Case Control Study
Copyright ©The Author(s) 2018.
World J Gastroenterol. Feb 7, 2018; 24(5): 602-612
Published online Feb 7, 2018. doi: 10.3748/wjg.v24.i5.602
Table 1 Baseline characteristics of the subjects n (%)
VariableAG vs CON
GC vs CON
CONAGCONGC
n = 620n = 634n = 535n = 450
GenderP = 0.492P = 0.588
Male362 (58.4)358 (56.5)363 (67.9)298 (66.2)
Female258 (41.6)276 (43.5)172 (32.1)152 (33.8)
AgeP = 0.845P = 0.235
mean ± SD54.7 ± 9.154.8 ± 9.055.6 ± 9.256.3 ± 10.1
Median54555657
Range17-8516-8217-8526-84
H. pylori infection statusP < 0.001P < 0.001
Positive168 (27.1)377 (59.5)143 (26.7)223 (49.6)
Negative452 (72.9)257 (40.5)392 (73.3)227 (50.4)
Table 2 Impact of two-way interactions between ERCC5 polymorphisms and GSTP1 rs1695 on risk of atrophic gastritis and gastric cancer1
GeneGenotypeNumber of participantsGSTP1 rs1695
AAGA + GGAA + GAGG
AG vs CON
(n = 634 vs 620 )
ERCC5 rs1047768TTNo. of cases/controls231/200124/116338/30717/9
OR (95%CI)1 (Ref.)0.93 (0.68-1.27)1 (Ref.)1.72 (0.75-3.91)
TC + CCNo. of cases/controls177/188102/116270/2899/15
OR (95%CI)0.82 (0.62-1.08)0.76 (0.55-1.06)0.85 (0.68-1.07)0.55 (0.24-1.26)
Pinteraction = 0.317Pinteraction = 0.683
Interaction index = 0.88Interaction index = 1.13
TT + TCNo. of cases/controls376/345207/214559/53824/21
OR (95%CI)1 (Ref.)0.89 (0.70-1.13)1 (Ref.)1.10 (0.61-2.00)
CCNo. of cases/controls32/4319/1849/582/3
OR (95%CI)0.68 (0.42-1.10)0.97 (0.50-1.87)0.81 (0.55-1.21)0.64 (0.11-3.86)
Pinteraction = 0.296Pinteraction = 0.531
Interaction index = 0.88Interaction index = 0.88
ERCC5 rs2094258GGNo. of cases/controls132/16293/84214/23411/12
OR (95%CI)1 (Ref.)1.36 (0.94-1.98)1 (Ref.)1.00 (0.43-2.32)
GA + AANo. of cases/controls276/226133/148394/36215/12
OR (95%CI)1.50 (1.12-2.00)1.10 (0.79-1.53)1.19 (0.94-1.50)1.37 (0.63-2.99)
Pinteraction = 0.008Pinteraction = 0.842
Interaction index = 0.51Interaction index = 1.13
GG + GANo. of cases/controls337/328195/204508/51024/22
OR (95%CI)1 (Ref.)0.93 (0.73-1.19)1 (Ref.)1.10 (0.61-1.98)
AANo. of cases/controls71/6031/28100/862/2
OR (95%CI)1.15 (0.79-1.68)1.08 (0.63-1.84)1.17 (0.85-1.60)1.00 (0.14-7.15)
Pinteraction = 0.594Pinteraction = 0.620
Interaction index = 0.83Interaction index = 0.58
ERCC5 rs2228959CCNo. of cases/controls371/346198/215548/53921/22
OR (95%CI)1 (Ref.)0.86 (0.67-1.09)1 (Ref.)0.94 (0.51-1.73)
CA + AANo. of cases/controls37/4228/1760/575/2
OR (95%CI)0.82 (0.52-1.31)1.54 (0.83-2.86)1.04 (0.71-1.52)2.46 (0.48-12.73)
Pinteraction = 0.103Pinteraction = 0.435
Interaction index = 2.00Interaction index = 2.11
CC + CANo. of cases/controls408/383224/231606/59026/24
OR (95%CI)1 (Ref.)0.91 (0.72-1.15)1 (Ref.)1.06 (0.60-1.86)
AANo. of cases/controls0/52/12/60/0
OR (95%CI)NA1.88 (0.17-20.79)0.32 (0.07-1.61)NA
Pinteraction = NAPinteraction = 0.720
Interaction index = NAInteraction index = 1.12
ERCC5 rs4150291AANo. of cases/controls347/332193/205517/51623/21
OR (95%CI)1 (Ref.)0.90 (0.70-1.15)1 (Ref.)1.09 (0.60-2.00)
