[Correlations of polymorphisms of TGFB1 and TGFBR2 genes to genetic susceptibility to gastric cancer].
OBJECTIVE
Transforming growth factor beta (TGFbeta) signaling pathway plays an important role in the genesis and progression of tumors through regulating cell proliferation and differentiation. The concentration of TGFbeta1 in plasma and the expression of TGFbeta receptor II (TGFbetaRII) are correlated to the development of certain tumors, including gastric cancer. This study was to explore the correlations of functional genetic variants in TGFB1 and TGFBR2 genes to the genetic susceptibility to gastric cancer.


METHODS
A case-control study was conducted in Yixing City, a high incidence area of gastric cancer. Polymorphisms of TGFB1 C-509T, TGFB1 Leu10Pro, and TGFBR2 G-875A in 256 gastric cancer patients and 303 cancer-free controls, frequency-matched by age and sex, were determined by primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR). Crude and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were measured by multivariate Logistic regression analysis to evaluate the correlations of the polymorphisms to the susceptibility to gastric cancer.


RESULTS
The TGFB1 C-509T and TGFB1 Leu10Pro were in high linkage disequilibrium (D'=0.86). Compared with wild-type homogenous genetypes -509CC and 10 Leu/Leu, variant genetypes -509CT/TT, 10 Leu/Pro, and 10 Pro/Pro decreased the risk of gastric cancer by 49% and 34% (adjusted OR=0.51, 95% CI=0.36-0.74 for -509CT/TT; adjusted OR=0.66, 95% CI=0.45-0.98 for 10 Leu/Pro or 10 Pro/Pro). The risk of gastric cancer was decreased along with the number of variant sites in the TGFB1 C-509T and TGFBR2 G-875A (Chi(2)=15.70,P < 0.001). Stratified analysis showed that the protective effects of the genotypes were obvious in the subjects of no more than 60-year old (OR=0.42, 95% CI=0.23-0.79) and in non-drinkers (OR=0.45, 95% CI=0.27-0.74).


CONCLUSIONS
Genetic variants of TGFB1 and TGFBR2 genes may contribute to the risk of developing gastric cancer in an eastern Chinese population in Yixing city.
Zhou
Yan
Y
Department of Oncology, People's Hospital of Yixing City, Yixing, Jiangsu 214200, P. R. China.
Jin
Guang-Fu
GF
Jiang
Guo-Jun
GJ
Wang
Hong-Min
HM
Tan
Yong-Fei
YF
Ding
Wei-Liang
WL
Wang
Li-Na
LN
Chen
Wen-Sen
WS
Ke
Qiao
Q
Shen
Jing
J
Xu
Yao-Chu
YC
Shen
Hong-Bing
HB
D000367:Age Factors; D000428:Alcohol Drinking; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II