Association of TGFB1 -509 C>T polymorphism with breast cancer: evidence from a meta-analysis involving 23,579 subjects

Breast Cancer Res Treat. 2010 Nov;124(1):243-9. doi: 10.1007/s10549-010-0832-0. Epub 2010 Mar 16.

Abstract

Although a number of genetic studies have attempted to link transforming growth factor beta 1 gene (TGFB1) -509 C>T polymorphism to breast cancer, the results were often irreproducible. We therefore aimed to meta-analyze all available case-control studies from the English-published literature to explore the association of this polymorphism with breast cancer. A total of 6 studies with 9 populations involving 10,197 patients and 13,382 controls were identified as of February 20, 2010. A random-effects model was performed irrespective of the between-study heterogeneity. Study quality was assessed in duplicate. The frequencies of TGFB1 -509 T allele in patients and controls ranged from 21.72 to 51.74%, and 24.53 to 52.40%, respectively. The presence of -509 T allele conferred a nonsignificant protective effect on breast cancer [odds ratio (OR) = 0.99; 95% confidence interval (CI) 0.93-1.05; P = 0.72]. This lack of association persisted under co-dominant, dominant, and recessive models. However, exclusion of the initial study significantly strengthened the magnitude of this protective effect. For example, under the dominant assumption, carriers of -509 T allele had a moderate reduced risk for breast cancer compared with the -509 CC homozygous (OR = 0.94; 95% CI 0.88-1.00; P = 0.04). Subgroup analyses by study designs and geographic areas did not substantially affect the present associations. No publication biases were observed by the fail-safe number. Taken together, our results demonstrated that TGFB1 -509 T allele was associated with a reduced risk to develop breast cancer and this allele appeared to act in an additive mode.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • Chi-Square Distribution
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polymorphism, Genetic*
  • Risk Assessment
  • Risk Factors
  • Transforming Growth Factor beta1 / genetics*

Substances

  • TGFB1 protein, human
  • Transforming Growth Factor beta1