Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed

Journal of Translational Medicine

Ignacio Gil-Bazo¹  Christian Rolfo³  Ana Patiño-García⁵  Leire Zubiri²  Patricia Martín⁴  María Rodríguez-Ruiz²  Marta Santisteban⁴  Víctor Collado¹  Josefa Salgado⁵  Inés López¹  Eduardo Castañón⁴  Estefanía Arévalo⁴ 

[1] Division of Oncology, Center for Applied Medical Research (CIMA), 31008 Pamplona, Spain;Department of Radiation Oncology, Clínica Universidad de Navarra, 31008 Pamplona, Spain;Oncology Department, Antwerp University Hospital UZA, 2650 Edegem, Belgium;Department of Oncology, Clínica Universidad de Navarra, 31008 Pamplona, Spain;Laboratory of Clinical Genetics, Clínica Universidad de Navarra, 31008 Pamplona, Spain

关键词: Non-small cell lung cancer;    Prognostic factors;    Predictive factors;    Epidermal growth factor receptor;    Polymorphisms;    Thymidylate synthase;   

Others  :  815030
DOI  :  10.1186/1479-5876-12-98

 received in 2013-11-03, accepted in 2014-04-07,  发布年份 2014

【 摘 要 】

Background

We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed.

Methods

Twenty-five patients treated with pemetrexed-based regimens were included. Genomic DNA was isolated prior to treatment. The variable number of tandem repeat (VNTR) polymorphisms, the G > C single nucleotide polymorphisms (SNP) and the TS 6-bp insertion/deletion (6/6) in the 3′ untranslated region (UTR) polymorphisms were analyzed and correlated with overall response rate (ORR), progression-free survival (PFS), overall-survival (OS) and toxicity.

Results

The genotype +6/+6 predicted a higher ORR among active/former smokers compared to +6/-6 genotype (100% vs. 50%; p = 0.085). Overall, the 3R/3R genotype predicted a higher ORR (100%) over the rest VNTR polymorphisms (p = 0.055). The presence of 3R/3R genotype significantly correlated with a superior ORR in patients without EGFR activating mutations (100%) compared to 2R/2R, 2R/3R and 3R/4R genotype (77.8%, 33.3% and 0% respectively; p = 0.017). After a median follow-up of 21 months, a trend towards a better PFS, although not significant, was found among subjects showing 3R/3R polymorphisms (p = 0.089). A significantly superior OS was found in patients showing 3R/3R genotype rather than other VNTR polymorphisms (p = 0.019). No significant correlation with the toxicity was observed.

Conclusion

In our series, 3R/3R polymorphism correlated with a superior OS. Also, this polymorphism, when associated to wild type EGFR, was related to a higher ORR to pemetrexed. Toxicity was not significantly correlated with a specific TS genotype.

【 授权许可】

   
2014 Arévalo et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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