AT + TTNo. of cases/controls61/5633/2791/803/3
OR (95%CI)1.04 (0.70-1.54)1.17 (0.69-1.99)1.14 (0.82-1.57)1.00 (0.20-4.97)
Pinteraction = 0.667Pinteraction = 0.679
Interaction index = 1.17Interaction index = 0.68
AA + ATNo. of cases/controls406/382225/232605/59026/24
OR (95%CI)1 (Ref.)0.91 (0.73-1.15)1 (Ref.)1.06 (0.60-1.86)
TTNo. of cases/controls2/61/03/60/0
OR (95%CI)0.31 (0.06-1.56)NA0.49 (0.12-1.96)NA
Pinteraction = NAPinteraction = 0.703
Interaction index = NAInteraction index = 1.12
ERCC5 rs4150383GGNo. of cases/controls365/344197/202539/52623/20
OR (95%CI)1 (Ref.)0.92 (0.72-1.18)1 (Ref.)1.12 (0.61-2.07)
GA + AANo. of cases/controls43/4429/3069/703/4
OR (95%CI)0.92 (0.59-1.44)0.91 (0.54-1.55)0.96 (0.68-1.37)0.73 (0.16-3.29)
Pinteraction = 0.720Pinteraction = 0.894
Interaction index = 1.15Interaction index = 1.12
GG + GANo. of cases/controls406/387226/231606/59426/24
OR (95%CI)1 (Ref.)0.93 (0.74-1.17)1 (Ref.)1.06 (0.60-1.87)
AANo. of cases/controls2/10/12/20/0
OR (95%CI)1.91 (0.17-21.11)NA0.98 (0.14-6.98)NA
Pinteraction = NAPinteraction = 0.695
interaction index = NAinteraction index = 1.13
ERCC5 rs751402CCNo. of cases/controls191/17397/104281/2667/11
OR (95%CI)1 (Ref.)0.85 (0.60-1.19)1 (Ref.)0.60 (0.23-1.58)
CT + TTNo. of cases/ controls203/198124/118308/30319/13
OR (95%CI)0.93 (0.70-1.23)0.95 (0.69-1.32)0.96 (0.76-1.21)1.38 (0.67-2.86)
Pinteraction = 0.196Pinteraction = 0.109
Interaction index = 1.39Interaction index = 2.84
CC + CTNo. of cases/ controls355/324193/196526/50022/20
OR (95%CI)1 (Ref.)0.90 (0.70-1.15)1 (Ref.)1.05 (0.56-1.94)
TTNo. of cases/ controls39/4728/2663/694/4
OR (95%CI)0.76 (0.48-1.19)0.98 (0.56-1.71)0.87 (0.60-1.25)0.95 (0.24-3.81)
Pinteraction = 0.488Pinteraction = 0.886
Interaction index = 1.31Interaction index = 1.13
ERCC5 rs873601GGNo. of cases/ controls126/10957/59178/1655/3
OR (95%CI)1 (Ref.)0.84 (0.54-1.30)1 (Ref.)1.55 (0.36-6.57)
GA + AANo. of cases/ controls282/279169/173430/43121/21
OR (95%CI)0.87 (0.64-1.19)0.85 (0.61-1.18)0.93 (0.72-1.19)0.93 (0.49-1.76)
Pinteraction = 0.197Pinteraction = 0.770
Interaction index = 1.44Interaction index = 0.78
GG + GANo. of cases/ controls321/279167/177473/44115/15
OR (95%CI)1 (Ref.)0.82 (0.63-1.07)1 (Ref.)0.93 (0.45-1.93)
AANo. of cases/ controls87/10959/55135/15511/9
OR (95%CI)0.69 (0.50-0.96)0.93 (0.62-1.39)0.81 (0.62-1.06)1.14 (0.47-2.78)
Pinteraction = 0.043Pinteraction = 0.488
Interaction index = 1.79Interaction index = 1.55
GC vs CON
(n = 450 vs 535 )
ERCC5 rs1047768TTNo. of cases/ controls142/16278/105204/25916/8
OR (95%CI)1 (Ref.)0.85 (0.59-1.23)1 (Ref.)2.54 (1.07-6.05)
TC + CCNo. of cases/ controls128/164102/104211/25519/13
OR (95%CI)0.89 (0.65-1.23)1.12 (0.79-1.59)1.05 (0.81-1.36)1.86 (0.89-3.85)
Pinteraction = 0.101Pinteraction = 0.594
interaction index = 1.56interaction index = 0.73
TT + TCNo. of cases/ controls247/292158/193374/46731/18
OR (95%CI)1 (Ref.)0.97 (0.74-1.27)1 (Ref.)2.15 (1.18-3.91)
