Contribution of ZBTB20 Polymorphisms to Esophageal Cancer Risk Among the Chinese Han Population

Figures & data

Table 1 The Information of the Patients with Esophageal Cancer and Healthy Controls

Characteristics	Case	Control	p
Number	525	522
Age (mean ± SD, years)	63.92 ± 9.18	63.70 ± 7.07	0.657
> 65	236 (45.0%)	191 (36.6%)
≤ 65	289 (55.0%)	331 (63.4%)
Gender			0.956
Male	390 (74.3%)	387 (74.1%)
Female	135 (25.7%)	135 (25.9%)	<0.001
BMI (kg/m^2)
≤ 24	435 (82.9%)	162 (31.0%)
> 24	74 (14.1%)	193 (37.0%)
Missing	16 (3.0%)	167 (32.0%)
Smoking			0.040
Yes	245 (46.7%)	117 (22.4%)
No	274 (52.2%)	179 (34.3%)
Missing	6 (1.1%)	226 (43.3%)
Drinking			<0.001
Yes	125 (23.8%)	116 (22.2%)
No	354 (67.4%)	155 (29.7%)
Missing	46 (8.8%)	251 (48.1%)
Pathological type
Squamous cell carcinoma	387 (73.7%)
Other	138 (26.3%)
Lymph node metastasis
Yes	177 (33.7%)
No	162 (30.9%)
Missing	186 (35.4%)
Clinical stages
I+II	159 (30.3%)
III+IV	189 (36.0%)
Missing	177 (33.7%)

Note: p values were calculated by χ² test or the Student’s t-test.

Table 2 The Information of Four Polymorphisms on the ZBTB20 Gene

SNP ID	Chr: Position	Alleles (Ref/Alt)	MAF		Call rate	HWE			Frequency^a				HaploReg v4.1
			Cases	Controls		O(HET)	E(HET)	p	AFR	AMR	ASN	EUR
rs10934270	3:114384900	C/T	0.069	0.103	100.0%	0.176	0.186	0.239	0.05	0.39	0.11	0.43	DNAse, Motifs Changed, Selected eQTL hits
rs9288999	3:114429080	A/G	0.416	0.430	99.9%	0.488	0.490	0.929	0.67	0.41	0.43	0.24	Enhancer histone marks, Motifs changed
rs9841504	3:114643917	C/G	0.147	0.139	100.0%	0.251	0.239	0.359	0.34	0.17	0.16	0.08	Enhancer histone marks, Motifs changed
rs73230612	3:115131989	T/C	0.404	0.416	100.0%	0.475	0.486	0.652	0.81	0.83	0.40	0.89	Motifs changed
SNP ID	RegulomeDB		Pair of SNPs with r^2 ≥ 0.8^a
rs10934270	TF binding + any motif + DNase peak		rs6801183, rs9846724, rs62265723, rs13084997, rs1830095, rs1474426, rs1474425, rs2722004, rs7626635, rs10934269, rs2733405, rs12491672, rs2683792, rs2683791, rs2722007, rs2722006, rs2722005, rs6775754, rs9881173, rs9881461
rs9288999	Other		rs13090443, rs13091312, rs2722019, rs4580516, rs146634908, rs9840030, rs10934272, rs9882269, rs13067741, rs9816740, rs10470388, rs10470389, rs7630111
rs9841504	Motif hit		rs11294002, rs1290894, rs9820958, rs1274265, rs73857635, rs9878038, rs9841454, rs56298435, rs16823073, rs74848785, rs76819674, rs78502125, rs77352581, rs78889361, rs76373676, rs116319741, rs150495605
rs73230612	Other		rs77093417, rs10222496, rs16823443, rs7643617, rs6805723, rs1473580, rs9815319, rs9830947, rs2177039, rs16823508, rs12639377, rs13323268, rs12632241, rs73230612, rs66839906, rs199713828, rs9879646, rs114072304, rs7620646, rs73230620, rs141794376, rs56260350, rs9832181, rs980944, rs7653569, rs60015778, rs201752575, rs75352178, rs16823578, rs9822860, rs59774725, rs9790250, rs11712587, rs78572299, rs9867281, rs11718803, rs13318807, rs6768463, rs13326167, rs6806156, rs11706205, rs9811889

Notes: ^aData from Haploreg (https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php). RegulomeDB (https://regulome.stanford.edu/regulome-search/).

