Original Article

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

Hong-mei Fang, Gang Tian, Li-juan Zhou, Han-ying Zhou, Ying-zhi Fang
DOI: 10.1038/aps.2012.206


Hong-mei FANG1, #, Gang TIAN2, #, Li-juan ZHOU1, Han-ying ZHOU1, Ying-zhi FANG1, *

1Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; 2Department of Stomatology, Changhai Hospital Affiliated to the Second Military Medicine College, Shanghai 200433, China

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.

Keywords: non-small cell lung cancer; platinum-based chemotherapy; fibroblast growth factor receptor 4; gene polymorphism; response to chemotherapy; prognosis; Chinese population

# These authors contributed equally to this article.
* To whom correspondence should be addressed.
E-mail fangyz2012@gmail.com
Received 2012-09-26 Accepted 2012-12-31

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