models. Further analysis showed that TGFBR1*6A genotypes were not associated with gender, age, or tumor location. However, TGFBR1*6A was significantly associated with less metastasis.
  
  
  CONCLUSIONS
  TGFBR1*6A, a dominant polymorphism of TGFBR1, is associated with increased susceptibility and metastasis spread of osteosarcoma.
authors.affiliation: Center of Orthopaedic Surgery, Orthopaedic Oncology Institute of PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, China. huys11@sina.com
authors.forename: Yun-Sheng
authors.initials: YS
authors.lastname: Hu
authors.forename: Yong
authors.initials: Y
authors.lastname: Pan
authors.forename: Wen-Hai
authors.initials: WH
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Ma
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001859:Bone Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D012516:Osteosarcoma / Q000208:ethnology / Q000235:genetics* / Q000556:secondary; D010641:Phenotype; 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*; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
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