Abbreviations: SNP, Single nucleotide polymorphism; MAF, Minor allele frequency; HWE, Hardy-Weinberg equilibrium; O(HET), Observed heterozygosity frequency; E(HET), Expected heterozygosity frequency; AFR, African; AMR, American; ASN, Asian; EUR, European.

Table 3 Risk Analysis for ZBTB20 Polymorphisms and Esophageal Cancer in Different Genetic Models by Logistic Regression Analysis

SNP	Model	Genotype	Controls	Esophageal Cancer			Esophageal Squamous Cell Carcinoma
				Cases	OR (95% CI)	p-value	Cases	OR (95% CI)	p-value
rs10934270	Allele	C	936	978	1		719	1
		T	108	72	0.64 (0.47–0.87)	0.004*	55	0.66 (0.47–0.93)	0.017
	Genotype	CC	422	455	1		334	1
		CT	92	68	0.68 (0.49–0.96)	0.029	51	0.70 (0.48–1.02)	0.061
		TT	8	2	0.23 (0.05–1.10)	0.065	2	0.32 (0.07–1.50)	0.147
	Dominant	CC	422	455	1		334	1
		CT-TT	100	70	0.65 (0.46–0.91)	0.011*	53	0.67 (0.47–0.96)	0.031
	Recessive	CC-CT	514	523	1		385	1
		TT	8	2	0.25 (0.05–1.16)	0.077	2	0.33 (0.07–1.58)	0.167
	Log-additive				0.64 (0.47–0.88)	0.005*		0.67 (0.48–0.94)	0.020
rs9288999	Allele	A	594	613	1		462	1
		G	448	437	0.95 (0.79–1.12)	0.524	312	0.90 (0.74–1.08)	0.252
	Genotype	AA	170	180	1		137	1
		AG	254	253	0.94 (0.72–1.24)	0.665	188	0.92 (0.69–1.23)	0.572
		GG	97	92	0.90 (0.63–1.28)	0.551	62	0.79 (0.54–1.17)	0.249
	Dominant	AA	170	180	1		137	1
		AG-GG	351	345	0.93 (0.72–1.20)	0.578	250	0.88 (0.67–1.17)	0.387
	Recessive	AA-AG	424	433	1		325	1
		GG	97	92	0.93 (0.68–1.28)	0.654	62	0.84 (0.59–1.19)	0.314
	Log-additive				0.95 (0.80–1.13)	0.535		0.90 (0.74–1.08)	0.256
rs9841504	Allele	C	899	896	1		649	1
		G	145	154	1.07 (0.83–1.36)	0.611	125	1.19 (0.92–1.55)	0.180
	Genotype	CC	384	386	1		275	1
		CG	131	124	0.94 (0.71–1.25)	0.664	99	1.06 (0.78–1.43)	0.731
		GG	7	15	2.12 (0.85–5.26)	0.106	13	2.59 (1.02–6.59)	0.045
	Dominant	CC	384	386	1		275	1
		CG-GG	138	139	1.00 (0.76–1.32)	0.992	112	1.13 (0.84–1.52)	0.408
	Recessive	CC-CG	515	510	1		374	1
		GG	7	15	2.15 (0.87–5.33)	0.098	13	2.56 (1.01–6.47)	0.047
	Log-additive				1.06 (0.83–1.36)	0.630		1.19 (0.92–1.55)	0.183
rs73230612	Allele	T	610	626	1		450	1
		C	434	424	0.95 (0.80–1.13)	0.580	324	1.01 (0.84–1.22)	0.902
	Genotype	TT	181	184	1		127	1
		TC	248	258	1.03 (0.78–1.34)	0.853	196	1.13 (0.84–1.52)	0.416
		CC	93	83	0.88 (0.61–1.26)	0.475	64	0.98 (0.66–1.45)	0.920
	Dominant	TT	181	184	1		127	1
		TC-CC	341	341	0.99 (0.76–1.27)	0.907	260	1.09 (0.82–1.44)	0.549
	Recessive	TT-TC	429	422	1		323	1
		CC	93	83	0.86 (0.62–1.20)	0.378	64	0.91 (0.64–1.29)	0.606
	Log-additive				0.95 (0.80–1.13)	0.580		1.01 (0.84–1.22)	0.899

Notes: p values were calculated by logistic regression analysis with adjustments for age and gender. Bold p < 0.05 respects the data is statistically significant. *p indicate that after Bonferroni correction (p < 0.05/4) means the data is statistically significant.

