Gene-diet interactions in gastric cancer risk: A systematic review

Table 1 Interactive effect between DNA synthesis and repair-related genetic polymorphisms and diet on gastric cancer risk

Ref.	No. case/control	Gene	Diet/nutrient	Outcome
	(control)	(polymorphism)		Gene	Diet/nutrient	Interaction
Takezaki et al[24], 2002, China	101/198 (Population)	hOGG1 (Ser326Cys)	Meat, soybean, vegetable, garlic, tea, alcohol	No assoc	Pickled vegetable (freq. vs non-freq): OR = 2.53 (1.52-4.21)	The positive assoc between pickled vegetable (P interaction = 0.093) or meat (P interaction = 0.083) and GC risk was stronger in Cys/Cys carriers than in Ser carriers; a frequent alcohol consumption (≥ 2 times/wk) increased GC risk in Cys/Cys carriers (P interaction = 0.086)
Stolzenberg-Solomon et al[18], 2003, China	90/398 (Population)	MTHFR (C677T, A1298C)	Alcohol	No assoc	Unknown	Alcohol drinkers increased GC risk among those with MTHFT 677TT carriers (P interaction = 0.03)
		MTRR (A66G)
Tsukino et al[23], 2004, Japan	142/271 (Hospital)	hOGG1 (Ser326Cys)	Salt, fruit, vegetable, Vt C, β-carotene	No assoc	Unknown	The positive assoc between salt and GC risk was observed only in Cys allele carriers (P interaction = 0.01); the protective effect of cruciferous vegetable on GC risk was stronger among Ser/Ser genotype carriers (P interaction = 0.053)
Huang et al[25], 2005, Poland	281/390 (Population)	XRCC (Arg399Gln) XPD (Lys751Gln) MGMT (Ile143Val, Leu84Phe) XRCC3 (Thr241Met)	Fruit/vegetable	No assoc	Fruit (low vs high): OR = 2.2 (1.3-3.6)	The positive assoc between low fruit or vegetable intake was modified by selected polymorphisms in XRCC1, XPD, MGMT (P interaction = 0.1-0.2)
Nan et al[26], 2005, South Korea	110/220 (Hospital)	hMLH1 promoter	Cereal, potato, fruit, vegetable, mushroom, butter/cheese/margarine, protein, Vt C, P, K, Zn, Ca, alcohol	Unknown	Unknown	High vegetables increased GC risk and high potato intake decreased GC risk among cases with hMLH1 promoter hypermethylation; high intake of protein, P, K, Zn, Vt C, and Ca was associated with higher GC risk without hypermethylation of the hMLH1 gene promoter; high alcohol consumption was associated with a higher GC risk among those with hypermethylation of the hMLH1 gene promoter
Graziano et al[19], 2006, Italy	162/164 (Population)	MTHFR (C677T)	Alcohol	677TT vs CC: OR = 2.95 (1.57-5.55)	Unknown	Alcohol drinking modified the association between MTHFR C677T and GC risk (P interaction = 0.09)
Lacasaña-Navarro et al[21], 2006, Mexico	201/427 (Hospital)	MTHFR (C677T)	Folate, alcohol	677TT vs CC: OR = 1.62 (1.00-2.59)	No assoc	No interaction
Boccia et al[16], 2007, Italy	102/254 (Hospital)	MTHFR (C677T, A1298C)	Fruit, vegetable, alcohol	677TT vs CC for diffuse GC: OR = 2.92 (1.19-5.58)	Alcohol (high vs low): OR = 3.74 (1.13-12.45)	Low fruit/vegetable consumers increased GC risk among individuals with 677TT genotype
Mu et al[17], 2007, China	206/415 (Population)	MTHFR (C677T, A1298C)	Fruit, vegetable	677TT vs CC: OR = 2.80 (1.41-5.56)	No assoc	MTHFR 677TT genotype showed a stronger positive association among low fruit/vegetable intake subjects compared with high intake groups
Zhang et al[11], 2007, Poland	305/427 (Population)	MTHFR (2 SNPs) MTR (1 SNP) MTRR (7 SNPs)	Folate	No assoc	No assoc	No interaction
Galván Portillo et al[14], 2009, Mexico	248/478 (Population)	MTHFR (C677T)	Folate, choline, Vt B6, Vt B12, methionine	677TT vs C allele: OR = 0.23 (0.06-0.84)	Folate (P = 0.001)	Among individuals with MTHFR 677TT genotype, low folate intake increased, but high folate intake decreased diffuse GC risk (P interaction = 0.055)
Duan et al[29], 2012, China	400/400 for rs751402; 403/403 for rs2296147(Population)	ERCC5 (rs751402, rs2296147)	Alcohol	rs751402(AA vs GG):OR = 1.99 (1.20-3.31)rs2296147(CC vs TT): OR = 2.17 (1.04-4.54)	Unknown	Alcohol drinking substantially increased GC risk for subjects carrying rs2296147 CC homozygous variants, but their interaction was not statistically significant
Gao et al[15], 2013, China	264/535 (Population)	MTHFR (C677T)	Folate	677TT vs CC: OR = 2.08 (1.28-3.66)	Folate (high vs low): OR = 0.54 (0.34-0.83)	MTHFR 677TT carriers increased GC risk among subjects with low folate intake (P interaction = 0.005）

ERCC5: Excision repair cross-complementing group 5; hOGG1: Human 8-oxoguanine DNA glycosylase 1; hMLH1: Human mutL homolog 1; MTHFR: Methylenetetrahydrofolate reductase; MGMT: O-6-methylguanine-DNA methyltransferase; MTR: 5-methyltetrahydrofolate-homocysteine methyltransferase; MTRR: 5-methyltetrahydrofolate-homocysteine methyltransferase reductase; XPD: Xeroderma pigmentosum D; XRCC: X-ray repair complementing defective repair in Chinese hamster cells; Freq: Frequent; GC: Gastric cancer; No assoc: No association; OR: Odds ratio; Vt: Vitamin; P: Phosphorous; K: Potassium; Zn: Zinc; Ca: Calcium.