title: Polymorphisms in thymidylate synthase and reduced folate carrier (SLC19A1) genes predict survival outcome in advanced non-small cell lung cancer patients treated with pemetrexed-based chemotherapy.
abstract: The aim of this study was to evaluate the association between thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR) and reduced folate carrier (SLC19A1)gene polymorphisms and the treatment efficacy of pemetrexed-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Advanced NSCLC patients received pemetrexed and cisplatin every three weeks. Polymorphisms in theTS,MTHFRandSLC19A1genes were detected in peripheral blood samples using DNA sequencing and Taqman PCR. An analysis of gene polymorphisms was performed with respect to the progression-free survival (PFS), response rate (RR) and overall survival (OS) of patients treated with pemetrexed. The median PFS times for patients with theTS2R/2R, 2R/3C or 3C/3C genotypes were significantly longer than those of patients with the 2R/3G, 3C/3G or 3G/3G genotypes (P=0.036). Patients with theSLC19A1CC genotype had a significantly longer median OS compared with individuals with the homozygous and heterozygous genotypes (12.2 vs. 8.9 and 7.3 months, respectively; P=0.022). The PFS and OS did not differ for the three genotypes ofMTHFRassessed. The RR was higher in patients with theTS2R/2R, 2R/3C or 3C/3C genotypes than in the other groups (P=0.044). The polymorphisms of the 5'-UTR of theTSgene and exon 6 (2522) C/T of theSLC19A1gene predict the survival of advanced NSCLC patients treated with pemetrexed. However, a large scale clinical trial is required to validate these findings.
authors.affiliation: Department of Medical Oncology, The Second People's Hospital of Lianyungang (Lianyungang Hospital Affiliated to Bengbu Medical College), Jiangsu 222000, P.R. China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.forename: Xin-Jian
authors.initials: XJ
authors.lastname: Fang
authors.forename: Hong-Ling
authors.initials: HL
authors.lastname: Ye
authors.forename: Ming-Huan
authors.initials: MH
authors.lastname: Liu
authors.forename: Yan-Wen
authors.initials: YW
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jin-Yu
authors.initials: JY
authors.lastname: Zhang
authors.forename: Chun-Luan
authors.initials: CL
authors.lastname: Yuan
authors.forename: Qiu-Yun
authors.initials: QY
authors.lastname: Zhang
keywords: SLC19A1; advanced non-small cell lung cancer; methylenetetrahydrofolate reductase; pemetrexed; single nucleotide polymorphism; thymidylate synthase