Abbreviations: SNP, single nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval.

Table 4 Stratified Analysis by Gender and Age for the Associations Between ZBTB20 Polymorphisms and the Risk of Esophageal Cancer

SNP ID	Model	Genotype	Control	Case	OR (95% CI)	p–value	Control	Case	OR (95% CI)	p–value
Gender			Males				Females
rs10934270	Allele	C	699	730	1		237	248	1
		T	75	50	0.64 (0.44–0.93)	0.017	33	22	0.64 (0.36–1.12)	0.118
	Genotype	CC	317	342	1		105	113	1
		CT	65	46	0.66 (0.44–0.99)	0.042	27	22	0.76 (0.41–1.41)	0.381
		TT	5	2	0.37 (0.07–1.92)	0.237	3	0	/	/
	Dominant	CC/ CT-TT	317/70	342/48	0.64 (0.43–0.95)	0.025	105/30	113/22	0.68 (0.37–1.26)	0.219
	Recessive	CC-CT/ TT	382/5	388/2	0.39 (0.08–2.04)	0.267	132/3	135/0	/	/
	Log-additive				0.65 (0.45–0.93)	0.020			0.64 (0.36–1.13)	0.122
rs73230612	Allele	T	459	452	1		151	174	1
		C	315	328	1.06 (0.86–1.29)	0.588	119	96	0.70 (0.50–0.99)	0.043
	Genotype	TT	142	132	1		39	52	1
		TC	175	188	1.16 (0.84–1.58)	0.364	73	70	0.72 (0.42–1.22)	0.220
		CC	70	70	1.07 (0.71–1.61)	0.739	23	13	0.42 (0.19–0.94)	0.035
	Dominant	TT/ TC-CC	142/245	132/258	1.13 (0.84–1.52)	0.409	39/96	52/83	0.65 (0.39–1.08)	0.097
	Recessive	TT-TC/ CC	317/70	320/70	0.99 (0.68–1.42)	0.943	112/23	122/13	0.52 (0.25–1.08)	0.078
	Log-additive				1.05 (0.86–1.29)	0.605			0.67 (0.46–0.97)	0.034
rs9288999	Allele	A	437	467	1		157	146	1
		G	337	313	0.87 (0.71–1.06)	0.173	111	124	1.20 (0.85–1.69)	0.292
	Genotype	AA	124	143	1		46	37	1
		AG	189	181	0.83 (0.61–1.14)	0.251	65	72	1.38 (0.80–2.38)	0.251
		GG	74	66	0.78 (0.51–1.17)	0.225	23	26	1.41 (0.69–2.86)	0.347
	Dominant	AA/ AG-GG	124/263	143/247	0.82 (0.61–1.10)	0.179	46/88	37/98	1.39 (0.82–2.33)	0.219
	Recessive	AA-AG/ GG	313/74	324/66	0.86 (0.60–1.25)	0.434	111/23	109/26	1.15 (0.62–2.14)	0.657
	Log-additive				0.87 (0.71–1.07)	0.183			1.21 (0.85–1.71)	0.284
rs9841504	Allele	C	667	672	1		232	224	1
		G	107	108	1.00 (0.75–1.34)	0.990	38	46	1.25 (0.79–2.00)	0.342
	Genotype	CC	286	291	1		98	95	1
		CG	95	90	0.93 (0.67–1.29)	0.660	36	34	0.97 (0.56–1.68)	0.916
		GG	6	9	1.46 (0.51–4.15)	0.483	1	6	6.20 (0.73–52.44)	0.094
	Dominant	CC/ CG-GG	286/101	291/99	0.96 (0.70–1.32)	0.801	98/37	95/40	1.11 (0.66–1.89)	0.693
	Recessive	CC-CG/ GG	381/6	381/9	1.48 (0.52–4.21)	0.460	134/1	129/6	6.24 (0.74–52.59)	0.092
	Log-additive				1.00 (0.75–1.33)	0.987			1.25 (0.78–1.99)	0.350
Age, years			> 65				≤ 65
rs10934270	Allele	C	351	429	1		585	549	1
