Polymorphisms in TGF-β1 gene and the risk of lung cancer

Background: Transforming growth factor-beta 1 (TGF-beta 1) functions as a suppressor of tumor initiation by inhibiting cellular proliferation or by promoting cellular differentiation or apoptosis in the early phase of cancer development. Variations in the DNA sequence in the TGF-beta 1 gene may lead to altered TGF-beta 1 production and/or activity, and so this can modulate an individual's susceptibitity to lung cancer. To test this hypothesis, we investigated the association of the TGF beta 1 -509C > T and 869T > C (L10P) polymorphisms and their haplotypes with the risk of lung cancer in a Korean population. Methods: The TGF-beta 1 genotypes were determined in 432 lung cancer patients and in 432 healthy control subjects who were frequency-matched for age and gender. The TGF-beta 1 haplotypes were predicted using a Bayesian algorithm in the Phase program. Results: Individuals with at least one -509T allele were at a significantly decreased risk of adenocarcinoma (AC) and small cell carcinoma (SM), as compared with carriers with the -509CC genotype [adjusted odds ratio (OR), 0.63; 95% confidence interval (CI), 0.42-0.96; P=0.04; and adjusted OR, 0.45; 95% CI, 0.27-0.76; P=0.002; respectively]. For the 869T > C polymorphism, the combined TC+CC genotype was associated with a significantly decreased risk of SM compared with the TT genotype (adjusted OR, 0.52; 95% CI, 0.31-0.88; P=0.01). Consistent with the results of the genotyping analyses, the -509T/869C haplotype was associated with a significantly decreased risk of AC and SM as compared with the -509C/869T haplotype (adjusted OR, 0.75; 95% CI, 0.57-0.98; P=0.04; and adjusted OR, 0.67; 95% CI, 0.47-0.96; P=0.02; respectively). Conclusion: The TGF-beta 1 -509C > T and 869T > C polymorphisms and their haplotypes may contribute to genetic susceptibility to AC and SM of the lung. (c) 2006 Elsevier Ireland Ltd. All rights reserved.