Table 3.

Effect of the polymorphisms on gastric cancer risk.

Study Type	Number of Participants	Ethnicity	SNP	Risk Association	References
Case-control	70 GC and 61 controls	Turkish	C677T A1298C	The AC genotype of the A1298C polymorphism is a risk factor for GC. The TT genotype of C677T was not at a higher risk than the CC genotype.	[135]
Case-control	307 GC and 560 controls	Chinese	C677T	TT genotype associated with a decreased risk for GC	[136]
Case-control	107 GC and 220 controls	Chinese	C677T	MTHFR variant genotypes + smoking and drink habits are associated with a higher risk for GC	[137]
Meta-analysis	5757 GC and 8501 controls	Asian and Caucasian	C677T	Significant association was found between GC and the MTHFR C677T polymorphism. Elevated risk of GC in Asian individuals carrying the MTHFR C677T polymorphism, but not in Caucasian populations	[138]
Meta-analysis	1584 GC and 2785 controls	Asian and Caucasian	C677T A1298C	MTHFR C677T and A1298C polymorphisms, respectively, contribute to the susceptibility of GC. In East Asian populations with C677T, the association was significant but not in Caucasian populations. The A1298C polymorphism was associated with GCA in East Asian populations.	[139]
Case-control	790 GC and 202 controls	Italian	C677T A1298C	Increased risk of GC for the C677T variant (homozygous TT), but no effect of the A1298C polymorphism.	[140]
Meta-analysis	2727	Asian, Caucasian and Mixed	C677T	MTHFR C677T was associated with GC	[141]
Meta-analysis	6572 GC and 9584 controls	Asian, Caucasian and Mixed	C677T A1298C	C677T was related to a significantly increased risk for GC. No correlation was found with A1298C. C677T, but not A1298C, was associated with an increased risk of GC in Asian and Caucasian populations	[142]
Meta-analysis	4070/6462 cases/controls for C677T and 1923/3561 cases/controls for A1298C polymorphism	Eastern and Western	C677T A1298C	No significant association was found in the CC genotype of A1298C. The C677T allele T was associated with an increased risk of GC. Subgroup analyses revealed an increased risk for Asian populations but not for Caucasian populations	[143]
Case-control	76 GC and 91 controls	Turkish	C677T	CT heterozygotes had a lower susceptibility to GC	[144]
Meta-analysis	1718	Asian, European and Mixed	C677T	TT was related more to hematologic toxicity than the CC or CT genotype	[147]
Multicenter, single-arm, phase 2 study	60	Dutch	C677T	The TT genotype was related to inferior progression-free survival and OS	[150]
Retrospective comparative exploratory study	218	German	C677T A1298C	A1298C was an independent prognostic factor associated with a poor prognosis in neoadjuvantly treated GC patients	[151]
Single-center, cross sectional observational trial	128	Chinese	C677T	The TT genotype showed an increased risk of moderate-to-severe precancerous gastric lesions	[152]
Case-control study	450 GC and 780 controls	Iranian	C677T	MTHFR C677T carriers who were also positive for H. pylori, showed an increased risk for GC	[153]
Case-control	58 GC patients with H. pylori infection and 94 non-infected patients	Chinese	C677T	TT genotype was considered a susceptibility factor of H. pylori infection.	[154]