Polymorphisms in TGF-beta1 gene and the risk of lung cancer.
BACKGROUND
Transforming growth factor-beta1 (TGF-beta1) functions as a suppressor of tumor initiation by inhibiting cellular proliferation or by promoting cellular differentiation or apoptosis in the early phase of cancer development. Variations in the DNA sequence in the TGF-beta1 gene may lead to altered TGF-beta1 production and/or activity, and so this can modulate an individual's susceptibility to lung cancer. To test this hypothesis, we investigated the association of the TGF-beta1 -509C > T and 869T > C (L10P) polymorphisms and their haplotypes with the risk of lung cancer in a Korean population.


METHODS
The TGF-beta1 genotypes were determined in 432 lung cancer patients and in 432 healthy control subjects who were frequency-matched for age and gender. The TGF-beta1 haplotypes were predicted using a Bayesian algorithm in the Phase program.


RESULTS
Individuals with at least one -509T allele were at a significantly decreased risk of adenocarcinoma (AC) and small cell carcinoma (SM), as compared with carriers with the -509CC genotype [adjusted odds ratio (OR), 0.63; 95% confidence interval (CI), 0.42-0.96; P = 0.04; and adjusted OR, 0.45; 95% CI, 0.27-0.76; P = 0.002; respectively]. For the 869T > C polymorphism, the combined TC + CC genotype was associated with a significantly decreased risk of SM compared with the TT genotype (adjusted OR, 0.52; 95% CI, 0.31-0.88; P = 0.01). Consistent with the results of the genotyping analyses, the -509T/869C haplotype was associated with a significantly decreased risk of AC and SM as compared with the -509C/869T haplotype (adjusted OR, 0.75; 95% CI, 0.57-0.98; P = 0.04; and adjusted OR, 0.67; 95% CI, 0.47-0.96; P = 0.02; respectively).


CONCLUSIONS
The TGF-beta1 -509C > T and 869T > C polymorphisms and their haplotypes may contribute to genetic susceptibility to AC and SM of the lung.
Kang
Hyo-Gyoung
HG
Cancer Research Institute, Kyungpook National University Hospital, Samduk 2Ga 50, Daegu 700-412, Republic of Korea.
Chae
Myung Hwa
MH
Park
Jung Min
JM
Kim
Eun Jin
EJ
Park
Jae Hyung
JH
Kam
Sin
S
Cha
Sung Ick
SI
Kim
Chang Ho
CH
Park
Rang-Woon
RW
Park
Sun Hee
SH
Kim
Yong Lim
YL
Kim
In-San
IS
Jung
Tae Hoon
TH
Park
Jae Yong
JY
D000230:Adenocarcinoma / Q000235:genetics*; D018287:Carcinoma, Large Cell / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1