FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung
FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung
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DOI：
10.1002/ijc.24302
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发表时间：
2009-06-15
影响因子：
6.4
通讯作者：
Dragani, Tommaso A.
中科院分区：
文献类型：
--
作者：
Falvella, Felicia S.;Frullanti, Elisa;Dragani, Tommaso A.
成纤维细胞生长因子受体4（FGFR 4）Gly 388 Arg多态性与541例意大利肺腺癌（ADCA）患者的临床分期和总生存率的相关性表明，与Gly/Gly纯合子患者相比，携带罕见Arg 388等位基因的患者的生存率显著降低[风险比（HR）= 1.5; 95%可信区间（CI）1.1-1.9]，降低与相同多态性与临床分期相关（HR = 1.8，95% CI 1.3-2.6）。相比之下，在挪威肺ADCA患者或意大利肺鳞状细胞癌（SQCC）患者的小系列中未检测到显著相关性。肺中表达的已知FGFR 4配体（FGF 9、FGF 18和FGF 19）的单核苷酸多态性与临床分期或生存期无关，且与FGFR 4无相互作用。根据FGFR 4基因型分析正常肺中的基因表达谱，表明与等位基因携带状态相关的特定转录模式，表明FGFR 4多态性在正常肺中已经可检测到的功能作用。这些发现证实了意大利肺ADCA人群中FGFR 4 Gly 388 Arg多态性与临床分期和总生存期的显著相关性，并证明了正常肺组织中存在FGFR 4基因型依赖性转录谱。(C)2009年UICC
The association of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism with clinical stage and overall survival in a series of 541 Italian lung adenocarcinoma (ADCA) patients indicated a significantly decreased survival in patients carrying the rare Arg388 allele as compared to that in Gly/Gly homozygous patients [hazard ratio (HR) = 1.5; 95% confidence interval (CI) 1.1-1.9], with the decrease related to the association of the same polymorphism with clinical stage (HR = 1.8, 95% CI 1.3-2.6). By contrast, no significant association was detected in small series of either Norwegian lung ADCA patients or Italian lung squamous cell carcinoma (SQCC) patients. Single nucleotide polymorphisms of known FGFR4 ligands expressed in lung (FGF9, FGF18 and FGF19) were not associated with clinical stage or survival and showed no interaction with FGFR4. Analysis of gene expression profile in normal lungs according to FGFR4 genotype indicated a specific transcript pattern associated with the allele carrier status, suggesting a functional role for the FGFR4 polymorphism already detectable in normal lung. These findings confirm the significant association of the FGFR4 Gly388Arg polymorphism with clinical stage and overall survival in an Italian lung ADCA population and demonstrate a FGFR4 genotype-dependent transcriptional profile present in normal lung tissue. (C) 2009 UICC