Genetic polymorphisms in folate-metabolizing genes associated with gastric cancer prognosis in northwest China subjects

Lijuan Yuan; Ziyu Liu; Gang Wei; Ping Yang; Xi E Hu; Falin Qu; Jianguo Lu; Xianli He; Guoqiang Bao

doi:10.7150/jca.46978

Genetic polymorphisms in folate-metabolizing genes associated with gastric cancer prognosis in northwest China subjects

J Cancer. 2020 Sep 13;11(21):6413-6420. doi: 10.7150/jca.46978. eCollection 2020.

Authors

Lijuan Yuan¹, Ziyu Liu², Gang Wei¹, Ping Yang¹, Xi E Hu¹, Falin Qu¹, Jianguo Lu¹, Xianli He¹, Guoqiang Bao¹

Affiliations

¹ Department of General Surgery, Tangdu Hospital, The Air Force Military Medical University, Xi'an, 710038, China.
² Department of Microbiology, The Air Force Military Medical University, Xi'an, 710032, China.

Abstract

Influence of folate metabolism has long been studied in cancer and copies evidences have suggested that the key genes involved were correlated with GC risk and prognosis. However, their genetically association and contribution for GC prognosis are still elusive. To evaluate the effect of folate metabolism related genes polymorphisms on the prognosis of gastric cancer (GC), the genotype of seven single nucleotide polymorphisms (SNPs) of three genes were selected and genotyped in a cohort of 664 GC patients, including genes of Methylenetetrahydrofolate reductase (MTHFR), Methionine synthase reductase (MTRR), and Methionine synthase (MTR). Kaplan-Meier Curve, long-rank tests and multivariate Cox proportional hazard model were used for prognosis analysis. The results demonstrated that TT or CT/TT genotypes of SNP rs1532268 in MTRR gene coding region are significantly associated with a poorer overall survival (OS) when compared with CC genotype (HR=2.340, 95% CI: 1.240-4.414, p=0.009; or HR=1.502, 95% CI: 1.083-2.085, p=0.015, respectively). Furthermore, comparing to that of the CC genotype, the detrimental effect of rs1532268 TT genotype was also evident in the special subgroups of GC patients, especially in patients with BMI<24 and H. pylori infection. Moreover, significant association between increased relapse and TT genotype of rs1532268 was also observed in patients who are females, BMI<24 and without chemotherapy. In addition, the joint analysis demonstrated that integration of rs1532268 genotypes and BMI, H. pylori infection status, clinical stage and tumor site may significantly improve the predictive abilities for predicting OS of GC patients. In conclusion, it suggested that the MTRR rs1532268 polymorphism is significantly associated with clinical outcomes of GC patients, especially in those with lower BMI (BMI<24) or positive H. pylori infection status, which warrants further validation. And the polymorphism of MTRR rs1532268 may be a potential prognostic factor for GC patients.

Keywords: MTHFR; MTR; MTRR; folate metabolism; gastric cancer prognosis; polymorphism.