Polymorphism in One-carbon Metabolism Pathway Affects Survival of Gastric Cance
PUBLISHED: 2015-11-27  325 total views, 1 today

Tingting Zhao1, Dongying Gu2, Jinfei Chen2, Zhi Xu2, Xinying Huo2Lili Chen2, Chun Wang2, Yongfei Tang3, Peng Wu2, Jason He4Weida Gong5, Mingliang He6

1Department of Oncology,Nanjing First Hospital, Nanjing Medical University, 2Nanjing MedicalUniversity, Nanjing First Hospital, 3Department of Surgery,Yixing People's Hospital, 4Berkeley, University ofCalifornia, 5Department of Surgery,Yixing Cancer Hospital, 6Department of BilmedicalScience, City University of HongKong


Objective:Although it has been shown thatpolymorphisms in one-carbon metabolism (OCM) pathway are associated withgastric cancer (GC), their interactions and contributions for patients'survival are elusive. In this study, we investigated the effects ofpolymorphisms and their interactions on the survival of GC patients, includinggenes of Methylenetetrahydrofolatereductase (MTHFR 677C>T,1298A>C), Methioninesynthase reductase (MTRR66A>G), Methionine synthase(MTR 2756A>G), and Thymidylate synthase (TS 3'-UTR ins6 > del6, 5'-UTR 2R>3R).Method: We recruited 919 GC patients from 1998 to 2006. The Kaplan–Meierplots, Cox regression analyses and the log-rank tests were carried out in thisstudy. Result: MTHFR1298CCgenotype showed protective effect (HR=0.444, 95% CI=0.210-0.940). MTRR 66 GA+GG genotypes decreased therisk of death (HR=0.793, 95% CI=0.651-0.967) in general, and in subgroups withmore pronounced diffuse type, greater depth of invasion (T2/T3/T4), higherlevel lymph node metastasis (N1/N2/N3), advanced TNM stages (II/III level) and5-Fu treatment. However, the improved survival disappeared when GC patientssimultaneously had MTR 2756 GA+GG genotypes (HR=1.063, 95% CI=0.750-1.507). Although MTRR 66GA genotype was not associated with the survival of GCpatients, patients with simultaneous MTRR66GA and MTR 2756AA genotypes exhibitedsignificant risk reduction of death (HR=0.773, 95% CI=0.609-0.981). MTHFR 1298 CA + CC combined with TS 5-UTR 2R3R + 3R3Rgenotypes (HR=0.536, 95% CI=0.315-0.913) also increased patient survival rates.Conclusion: Our results suggest that the MTRR 66A>Gand MTHFR 1298A>C polymorphisms may beuseful prognostic biomarkers for GC patients.


Key Words: one-carbonmetabolism (OCM)  single nucleotide polymorphisms

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