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

JAMA. 2001 Jun 13;285(22):2859-63. doi: 10.1001/jama.285.22.2859.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Amino Acid Substitution
  • Body Mass Index
  • Bone Density
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Cytosine
  • European Continental Ancestry Group / genetics
  • Female
  • Genotype
  • Humans
  • Multivariate Analysis
  • Polymorphism, Genetic*
  • Proportional Hazards Models
  • Risk Factors
  • Thymine
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta1

Substances

  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Cytosine
  • Thymine