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Relationship between Genetic Susceptibility of Non-Small Cell Lung Cancer and TGF-BetaRI Gene

TGF-betaRI gene is a tumor-suppressing gene. The loss of its biological activity due to the mutation of this gene has been found in a variety of human tumors.To investigate whether the transforming growth factor-beta receptor type I(TGF-betaRI) gene is associated with genetic predisposition of primary non-small cell lung cancer (NSCLC). The entire coding region of TGF-betaRI and flanking intron sequences from 53 NSCLC tissues were examined for alterations using SSCP and direct sequencing. Results show that no somatic point mutations other than two silent mutations and a polymorphism were found in the TGF-betaRI gene. The two silent mutations located at codon 544 (AAT to AAC) and codon 406 (TTA to CTA), respectively, and the polymorphism was at 24 base of intron7 (G to A). Interestingly, we found that the subjects with homozygous genotype A/A displayed more than threefold increased risk of developing NSCLC than the common wild genotype G/G. As the first report, this study showed that TGF-betaRI gene is not a frequent site of spontaneous mutational inactivation while the detected polymorphism could be a susceptibility allele that predisposes to carcinogenesis of NSCLC.