AIM: Pemetrexed is a commonly used chemotherapeutic agent for lung adenocarcinoma patients. We investigated the impact of the genetic polymorphisms on the therapeutic efficacy of pemetrexed in lung adenocarcinoma patients. MATERIALS & METHODS: We performed genotying of 51 polymorphisms of 13 genes in 243 lung adenocarcinoma patients treated with pemetrexed as a single agent for second or more line of therapy. RESULTS: Total 12 polymorphisms in six genes were showed statistical significances in univariate analysis. After a false-discovery rate correction, the associations between GGH rs16930092 (p = 0.034) and rs10464903 (p = 0.034), and progression-free survival (PFS) were still conserved. Two polymorphisms in ATIC and GGH genes were associated with therapeutic efficacy in multivariate analysis: ATIC rs12995526 for tumor response (p = 0.014) and for overall survival (p = 0.006), and GGH rs16930092 (p = 0.009) for PFS. CONCLUSION: This study shows that polymorphisms on genes related to the metabolic pathway of pemetrexed, especially, ATIC and GGH genes, would have a therapeutic implication in pemetrexed-treated patients with lung adenocarcinoma. Original submitted 10 May 2013; Revision submitted 27 June 2014.
AIM: Pemetrexed is a commonly used chemotherapeutic agent for lung adenocarcinomapatients. We investigated the impact of the genetic polymorphisms on the therapeutic efficacy of pemetrexed in lung adenocarcinomapatients. MATERIALS & METHODS: We performed genotying of 51 polymorphisms of 13 genes in 243 lung adenocarcinomapatients treated with pemetrexed as a single agent for second or more line of therapy. RESULTS: Total 12 polymorphisms in six genes were showed statistical significances in univariate analysis. After a false-discovery rate correction, the associations between GGHrs16930092 (p = 0.034) and rs10464903 (p = 0.034), and progression-free survival (PFS) were still conserved. Two polymorphisms in ATIC and GGH genes were associated with therapeutic efficacy in multivariate analysis: ATICrs12995526 for tumor response (p = 0.014) and for overall survival (p = 0.006), and GGHrs16930092 (p = 0.009) for PFS. CONCLUSION: This study shows that polymorphisms on genes related to the metabolic pathway of pemetrexed, especially, ATIC and GGH genes, would have a therapeutic implication in pemetrexed-treated patients with lung adenocarcinoma. Original submitted 10 May 2013; Revision submitted 27 June 2014.