APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans

doi:10.3748/wjg.v20.i26.8700

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Jul 14, 2014; 20(26): 8700-8708
Published online Jul 14, 2014. doi: 10.3748/wjg.v20.i26.8700

Table 1 Primer sequences

Target gene	Sequence of primers	Allele and PCR product size (bp)
OGG1	F1: 5’-CAGCCCAGACCCAGTGGACTC-3’	C allele (252 bp)
Ser326Cys	R1: 5’-TGGCTCCTGAGCATGGCGGG-3’	C allele (252 bp)
	F2: 5’-CAGTGCCGACCTGCGCCAATG-3’	G allele (194 bp)
	R2: 5’-GGTAGTCACAGGGAGGCCCC-3’	G allele (194 bp)
XRCC1	F1: 5’-TCCCTGCGCCGCTGCAGTTTCT-3’	G allele (447 bp)
Arg399Gln	R1: 5’-TGGCGTGTGAGGCCTTACCTCC-3’	G allele (447 bp)
	F2: 5’-TCGGCGGCTGCCCTCCCA-3’	A allele (222 bp)
	R2: 5’-AGCCCTCTGTGACCTCCCAGGC-3’	A allele (222 bp)
APE1	F1: 5’-CCTACGGCATAGGTGAGACC-3’	G allele (167 bp)
Asp148Glu	R1: 5’-TCCTGATCATGCTCCTCC-3’	G allele (167 bp)
	F2: 5’-TCTGTTTCATTTCTATAGGCGAT-3’	T allele (236 bp)
	R2: 5’-GTCAATTTCTTCATGTGCCA-3’	T allele (236 bp)
APE1 promoter	F1: 5’-CTAACTGCCAGGGACGCCGA-3’	T allele (136 bp)
-141T/G	R1: 5’-ACACTGACTTAAGATTCTAACTA-3’	T allele (136 bp)
	F2: 5’-ACTGTTTTTTTCCCTCTTGCACAG-3’	G allele (335 bp)
	R2: 5’-TGAGCAAAAGAGCAACCCCG-3’	G allele (335 bp)

PCR: Polymerase chain reaction; OGG1: 8-oxoguanine DNA-glycosylase 1; APE1: Apurinic endonuclease 1; XRCC1: X-ray repair cross-complementing protein 1.

Table 2 Demographic characteristics of colorectal cancer cases and control participants n (%)

Variables	Cases (n = 247)	Controls (n = 300)	P value
Age¹
Mean age ± SE	59.22 ± 14.54	56.96 ± 15.84	0.574
< 60 yr	120 (48.58)	153 (51.00)
≥ 60 yr	127 (51.42)	147 (49.00)
Gender			0.930
Male	145 (58.70)	175 (58.33)
Female	102 (41.30)	125 (41.67)
Family history of cancer			0.633
No	214 (86.64)	264 (88.00)
Yes	33 (13.36)	36 (12.00)
Smoking			0.801
Nonsmokers	159 (64.37)	190 (63.33)
Smokers	88 (35.63)	110 (36.67)
Alcohol consumption			0.749
Nondrinkers	176 (71.25)	210 (70.00)
Drinkers	71 (28.75)	90 (30.00)
Body mass index			0.968
< 18.5	9 (3.64)	12 (4.00)
18.5-24.9	37 (14.98)	46 (15.33)
≥ 25	201 (81.38)	242 (80.67)

¹Age is a continuous variable in the regression model analysis.

