FGFR4 genetic polymorphisms determine the chemotherapy response of Chinese patients with non-small cell lung cancer

Abstract

Aim: To investigate the relationship of fibroblast growth factor receptor 4 (FGFR4) gene polymorphisms with the response of Chinese patients with non-small cell lung cancer (NSCLC) to chemotherapy. Methods: A total of 629 patients with Stage III (A+B) or IV NSCLC, as well as 729 age-and gender-matched healthy controls were recruited. All the patients received platinum-based chemotherapy, and the therapeutic effects were evaluated. Three polymorphisms in the FGFR4 gene (rs351855G/A, rs145302848C/G, and rs147603016G/A) were genotyped, and the association between the 3 polymorphisms and the chemotherapy effect was analyzed using SPSS software, version 16.0. Results: The genotype frequencies of rs145302848C/G and rs147603016G/A were not significantly different between NSCLC patients and healthy controls on one hand, and between the responders and non-responders to the chemotherapy on the other hand. The distribution of AA genotype and A-allele of rs351855G/A was significantly lower in NSCLC patients than in healthy controls. Using patients with the GG genotype as a reference, the AA carrier had a significantly reduced risk for the development of NSCLC after normalizing to age, sex and smoking habits. In NSCLC patients, this genotype occurred more frequently in the responders to the chemotherapy than in non-responders. The chance of being a responder was significantly increased with the AA genotype as compared to G genotype. The AA genotype of rs351855G/A had a better prognosis compared with GA and GG genotype carriers: the overall survival of patients with the AA genotype of rs351855G/A was significantly longer than those with the GG+GA genotype (21.1 vs 16.5 months). Conclusion:The rs351855G/A polymorphisms of FGFR4 gene can be used to predict the occurrence, chemotherapy response and prognosis of NSCLC.

The FGFR4-388arg Variant Promotes Lung Cancer Progression by N-Cadherin Induction

“…However, contradictory results have been reported in other studies. In a work involving advanced NSCLC Asian patients, the FGFR4-388Arg variant correlated with better outcome 17 , and in another study involving Caucasian NSCLC patients, no association between this FGFR4 variant and outcome was found 18 . In some retrospective studies of lung cancer cohorts analyzing each histological subtype independently, the FGFR4-388Arg variant was linked to lymph node involvement and poorer overall survival (OS) in ADC patients 13 , 16 , 18 , 19 .…”

Influence of NOS3 rs2070744 genotypes on hepatocellular carcinoma patients treated with lenvatinib

“…Moreover, the FGFR4 rs351855 CT/TT genotypes sustained receptor activation and improved stability of the receptor more than did the CC genotype. This suggested influence on the response to chemotherapy in HCC patients treated with tyrosine kinase inhibitors [21][22][23][24] .…”

Prognostic Role of the FGFR4-388Arg Variant in Lung Squamous-Cell Carcinoma Patients With Lymph Node Involvement

“…The role of the FGFR4-388Arg variant as a prognostic factor in lung cancer has been previously addressed in the literature, but little work has focused on the role of this variant in SCC patients. In several cohorts jointly analyzing ADC and SCC patients, controversial results have been reported, [12][13][14] probably as a result of the different ethnicities and clinicopathologic characteristics of the patients included in these study cohorts. Nevertheless, none of these studies analyzed SCC patients independently.…”

“…However, the implications of this variant in patient prognosis seem to be controversial in studies that jointly analyze multiple histologic subtypes of NSCLC. [12][13][14] Nonetheless, other studies that analyze the different NSCLC subhistologic types individually have shown that the FGFR4-388Arg variant is related to poorer overall survival (OS) in several cohorts of ADC patients. 15,16 In an SCC patient cohort analysis, however, the correlation between this variant and outcome was not clear.…”