Association between TGFBR1*6A and osteosarcoma: a Chinese case-control study.
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.
Hu
Yun-Sheng
YS
Center of Orthopaedic Surgery, Orthopaedic Oncology Institute of PLA, Tangdu Hospital, Fourth Military Medical University, Xi'an, China. huys11@sina.com
Pan
Yong
Y
Li
Wen-Hai
WH
Zhang
Yong
Y
Li
Jun
J
Ma
Bao-An
BA
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
D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human