Table 3 Gene distributions n (%)

Genes			Cases (n = 247)	Controls (n = 300)	Crude OR (95%CI)¹	P value¹	Adjusted OR (95%CI)²	P value²
OGG1	Genotype	Ser/Ser	44 (17.81)	48 (16.00)	1.000		1.000
Ser326Cys		Ser/Cys	111 (44.94)	139 (46.33)	0.871 (0.540-1.407)	0.572	0.862 (0.532-1.395)	0.546
		Cys/Cys	92 (37.25)	113 (37.67)	0.888 (0.542-1.454)	0.637	0.914 (0.556-1.502)	0.723
	Allele	Ser	199 (40.28)	235 (39.17)	1.000
	Allele	Cys	295 (59.72)	365 (60.83)	0.954 (0.748-1.217)	0.707
XRCC1	Genotype	Arg/Arg	131 (53.04)	142 (47.33)	1.000		1.000
Gln399Arg		Arg/Gln	91 (36.84)	132 (44.00)	0.747 (0.523-1.068)	0.110	0.744 (0.519-1.066)	0.107
		Gln/Gln	25 (10.12)	26 (8.67)	1.042 (0.573-1.896)	0.892	1.055 (0.577-1.930)	0.862
	Allele	Arg	353 (71.46)	416 (69.33)	1.000
	Allele	Gln	141 (28.54)	184 (30.67)	0.903 (0.695-1.173)	0.444
APE1	Genotype	Asp/Asp	87 (35.22)	122 (40.66)	1.000		1.000
Asp148Glu		Asp/Glu	90 (36.44)	137 (45.67)	0.921 (0.628-1.351)	0.674	0.939 (0.639-1.379)	0.747
		Glu/Glu	70 (28.34)	41 (13.67)	2.394 (1.491-3.844)	< 0.001	2.411 (1.497-3.886)	< 0.001
	Allele	Asp	264 (53.44)	381 (63.50)	1.000
	Allele	Glu	230 (46.56)	219 (36.50)	1.516 (1.189-1.932)	0.001
APE1 promoter	Genotype	TT	93 (37.65)	93 (31.00)	1.000		1.000
-141T/G		TG	102 (41.30)	140 (46.67)	0.729 (0.496-1.070)	0.106	0.748 (0.508-1.104)	0.144
		GG	52 (21.05)	67 (22.33)	0.776 (0.489-1.232)	0.282	0.781 (0.490-1.247)	0.301
	Allele	T	288 (58.30)	326 (54.33)	1.000
	Allele	G	206 (41.70)	274 (45.67)	0.851 (0.669-1.082)	0.188

¹Obtained by χ² test, and the significance level was adjusted to 0.0125;

²Adjusted with age, gender, smoking status, alcohol consumption, body mass index, and family history of cancer. OGG1: 8-oxoguanine DNA-glycosylase 1; APE1: Apurinic endonuclease 1; XRCC1: X-ray repair cross-complementing protein 1.

Table 4 Distribution of genotypes and odds ratios for colorectal cancer stratified by smoking status

	Non-smokers			Smokers			P interaction
	Case/control	OR (95%CI)¹	P value	Case/control	OR (95%CI)¹	P value
OGG1 Ser326Cys							0.432
Ser/Ser	30/32	1.000		14/16	1.000
Ser/Cys	75/86	0.921 (0.505-1.679)	0.788	36/53	0.753 (0.315-1.798)	0.523
Cys/Cys	54/72	0.850 (0.454-1.593)	0.613	38/41	1.087 (0.452-2.612)	0.853
XRCC1 Arg399Gln							0.003
Arg/Arg + Gln/Gln	93/118	1.000		63/50	1.000
Arg/Gln	66/72	1.120 (0.720-1.743)	0.614	25/60	0.289 (0.152-0.548)	< 0.001
APE1 Asp148Glu							0.706
Asp/Asp	58/80	1.000		29/42	1.000
Asp/Glu	60/84	1.089 (0.669-1.772)	0.733	30/53	0.867 (0.433-1.735)	0.687
Glu/Glu	41/26	2.356 (1.273-4.360)	0.006	29/15	3.299 (1.428-7.623)	0.005
APE1 -141T/G							0.858
TT	59/55	1.000		34/38	1.000
TG	66/91	0.668 (0.404-1.107)	0.118	36/49	0.796 (0.406-1.562)	0.507
GG	34/44	0.659 (0.361-1.201)	0.173	18/23	0.794 (0.352-1.791)	0.794

¹Adjusted for age, gender, alcohol consumption, body mass index, and family history of cancer. OGG1: 8-oxoguanine DNA-glycosylase 1; APE1: Apurinic endonuclease 1; XRCC1: X-ray repair cross-complementing protein 1.

