非小细胞肺癌的遗传易感性与转化生长因子-β受体Ⅰ基因的关系

Relationship between genetic susceptibility of non-small cell lung cancer and the TGF-βRI gene

目的探讨转化生长因子-β受体Ⅰ（TGF-βRI）基因与非小细胞肺癌（NSCLC）遗传易感性的关系。方法采用单链构象多态性分析（SSCP）和DNA测序方法，观察53例原发性NSCLC组织的TGF—βRI基因的整个密码区域以及旁侧内含子序列的改变。结果未见任何体细胞水平的突变，但在TGF—βRI基因中发现了两个沉默突变和一个多态性位点。两个沉默突变分别位于密码子的344位（由ATT突变成AAC）和密码子的406位（由TTA突变成CTA）。多态性位点位于该基因的第7号内含子中的第24位核苷酸处（由G突变成A）。根据病例组和对照组分析，可见纯合基因型A／A携带者患非小细胞肺癌的风险比野生基因型G／G的携带者高出3倍以上。结论TGF-βRI基因虽然不是自发突变失活的频繁位点，但是此处研究的多态性可能具有NSCLC的遗传易感性。

Objective To-investigate whether the transforming growth factor-beta receptor type Ⅰ （TGF-βRI） gene is associated with genetic predisposition of primary non-small cell lung cancer （NSCLC）. Methods The entire coding region of TGF-βRI and flanking intron sequences from 53 NSCLC tissues were examined for alterations using SSCP and direct sequencing. Results No somatic point muta- tions other than two silent mutations and a polymorphism were found in the TGF-βRI 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 th 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. Conclusion As the first report,this study showed that TGF-βRI 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.