Association between the T29→C polymorphism in the transforming growth factor β1 gene and breast cancer among elderly white women the study of osteoporotic fractures

被引:104
作者
Ziv, E
Cauley, J
Morin, PA
Saiz, R
Browner, WS
机构
[1] Vet Affairs Med Ctr, Div Gen Internal Med, San Francisco, CA 94122 USA
[2] Univ Calif San Francisco, Dept Med, San Francisco, CA USA
[3] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA
[4] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA
[5] Axys Pharmaceut Inc, La Jolla, CA USA
来源
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2001年 / 285卷 / 22期
关键词
D O I
10.1001/jama.285.22.2859
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context 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. Design, Setting, and Participants 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. Main Outcome Measure 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.
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页码:2859 / 2863
页数:5
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