Association between the T29-->C polymorphism in the transforming growth factor beta1 gene and breast cancer among elderly white women: The Study of Osteoporotic Fractures.
BACKGROUND
Transgenic animal experiments suggest that increased expression of transforming growth factor beta1 (TGF-beta1) is protective against early tumor development, particularly in breast cancer. A T-->C (thymine to cytosine) transition in the 29th nucleotide in the coding sequence results in a leucine to proline substitution at the 10th amino acid and is associated with increased serum levels of TGF-beta1.


OBJECTIVE
To determine whether an association exists between this TGF-beta1 polymorphism and breast cancer risk.


METHODS
The Study of Osteoporotic Fractures, a prospective cohort study of white, community-dwelling women aged 65 years or older who were recruited at 4 US centers between 1986 and 1988. Three thousand seventy-five women who provided sufficient clinical information, buffy coat samples, and adequate consent for genotyping are included in this analysis.


METHODS
Breast cancer cases during a mean (SD) follow-up of 9.3 (1.9) years, verified by medical chart review and compared by genotype.


RESULTS
Risk of breast cancer was similar in the 1124 women with the T/T genotype (56 cases; 5.4 per 1000 person-years) and the 1493 women with the T/C genotype (80 cases; 5.8 per 1000 person-years) but was significantly lower (P =.01) in the 458 women with the C/C genotype (10 cases; 2.3 per 1000 person-years). In analyses that adjusted for age, age at menarche, age at menopause, estrogen use, parity, body mass index, and bone mineral density, women with the C/C genotype had a significantly lower risk of developing breast cancer compared with women with the T/T or T/C genotype (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.17-0.75). There was no significant difference between the risk for women with the T/C genotype compared with women with the T/T genotype (adjusted HR, 1.04; 95% CI, 0.73-1.48).


CONCLUSIONS
Our findings suggest that TGF-beta1 genotype is associated with risk of breast cancer in white women aged 65 years or older. Because the T allele is the common variant and confers an increased risk, it may be associated with a large proportion of breast cancer cases.
Ziv
E
E
Division of General Internal Medicine, Veterans Affairs Medical Center, Box 111-A1, 4150 Clement St, San Francisco, CA 94122, USA. eziv@itsa.ucsf.edu
Cauley
J
J
Morin
P A
PA
Saiz
R
R
Browner
W S
WS
D000368:Aged; D019943:Amino Acid Substitution; D015992:Body Mass Index; D015519:Bone Density; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D003596:Cytosine; D005260:Female; D005838:Genotype; D006801:Humans; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012307:Risk Factors; D013941:Thymine; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D044465:White People / Q000235:genetics
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003596:Cytosine; D013941:Thymine