Genetic polymorphisms of TGF-beta1 & TNF-beta and breast cancer risk.
OBJECTIVE
The proliferation of malignant breast epithelial cells is regulated by various stimuli including cytokines and growth factors, thus the variants of those genes may modify the breast cancer risk. To evaluate the potential influences of TGF-beta1 T29C and TNF-beta A252G gene polymorphisms on breast cancer risk, a case-control study was conducted in Korea.


METHODS
Histologically confirmed breast cancer cases (n=560) and controls (n=509) with no previous history of cancer were recruited from three teaching hospitals in Seoul, Korea. Genotypes were determined by PCR-CTPP (polymerase chain reaction with confronting two-pair primers) method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression model adjusting for age, body mass index, education, parity, age at first full-term pregnancy, and family history of breast cancer.


RESULTS
The TGF-beta1 29C-allele containing genotypes posed an increased risk of breast cancer (OR=1.3, 95% CI=1.02-1.79), especially in postmenopausal women (OR=1.6, 95% CI=1.01-2.44). Similarly, the TNF-beta 252G-allele containing genotypes posed an increased risk of postmenopausal breast cancer (OR=1.7, 95% CI=1.09-2.55). The risk of postmenopausal breast cancer increased in parallel with the number of the risk genotypes (p for trend <0.01). When data were stratified by the presumed non-genetic risk factors, TGF-beta1 C-allele containing genotypes were found to increase breast cancer risk almost two-fold in postmenopausal women with greater than median body mass index (>22.8 kg/m2) (OR=1.9, 95% CI=1.04-3.37).


CONCLUSIONS
The results of this study therefore suggest that polymorphisms of TGF-beta1 and TNF-beta genes may modify individual susceptibility to breast cancer in Korean women.
Lee
Kyoung-Mu
KM
Department of Preventive Medicine, Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-799, Korea.
Park
Sue Kyung
SK
Hamajima
Nobuyuki
N
Tajima
Kazuo
K
Yoo
Keun-Young
KY
Shin
Aesun
A
Noh
Dong-Young
DY
Ahn
Sei-Hyun
SH
Hirvonen
Ari
A
Kang
Daehee
D
D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D007723:Korea / Q000453:epidemiology; D016013:Likelihood Functions; D016014:Linear Models; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause; D017697:Premenopause; D012306:Risk; D016212:Transforming Growth Factor beta / Q000235:genetics*
D008233:Lymphotoxin-alpha; D016212:Transforming Growth Factor beta