		T	31	43	1.14 (0.70–1.84)	0.607	77	29	0.40 (0.26–0.62)	3.25×10^−5*
	Genotype	CC	161	194	1		261	261	1
		CT	29	41	1.19 (0.70–2.01)	0.519	63	27	0.40 (0.25–0.66)	3.29×10^−4*
		TT	1	1	0.85 (0.05–13.81)	0.909	7	1	0.19 (0.02–1.54)	0.119
	Dominant	CC/ CT-TT	161/30	194/42	1.18 (0.70–1.98)	0.538	261/70	261/28	0.38 (0.24–0.62)	1.07×10^−4*
	Recessive	CC-CT/ TT	190/1	235/1	0.83 (0.05–13.40)	0.893	324/7	288/1	0.21 (0.03–1.73)	0.147
	Log-additive				1.15 (0.70–1.90)	0.571			0.41 (0.26–0.64)	1.15×10^−4*
rs9288999	Allele	A	225	266	1		369	347	1
		G	157	206	1.11 (0.84–1.46)	0.455	291	231	0.84 (0.67–1.06)	0.143
	Genotype	AA	65	78	1		105	102	1
		AG	95	110	0.93 (0.60–1.44)	0.751	159	143	0.87 (0.60–1.25)	0.440
		GG	31	48	1.21 (0.69–2.14)	0.505	66	44	0.56 (0.34–0.91)	0.019
	Dominant	AA/ AG-GG	65/126	78/158	1.00 (0.66–1.51)	0.995	105/225	102/187	0.77 (0.55–1.09)	0.146
	Recessive	AA-AG/ GG	160/31	188/48	1.26 (0.76–2.09)	0.363	264/66	245/44	0.61 (0.39–0.94)	0.025
	Log-additive				1.07 (0.82–1.41)	0.613			0.77 (0.60–0.97)	0.027
rs9841504	Allele	C	329	393	1		570	503	1
		G	53	79	1.25 (0.86–1.82)	0.250	92	75	0.92 (0.67–1.28)	0.635
	Genotype	CC	141	166	1		243	220	1
		CG	47	61	1.09 (0.7–1.71)	0.697	84	63	0.89 (0.61–1.30)	0.546
		GG	3	9	2.56 (0.67–9.76)	0.168	4	6	1.85 (0.50–6.81)	0.358
	Dominant	CC/ CG-GG	141/50	166/70	1.18 (0.77–1.82)	0.451	243/88	220/69	0.93 (0.64–1.35)	0.707
	Recessive	CC-CG/ GG	188/3	227/9	2.5 (0.66–9.49)	0.177	327/4	283/6	1.90 (0.52–6.99)	0.335
	Log-additive				1.23 (0.85–1.8)	0.275			0.99 (0.70–1.38)	0.933
rs73230612	Allele	T	223	283	1		387	343	1
		C	159	189	0.94 (0.71–1.23)	0.640	275	235	0.96 (0.77–1.21)	0.753
	Genotype	TT	62	87	1		119	97	1
		TC	99	109	0.80 (0.52–1.23)	0.309	149	149	1.19 (0.83–1.70)	0.353
		CC	30	40	0.92 (0.51–1.65)	0.781	63	43	0.83 (0.51–1.35)	0.459
	Dominant	TT/ TC-CC	62/129	87/149	0.83 (0.55–1.24)	0.365	119/212	97/192	1.08 (0.77–1.52)	0.650
	Recessive	TT-TC/ CC	161/30	196/40	1.05 (0.62–1.77)	0.862	268/63	246/43	0.75 (0.49–1.17)	0.204
	Log-additive				0.93 (0.70–1.23)	0.593			0.96 (0.76–1.21)	0.706

Notes: p values were calculated by logistic regression analysis with adjustments for age and gender. Bold p < 0.05 respects the data is statistically significant. *p indicate that after Bonferroni correction (p < 0.05/4) means the data is statistically significant.

Abbreviations: SNP, single nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval.