CCNo. of cases/ controls23/2422/1641/474/3
OR (95%CI)0.80 (0.46-1.39)1.63 (0.84-3.16)1.09 (0.70-1.69)1.67 (0.37-7.49)
Pinteraction = 0.115Pinteraction = 0.640
Interaction index = 2.07Interaction index = 0.66
ERCC5 rs2094258GGNo. of cases/ controls110/13166/77165/19711/11
OR (95%CI)1 (Ref.)1.02 (0.67-1.55)1 (Ref.)1.19 (0.51-2.82)
GA + AANo. of cases/ controls160/195114/132250/31724/10
OR (95%CI)0.98 (0.70-1.36)1.03 (0.72-1.47)0.94 (0.72-1.23)2.87 (1.33-6.17)
Pinteraction = 0.923Pinteraction = 0.134
Interaction index = 0.97Interaction index = 2.47
GG + GANo. of cases/ controls226/275158/185352/44132/19
OR (95%CI)1 (Ref.)1.04 (0.79-1.37)1 (Ref.)2.11 (1.18-3.79)
AANo. of cases/ controls44/5122/2463/733/2
OR (95%CI)1.05 (0.68-1.63)1.12 (0.61-2.04)1.08 (0.75-1.56)1.88 (0.31-11.31)
Pinteraction = 0.801Pinteraction = 0.834
Interaction index = 0.90Interaction index = 0.81
ERCC5 rs2228959CCNo. of cases/ controls247/295164/194380/47031/19
OR (95%CI)1 (Ref.)1.01 (0.77-1.32)1 (Ref.)2.02 (1.12-3.63)
CA + AANo. of cases/ controls23/3116/1535/444/2
OR (95%CI)0.89 (0.50-1.56)1.27 (0.62-2.63)0.98 (0.62-1.57)2.47 (0.45-13.58)
Pinteraction = 0.491Pinteraction = 0.813
Interaction index = 1.40Interaction index = 1.26
CC + CANo. of cases/ controls268/322180/208413/50935/21
OR (95%CI)1 (Ref.)1.04 (0.80-1.35)1 (Ref.)2.05 (1.18-3.58)
AANo. of cases/ controls2/40/12/50/0
OR (95%CI)0.60 (0.11-3.31)NA0.49 (0.10-2.55)NA
Pinteraction = NAPinteraction = NA
Interaction index = NAInteraction index = NA
ERCC5 rs4150291AANo. of cases/ controls222/276143/182338/44027/18
OR (95%CI)1 (Ref.)0.98 (0.74-1.29)1 (Ref.)1.95 (1.06-3.61)
AT + TTNo. of cases/ controls48/5037/2777/748/3
OR (95%CI)1.19 (0.77-1.84)1.70 (1.01-2.89)1.36 (0.96-1.92)3.47 (0.91-13.18)
Pinteraction = 0.385Pinteraction = 0.818
Interaction index = 1.37Interaction index = 1.20
AA + ATNo. of cases/ controls267/321177/209410/50934/21
OR (95%CI)1 (Ref.)1.02 (0.79-1.32)1 (Ref.)2.01 (1.15-3.52)
TTNo. of cases/ controls3/53/05/51/0
OR (95%CI)0.72 (0.17-3.05)NA1.24 (0.36-4.32)NA
Pinteraction = NAPinteraction = NA
Interaction index = NAInteraction index = NA
ERCC5 rs4150383GGNo. of cases/ controls237/288168/180373/45132/17
OR (95%CI)1 (Ref.)1.13 (0.86-1.49)1 (Ref.)2.28 (1.24-4.16)
GA + AANo. of cases/ controls33/3812/2942/633/4
OR (95%CI)1.06 (0.64-1.74)0.50 (0.25-1.01)0.81 (0.53-1.22)0.91 (0.20-4.08)
Pinteraction = 0.060Pinteraction = 0.497
Interaction index = 0.43Interaction index = 0.55
GG + GANo. of cases/ controls270/325180/208415/51235/21
OR (95%CI)1 (Ref.)1.04 (0.81-1.35)1 (Ref.)2.06 (1.18-3.59)
AANo. of cases/ controls0/10/10/20/0
OR (95%CI)NANANANA
Pinteraction = NAPinteraction = NA
Interaction index = 0.90Interaction index = NA
ERCC5 rs751402CCNo. of cases/ controls114/14982/90180/22916/10
OR (95%CI)1 (Ref.)1.19 (0.81-1.75)1 (Ref.)2.04 (0.90-4.59)
CT + TTNo. of cases/ controls142/16189/109212/25919/11
OR (95%CI)1.15 (0.83-1.61)1.07 (0.74-1.55)1.04 (0.80-1.36)2.20(1.02-4.74)
