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

• Published in: Acta pharmacologica Sinica Vol. 34; no. 4; pp. 549 - 554
• Main Authors: Fang, Hong-mei, Tian, Gang, Zhou, Li-juan, Zhou, Han-ying, Fang, Ying-zhi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2013; Nature Publishing Group
• Subjects: Age; Aged; Antineoplastic Agents - therapeutic use; Asian Continental Ancestry Group; Biomedical and Life Sciences; Biomedicine; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Case-Control Studies; Female; Humans; Immunology; Internal Medicine; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Medical Microbiology; Middle Aged; Organoplatinum Compounds - therapeutic use; Original; original-article; Pharmacology/Toxicology; Polymorphism, Genetic; Receptor, Fibroblast Growth Factor, Type 4 - genetics; Vaccine; 中国; 化疗; 反应; 基因型频率; 基因多态性; 患者; 成纤维细胞生长因子受体; 非小细胞肺癌; non-small cell lung cancer; platinum-based chemotherapy; fibroblast growth factor receptor 4; response to chemotherapy; Chinese population; gene polymorphism; prognosis
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2012.206

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 com- pared to G genotype. The AA genotype of rs351855G/A had a better prognosis compared with GA and GG genotype carriers： the over- all 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.