Table 5 Stratified Analysis by BMI and Smoking for the Associations Between ZBTB20 Polymorphisms and the Risk of Esophageal Cancer

SNP ID	Model	Genotype	Control	Case	OR (95% CI)	p–value	Control	Case	OR (95% CI)	p–value
BMI, kg/m^2			> 24				≤ 24
rs10934270	Allele	C	356	135	1		277	812	1
		T	30	13	1.14 (0.58–2.26)	0.701	47	58	0.42 (0.28–0.63)	2.11×10^−5*
	Genotype	CC	164	61	1		120	379	1
		CT	28	13	1.30 (0.62–2.73)	0.484	37	54	0.48 (0.30–0.77)	0.002*
		TT	1	0	/	/	5	2	0.13 (0.03–0.71)	0.018
	Dominant	CC/ CT-TT	164/29	61/13	1.26 (0.6–2.64)	0.534	120/42	379/56	0.44 (0.28–0.69)	3.64×10^−4*
	Recessive	CC-CT/ TT	192/1	74/0	/	/	157/5	433/2	0.15 (0.03–0.81)	0.027
	Log-additive				1.21 (0.59–2.47)	0.605			0.45 (0.30–0.68)	1.35×10^−4*
rs9288999	Allele	A	212	83	1		186	507	1
		G	174	65	0.95 (0.65–1.40)	0.810	136	363	0.98 (0.76–1.27)	0.874
	Genotype	AA	58	24	1		55	148	1
		AG	96	35	0.89 (0.47–1.67)	0.707	76	211	1.07 (0.71–1.61)	0.754
		GG	39	15	0.86 (0.39–1.90)	0.717	30	76	0.95 (0.56–1.61)	0.858
	Dominant	AA/ AG-GG	58/135	24/50	0.88 (0.49–1.59)	0.671	55/106	148/287	1.04 (0.70–1.52)	0.862
	Recessive	AA-AG/ GG	154/39	59/15	0.93 (0.47–1.85)	0.838	131/30	359/76	0.92 (0.57–1.47)	0.719
	Log-additive				0.92 (0.63–1.37)	0.695			0.99 (0.76–1.28)	0.937
rs9841504	Allele	C	334	125	1		281	741	1
		G	52	33	1.18 (0.69–2.01)	0.538	43	129	1.14 (0.78–1.65)	0.496
	Genotype	CC	141	54	1		120	318	1
		CG	52	17	0.81 (0.42–1.56)	0.529	41	105	0.99 (0.65–1.51)	0.963
		GG	0	3	/	/	1	12	4.96 (0.63–38.90)	0.127
	Dominant	CC/ CG-GG	141/52	54/20	0.96 (0.52–1.80)	0.907	120/42	318/117	1.08 (0.71–1.64)	0.713
	Recessive	CC-CG/ GG	193/0	71/3	/	/	161/1	426/12	4.98 (0.64–38.88)	0.126
	Log-additive				1.16 (0.66–2.05)	0.613			1.17 (0.81–1.70)	0.408
rs73230612	Allele	T	214	93	1		190	517	1
		C	172	55	0.74 (0.50–1.09)	0.122	134	353	0.97 (0.75–1.26)	0.807
	Genotype	TT	59	31	1		54	149	1
		TC	96	31	0.59 (0.32–1.09)	0.092	82	219	1.00 (0.67–1.50)	0.993
		CC	38	12	0.63 (0.28–1.41)	0.261	26	67	0.92 (0.53–1.61)	0.782
	Dominant	TT/ TC-CC	59/134	31/43	0.60 (0.34–1.07)	0.082	54/108	149/286	0.98 (0.67–1.44)	0.918
