Susceptibility of Genetic Variations in Methylation Pathway to Gastric Cancer

Figures & data

Table 1 Associations Between DNMT1/DNMT3A/DNMT3B and MTHFR genetic variations and Gastric Cancer Risk

Genotype	Cases, n(%)	Controls, n(%)	OR (95% CI)	AOR (95% CI)^a	p-value
DNMT1 rs16999593
TT	324(66.12)	318(65.16)	Reference	Reference
CT	148(30.20)	148(30.33)	0.98(0.75–1.29)	0.93(0.70–1.23)	0.61
CC	18 (3.67)	22(4.51)	0.80(0.42–1.53)	0.84(0.44–1.60)	0.59
CT/CC	166(33.87)	170(34.84)	0.96(0.74–1.25)	0.92(0.70–1.20)	0.53
DNMT1 rs10420321
AA	167(34.08)	161(32.99)	Reference	Reference
AG	223(45.51)	221(45.29)	0.97(0.73–1.29)	0.94(0.70–1.26)	0.69
GG	100(20.41)	106(21.72)	0.91(0.64–1.29)	0.89(0.62–1.27)	0.52
AG/GG	323(65.92)	327(67.01)	0.95(0.73–1.24)	0.93(0.71–1.21)	0.58
DNMT1 rs2228612
TT	199(40.7)	165(33.81)	Reference	Reference
CT	196(40.08)	225(46.11)	0.72(0.55–0.96)	0.70(0.53–0.94)	0.02
CC	94(19.22)	98(20.08)	0.80(0.56–1.13)	0.80(0.56–1.14)	0.21
CT/CC	290(59.30)	323(66.19)	0.74(0.57–0.97)	0.73(0.56–0.96)	0.02
DNMT1 rs7560488
TT	328(66.94)	319(65.37)	Reference	Reference
TC	148(30.20)	152(31.15)	0.95(0.72–1.25)	0.98(0.74–1.29)	0.86
CC	14(2.86)	17(3.48)	0.80(0.39–1.65)	0.78 (0.37–1.62)	0.50
TC/CC	162(33.06)	169(34.63)	0.93(0.72–1.22)	0.95(0.73–1.25)	0.72
DNMT3A rs13420827
CC	323(65.92)	307(62.91)	Reference	Reference
GC	150(30.61)	163(33.40)	0.88(0.67–1.15)	0.87(0.66–1.15)	0.34
GG	17(3.47)	18(3.69)	0.90(0.45–1.77)	0.88(0.44–1.75)	0.71
GC/GG	167(34.08)	181(37.09)	0.88(0.68–1.14)	0.87(0.67–1.13)	0.30
DNMT3A rs1550117
GG	321(65.51)	305(62.50)	Reference	Reference
AG	152(31.02)	164(33.61)	0.88(0.67–1.15)	0.87(0.66–1.15)	0.33
AA	17(3.47)	19(3.89)	0.85(0.43–1.67)	0.85(0.43–1.67)	0.63
AG/AA	169(34.49)	183(37.5)	0.88(0.68–1.14)	0.87(0.67–1.13)	0.29
DNMT3B rs1569686
TT	423(86.33)	416(85.25)	Reference	Reference
GT	61(12.45)	70(14.34)	0.86(0.59–1.24)	0.85(0.58–1.24)	0.40
GG	6(1.22)	2(0.41)	2.95(0.59–14.70)	3.33(0.66–16.73)	0.14
GT/GG	67(13.67)	72(14.75)	0.92(0.64–1.31)	0.92(0.64–1.32)	0.64
MTHFR rs1476413
CC	324(66.12)	329(67.42)	Reference	Reference
CT	152(31.02)	146(29.92)	1.06(0.80–1.39)	1.03(0.78–1.37)	0.81
TT	14(2.86)	13(2.66)	1.09(0.51–2.36)	1.17(0.53–2.56)	0.70
CT/TT	166(33.88)	159(32.58)	1.06(0.81–1.38)	1.05(0.80–1.37)	0.74
MTHFR rs1801131
TT	327(66.73)	333(68.24)	Reference	Reference
GT	149(30.41)	142(29.10)	1.07(0.81–1.41)	1.05(0.79–1.39)	0.75
GG	14(2.86)	13(2.66)	1.10(0.51–2.37)	1.17(0.54–2.57)	0.69
GT/GG	163(33.27)	155(31.76)	1.07(0.82–1.40)	1.06(0.81–1.39)	0.68

Note: ^aAdjusted by age, smoking, drinking, and H. pylori infection status.

Abbreviation: AOR, adjusted OR.

Table 2 Subgroup Analysis of rs2228612 to Gastric Cancer Risk

Variables	rs2228612 (Cases/Controls)		AOR (95% CI)^a	p-value
	TT	CT/CC
Age
≤64	99/73	131/154	0.61(0.41–0.90)	0.01
>64	100/92	159/169	0.87(0.61–1.25)	0.46
Gender
Male	148/121	210/237	0.72(0.53–0.98)	0.03
Female	51/44	80/86	0.79(0.47–1.32)	0.37
H. pylori infection
Positive	111/86	157/152	0.81(0.56–1.17)	0.26
Negative	88/79	133/171	0.67(0.45–0.98)	0.04
Differentiation
Low	109/165	161/323	0.73(0.54–1.00)	0.05
Median to high	84/165	124/323	0.74(0.53–1.05)	0.09
Clinical stage
I–II	61/165	96/323	0.84(0.57–1.24)	0.38
III–IV	138/165	194/323	0.69(0.51–0.92)	0.01
Tumor site
Cardia	56/165	84/323	0.75(0.50–1.10)	0.14
Non-cardia	143/165	206/323	0.72(0.54–0.97)	0.03

Note: ^aAdjusted by age, smoking, drinking, and H. pylori infection status.

Abbreviation: AOR, adjusted OR.

Table 3 Analysis of Associations Between Genetic Variations and Clinical Outcomes

Genotype	Cases, n	Death, n (%)	Log-Rank p-value	HR
rs16999593
TT	313	207 (66.1)		Reference
CT/CC	164	108 (65.9)	0.923	0.989 (0.783–1.248)
rs10420321
AA	160	104 (65)		Reference
AG/GG	317	211 (66.6)	0.950	1.007 (0.797–1.274)
rs2228612
TT	191	121 (63.4)		Reference
CT/CC	285	194 (68.1)	0.587	1.065 (0.849–1.336)
rs7560488
TT	321	210 (65.4)		Reference
CT/CC	156	105 (67.3)	0.514	1.081 (0.855–1.367)
rs13420827
CC	314	206 (65.6)		Reference
GC/GG	163	109 (66.9)	0.654	1.054 (0.836–1.330)
rs1550117
GG	313	200 (63.9)		Reference
AG/AA	164	115 (70.1)	0.392	1.105 (0.879–1.391)
rs1569686
TT	411	271 (65.9)		Reference
GT/GG	66	44 (66.7)	0.947	1.011 (0.735–1.390)
rs1476413
CC	318	216 (67.9)		Reference
CT/TT	159	99 (62.3)	0.105	0.821 (0.647–1.042)
rs1801131
TT	321	219 (68.2)		Reference
GT/GG	156	96 (61.6)	0.064	0.797 (0.627–1.013)