Pinteraction = 0.453Pinteraction = 0.945
Interaction index = 0.81Interaction index = 0.96
CC + CTNo. of cases/ controls225/275156/174348/43233/17
OR (95%CI)1 (Ref.)1.10 (0.83-1.45)1 (Ref.)2.41 (1.32-4.40)
TTNo. of cases/ controls31/3515/2544/562/4
OR (95%CI)1.08 (0.65-1.81)0.73 (0.38-1.42)0.98 (0.64-1.48)0.62 (0.11-3.41)
Pinteraction = 0.409Pinteraction = 0.241
Interaction index = 0.69Interaction index = 0.32
No. of cases/ controls79/9155/53122/14112/3
ERCC5 rs873601GGOR (95%CI)1 (Ref.)1.20 (0.74-1.94)1 (Ref.)4.62 (1.28-16.76)
No. of cases/ controls191/235125/156293/37323/18
GA + AAOR (95%CI)0.94 (0.66-1.34)0.92 (0.63-1.35)0.91 (0.68-1.21)1.48 (0.76-2.87)
Pinteraction = 0.901Pinteraction = 0.217
Interaction index = 0.96Interaction index = 0.40
No. of cases/ controls205/232139/156317/37527/13
GG + GAOR (95%CI)1 (Ref.)1.01 (0.75-1.36)1 (Ref.)2.46 (1.25-4.84)
No. of cases/ controls65/9441/3598/1398/8
AAOR (95%CI)0.78 (0.54-1.13)0.88 (0.56-1.37)0.83(0.62-1.12)1.18 (0.44-3.18)
Pinteraction = 0.477Pinteraction = 0.384
Interaction index = 1.25Interaction index = 0.57
Table 3 Epistatic effect of pair-wise interacting factors on the risk of atrophic gastritis and gastric cancer
Interacted pair-wise SNPsComparisonSubsetAG vs CON
GC vs CON
P valueOR (95%CI)P valueOR (95%CI)
ERCC5 rs2094258 interacted with GSTP1 rs1695ERCC5 rs2094258 GG vs AG + AAGSTP1 rs1695 AA0.0061.523 (1.125-2.062)0.9480.989 (0.704-1.388)
GSTP1 rs1695 GA + GG0.2050.766 (0.508-1.157)0.8200.951 (0.619-1.462)
GSTP1 rs1695 AA vs GA + GGERCC5 rs2094258 GG0.1481.343 (0.901-2.002)0.8081.055 (0.685-1.625)
ERCC5 rs2094258 AG + AA0.0140.678 (0.497-0.926)0.7991.045 (0.745-1.465)
ERCC5 rs873601 interacted with GSTP1 rs1695ERCC5 rs873601 GA + GG vs AAGSTP1 rs1695 AA0.0250.678 (0.483-0.952)0.1480.756 (0.517-1.105)
GSTP1 rs1695 GA + GG0.3801.230 (0.775-1.951)0.8720.961 (0.592-1.560)
GSTP1 rs1695 AA vs GA + GGERCC5 rs873601 GA + GG0.0540.758 (0.571-1.005)0.9550.991 (0.730-1.346)
ERCC5 rs873601 AA0.2261.356 (0.828-2.222)0.5421.183 (0.690-2.027)
Table 4 Cumulative effect of the interacting factors of ERCC5 SNPs-GSTP1 rs1696 on atrophic gastritis risk
No. of interacting genotypesTotal populationH. pylori-negative subpopulationH. pylori-positive subpopulation
Cases/controlsP1 valueOR (95%CI)Cases/controlsP2 valueOR (95%CI)Cases/controlsP2 valueOR (95%CI)
ERCC5 rs2094258-GSTP1 rs1695 on AG risk
0132/1621 (Ref.)57/1151 (Ref.)75/471 (Ref.)
1369/3100.0081.48 (1.11-1.98)216/790.1251.35 (0.92-1.97)216/790.0171.72 (1.10-2.69)
2133/1480.7821.05 (0.74-1.49)47/1060.6550.90 (0.56-1.44)86/420.3631.270.76-2.14)
Ptrend = 0.528Ptrend = 0.720Ptrend = 0.349
ERCC5 rs873601-GSTP1 rs1695on AG risk
0321/2791 (Ref.)138/2061 (Ref.)183/731 (Ref.)
1254/2860.0130.73 (0.57-0.94)99/2010.0610.73 (0.53-1.02)155/850.0900.72 (0.49-1.05)
259/550.6700.911 (0.60-1.40)20/450.1500.66 (0.37-1.16)39/100.2411.57 (0.74-3.31)
Ptrend = 0.156Ptrend = 0.043Ptrend = 0.907