	Recessive	TT-TC/ CC	155/38	62/12	0.85 (0.41–1.77)	0.667	136/26	368/67	0.93 (0.56–1.52)	0.761
	Log-additive				0.75 (0.50–1.12)	0.159			0.97 (0.74–1.27)	0.816
Smoking			Yes				No
rs10934270	Allele	C	206	459	1		319	507	1
		T	28	31	0.50 (0.29–0.85)	0.009*	39	41	0.66 (0.42–1.05)	0.077
	Genotype	CC	91	216	1		144	233	1
		CT	24	27	0.43 (0.24–0.79)	0.006*	31	41	0.81 (0.49–1.36)	0.431
		TT	2	2	0.38 (0.05–2.72)	0.334	4	0	/	/
	Dominant	CC/ CT-TT	91/26	216/29	0.43 (0.24–0.77)	0.004*	144/35	233/41	0.72 (0.43–1.18)	0.188
	Recessive	CC-CT/ TT	115/2	243/2	0.43 (0.06–3.12)	0.406	175/4	274/0	/	/
	Log-additive				0.47 (0.28–0.81)	0.006*			0.65 (0.41–1.03)	0.069
rs9841504	Allele	C	214	420	1		301	464	1
		G	20	70	1.78 (1.06–3.01)	0.029	57	84	0.96 (0.66–1.38)	0.810
	Genotype	CC	97	181	1		124	199	1
		CG	20	58	1.51 (0.84–2.69)	0.166	53	66	0.77 (0.5–1.18)	0.229
		GG	0	6	/	/	2	9	2.69 (0.57–12.74)	0.211
	Dominant	CC/ CG-GG	97/20	181/64	1.65 (0.93–2.94)	0.086	124/55	199/75	0.84 (0.55–1.28)	0.413
	Recessive	CC-CG/ GG	117/0	239/6	/	/	177/2	265/9	2.89 (0.61–13.61)	0.179
	Log-additive				1.72 (1.01–2.95)	0.047			0.94 (0.65–1.37)	0.762
rs9288999	Allele	A	137	289	1		204	314	1
		G	97	201	0.98 (0.72–1.35)	0.912	154	234	0.99 (0.75–1.29)	0.925
	Genotype	AA	44	86	1		62	90	1
		AG	49	117	1.10 (0.66–1.83)	0.711	80	134	1.10 (0.72–1.70)	0.653
		GG	24	42	0.85 (0.45–1.62)	0.630	37	50	0.89 (0.52–1.54)	0.688
	Dominant	AA/ AG-GG	44/73	86/159	1.02 (0.64–1.64)	0.924	62/117	90/184	1.04 (0.69–1.55)	0.854
	Recessive	AA-AG/ GG	93/24	203/42	0.81 (0.46–1.44)	0.470	142/37	224/50	0.84 (0.52–1.36)	0.489
	Log-additive								0.97 (0.74–1.26)	0.794
rs73230612	Allele	T	130	275	1		215	345	1
		C	104	215	0.98 (0.71–1.34)	0.886	143	203	0.88 (0.67–1.16)	0.380
	Genotype	TT	38	79	1		63	104	1
		TC	54	117	1.02 (0.61–1.71)	0.949	89	137	0.91 (0.60–1.38)	0.658
		CC	25	49	0.93 (0.49–1.76)	0.831	27	33	0.73 (0.40–1.33)	0.302
	Dominant	TT/ TC-CC	38/79	79/166	0.99 (0.61–1.61)	0.971	63/116	104/170	0.87 (0.58–1.29)	0.484
	Recessive	TT-TC/ CC	92/25	196/49	0.92 (0.53–1.61)	0.781	152/27	241/33	0.77 (0.44–1.33)	0.350
	Log-additive								0.87 (0.65–1.15)	0.326

