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

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.

MTRR rs1532268 polymorphism and gastric cancer risk: evidence from a meta-analysis

“…Researchers have indicated that high riboflavin consumption significantly decreases the risk of GC in TC and TT carriers compared with that in CC carriers, 8 , 21 and it was reported that TT or CT/TT genotypes were significantly associated with poorer overall survival. 10 This provided a clue that riboflavin consumption may improve patient survival.…”

“… 9 Among these polymorphisms, CT/TT or TT genotypes of the single nucleotide polymorphism rs1532268 in the MTRR gene coding region are significantly associated with a poorer overall survival compared with the CC genotype. 10 Several studies have evaluated the relationship between the risk of GC and the rs1532268 polyporphism, 8 , 9 , 11 – 13 but the results have been inconsistent. Thus, we conducted this meta-analysis to assess the effect of the rs1532268 polymorphism on GC susceptibility.…”

The combination of methylenehydrofolate reductase C677T polymorphism screening and gastrointestinal tumor markers detection may be an early screening method for gastrointestinal cancer related to helicobacter pylori infection

“… 38 Although many studies have shown that MTHFR C677T polymorphism was associated with gastrointestinal cancer, the specific relationship was not clear. 18 , 38 , 39 We speculated that the specificity of MTFHR C677T polymorphism for gastrointestinal cancer during H.pylori infection might be related to the site of cancer origin. 19 , 40 The previous studies have reported that there was association between MTHFR C677T polymorphism and gastric cancer in Chongqing, and CT and TT genotypes were protective factors for gastric cardia cancer, and TT genotype was a risk factor for gastric body cancer.…”

The Role of Methionine Restriction in Gastric Cancer: A Summary of Mechanisms and a Discussion on Tumor Heterogeneity

“…On the other hand, the overexpression of Metase significantly promotes apoptosis and autophagy, thereby inhibiting gastric cancer [40,45,46]. Additionally, Met can exert an impact on the development of gastric cancer by influencing the survival of Helicobacter pylori [47][48][49][50]. It has been shown that Met enhances the efficacy of the chemotherapeutic drugs 5-fluorouracil and Cisplatin [47,[51][52][53].…”

“…Additionally, Met can exert an impact on the development of gastric cancer by influencing the survival of Helicobacter pylori [47][48][49][50]. It has been shown that Met enhances the efficacy of the chemotherapeutic drugs 5-fluorouracil and Cisplatin [47,[51][52][53]. The objective of this review is to analyze the role and mechanism of Met in the development of gastric cancer and to consider its potential implications in the treatment of gastric cancer.…”