Abstract
e19014 Background: Pemetrexed has been approved for first- and second-line treatment in patients with non-small cell lung cancer (NSCLC). Two studies have confirmed the role of polymorphisms (SNPs) in reduced folate carrier (SLC19A1) is related with the survival differences in pemetrexed-treated NSCLC in Caucasian population. Considering different genetic backgrounds in different populations, our study was aimed to identify candidate SNPs for pemetrexed-treated NSCLC in Chinese Han population. Methods: Fifty-seven patients with previously treated NSCLC received pemetrexed-based third-line treatment from Shanghai Chest Hospital from Nov 2006 to Jul 2011. Four genes, SLC19A1, gamma-glutamyl hydrolase (GGH), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase (MTR), responsible for pemetrexed transport and activation were evaluated. The five SNPs (rs4819128, rs914232, rs4818789, rs3788189, rs1051298) in SLC19A1, two SNPs (rs3780130, rs3780126) in GGH, two SNPs (rs1801133, rs180131) in MTHER, and one SNP (rs1805087) in MTR were selected based on the HapMap Chinese Han databases. All SNP genotyping was performed by TaqMan PCR using the ABI Prism 7900HT Sequence Detection System. Kaplan-Meier cumulative probability and Cox multivariate analyses were used to evaluate the relationship between genetic variations with survival outcome. Results: Fifty-seven patients received a median of three cycles (range, 1-16 cycles) of pemetrexed-based treatment. Median overall survival (OS) and progression-free survival (PFS) times were 23.0 and 3.2 months, respectively. Patients with AA/AG genotype of SLC19A1 rs1051298 had the better PFS and OS compared with GG genotype (5.5m vs 1.9m for PFS, P=0.047; 45.5m vs 17m for OS, P=0.001). The TT/TA genotype of novel GGH rs3780130 was correlated with better PFS compared with AA genotype (5.8m vs 2.5m, P=0.029). Conclusions: This study in Chinese Han NSCLC patients identified the unique result that novel TT/TA genotype of GGH rs3780130 was related with better PFS for pemetrexed-based treatment. Meanwhile, we obtained the same result with that in Caucasian study, AA/AG genotype of SLC19A1 rs1051298 was related with better PFS and OS.
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