Table 5 Distribution of genotypes and odds ratios for colorectal cancer stratified by alcohol consumption

	Non-drinkers			Drinkers			P interaction
	Case/control	OR (95%CI)¹	P value	Case/control	OR (95%CI)¹	P value
OGG1 Ser326Cys							0.068
Ser/Ser	33/32	1.000		11/16	1.000
Ser/Cys	87/98	0.888 (0.500-1.576)	0.684	24/41	0.793 (0.296-2.119)	0.643
Cys/Cys	56/80	0.728 (0.397-1.332)	0.303	36/33	1.806 (0.685-4.760)	0.232
XRCC1 Arg399Gln							0.174
Arg/Arg + Gln/Gln	106/121	1.000		50/47	1.000
Arg/Gln	70/89	0.909 (0.600-1.376)	0.651	21/43	0.327 (0.158-0.673)	0.002
APE1 Asp148Glu							0.848
Asp/Asp	62/89	1.000		25/33	1.000
Asp/Glu	64/92	1.043 (0.656-1.660)	0.857	26/45	0.816 (0.379-1.756)	0.603
Glu/Glu	50/29	2.654 (1.489-4.730)	0.001	20/12	2.095 (0.819-5.360)	0.123
APE1 -141T/G							0.618
TT	68/63	1.000		25/30	1.000
TG	72/98	0.651 (0.405-1.045)	0.076	30/42	0.805 (0.374-1.734)	0.580
GG	36/49	0.612 (0.346-1.082)	0.091	16/18	0.912 (0.366-2.270)	0.842

¹Adjusted for age, gender, smoking status, body mass index, and family history of cancer. OGG1: 8-oxoguanine DNA-glycosylase 1; APE1: Apurinic endonuclease 1; XRCC1: X-ray repair cross-complementing protein 1.

Table 6 Distribution of genotypes and odds ratios for colorectal cancer stratified by body mass index

	< 25 kg/m²			≥25 kg/m²			P interaction
	Case/control	OR (95%CI)¹	P value	Case/control	OR (95%CI)¹	P value
OGG1 Ser326Cys							0.706
Ser/Ser	9/8	1.000		35/40	1.000
Ser/Cys	17/26	0.529 (0.149-1.880)	0.325	94/113	0.973 (0.567-1.668)	0.920
Cys/Cys	20/24	0.936 (0.269-3.258)	0.917	72/89	0.938 (0.536-1.643)	0.823
XRCC1 Arg399Gln							0.755
Arg/Arg + Gln/Gln	27/32	1.000		129/136	1.000
Arg/Gln	19/26	0.928 (0.396-2.175)	0.863	72/106	0.754 (0.510-1.114)	0.156
APE1 Asp148Glu							0.725
Asp/Asp	17/22	1.000		70/100	1.000
Asp/Glu	13/25	0.609 (0.222-1.674)	0.337	77/112	1.023 (0.666-1.571)	0.919
Glu/Glu	16/11	1.770 (0.594-5.274)	0.305	54/30	2.581 (1.489-4.474)	0.001
APE1 -141T/G							0.044
TT	17/9	1.000		76/84	1.000
TG	15/33	0.214 (0.069-0.660)	0.007	87/107	0.934 (0.608-1.434)	0.754
GG	14/16	0.406 (0.122-1.352)	0.142	38/51	0.860 (0.506-1.462)	0.577

Citation: Zhang SH, Wang LA, Li Z, Peng Y, Cun YP, Dai N, Cheng Y, Xiao H, Xiong YL, Wang D. APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans. World J Gastroenterol 2014; 20(26): 8700-8708
URL: https://www.wjgnet.com/1007-9327/full/v20/i26/8700.htm
DOI: https://dx.doi.org/10.3748/wjg.v20.i26.8700