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JAMA. 2001 Jun 13;285(22):2859-63.

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.

Author information

1
Division of General Internal Medicine, Veterans Affairs Medical Center, Box 111-A1, 4150 Clement St, San Francisco, CA 94122, USA. eziv@itsa.ucsf.edu

Erratum in

  • JAMA 2001 Dec 26;286(24):3081.

Abstract

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.

PMID:
11401606
DOI:
10.1001/jama.285.22.2859
[Indexed for MEDLINE]

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