Notes: p values were calculated by logistic regression analysis with adjustments for age and gender. Bold p < 0.05 respects the data is statistically significant. *p indicate that after Bonferroni correction (p < 0.05/4) means the data is statistically significant.

Abbreviations: SNP, single nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval.

Table 6 False-Positive Report Probability Values for the Associations Between ZBTB20 Polymorphisms and Esophageal Cancer Susceptibility

Group/SNPs ID	Model	OR (95% CI)	p	Statistical Power	Prior Probability
					0.25	0.1	0.01	0.001	0.0001
Overall
rs10934270	Allele	0.64 (0.47–0.87)	0.004	0.942	0.014	0.040	0.315	0.823	0.979
	Genotype	0.68 (0.49–0.96)	0.029	0.960	0.081	0.210	0.745	0.967	0.997
	Dominant	0.65 (0.46–0.91)	0.011	0.906	0.091	0.232	0.768	0.971	0.997
	Log-additive	0.64 (0.47–0.88)	0.005	0.936	0.019	0.055	0.389	0.865	0.985
Esophageal squamous cell carcinoma
rs10934270	Allele	0.66 (0.47–0.93)	0.017	0.944	0.053	0.143	0.648	0.949	0.995
	Dominant	0.67 (0.47–0.96)	0.031	0.945	0.085	0.217	0.753	0.969	0.997
	Log-additive	0.67 (0.48–0.94)	0.020	0.955	0.060	0.162	0.679	0.955	0.995
rs9841504	Genotype	2.59 (1.02–6.59)	0.045	0.294	0.319	0.584	0.939	0.994	0.999
	Recessive	2.56 (1.01–6.47)	0.047	0.301	0.319	0.584	0.939	0.994	0.999
Males
rs10934270	Allele	0.64 (0.44–0.93)	0.017	0.902	0.060	0.161	0.679	0.955	0.995
	Genotype	0.66 (0.44–0.99)	0.042	0.910	0.128	0.306	0.829	0.980	0.998
	Dominant	0.64 (0.43–0.95)	0.025	0.890	0.083	0.213	0.749	0.968	0.997
	Log-additive	0.65 (0.45–0.93)	0.020	0.924	0.056	0.152	0.664	0.952	0.995
Females
rs73230612	Allele	0.70 (0.50–0.99)	0.043	0.971	0.119	0.288	0.817	0.978	0.998
	Genotype	0.42 (0.19–0.94)	0.035	0.336	0.237	0.483	0.911	0.990	0.999
	Log-additive	0.67 (0.46–0.97)	0.034	0.939	0.098	0.245	0.781	0.973	0.997
Age ≤ 65 years
rs10934270	Allele	0.40 (0.26–0.62)	3.25×10^−5	0.159	0.001	0.002	0.025	0.207	0.724
	Genotype	0.40 (0.25–0.66)	3.29×10^−4	0.191	0.005	0.016	0.148	0.637	0.946
	Dominant	0.38 (0.24–0.62)	1.07×10^−4	0.136	0.002	0.007	0.072	0.440	0.887
	Log-additive	0.41 (0.26–0.64)	1.15×10^−4	0.191	0.001	0.004	0.043	0.312	0.820
rs9288999	Genotype	0.56 (0.34–0.91)	0.019	0.676	0.079	0.204	0.738	0.966	0.996
	Recessive	0.61 (0.39–0.94)	0.025	0.816	0.084	0.216	0.752	0.968	0.997
	Log-additive	0.77 (0.60–0.97)	0.027	0.889	0.074	0.193	0.724	0.964	0.996
BMI ≤ 24 kg/m^2
rs10934270	Allele	0.42 (0.28–0.63)	2.11×10^−5	0.200	<0.001	0.001	0.013	0.121	0.579
	Genotype	0.48 (0.30–0.77)	0.002	0.433	0.016	0.046	0.348	0.844	0.982
		0.13 (0.03–0.71)	0.018	0.060	0.481	0.735	0.968	0.997	1.000
	Dominant	0.44 (0.28–0.69)	3.64×10^−4	0.289	0.004	0.011	0.107	0.546	0.923
	Recessive	0.15 (0.03–0.81)	0.027	0.081	0.505	0.753	0.971	0.997	1.000
	Log-additive	0.45 (0.30–0.68)	1.35×10^−4	0.308	0.001	0.004	0.046	0.327	0.829
Smokers
rs10934270	Allele	0.50 (0.29–0.85)	0.009	0.500	0.059	0.158	0.674	0.954	0.995
	Genotype	0.43 (0.24–0.79)	0.006	0.313	0.059	0.158	0.674	0.954	0.995
	Dominant	0.43 (0.24–0.77)	0.004	0.306	0.042	0.117	0.594	0.937	0.993
	Log-additive	0.47 (0.28–0.81)	0.006	0.412	0.046	0.125	0.612	0.941	0.994
rs9841504	Allele	1.78 (1.06–3.01)	0.029	0.668	0.124	0.298	0.823	0.979	0.998
	Log-additive	1.72 (1.01–2.95)	0.047	0.708	0.171	0.383	0.872	0.986	0.999

Notes: p values were calculated by logistic regression analysis with adjustments for age. Statistical power was calculated using the number of observations in the subgroup and the OR and p values in this table Bold prior probability < 0.2 (false-positive report probability threshold) respects the data is statistically significant.

Abbreviations: SNP, single nucleotide polymorphism; OR, odds ratio; 95% CI, 95% confidence interval.

Table 7 SNP–SNP Interaction Models of Candidate SNPs Analyzed by the MDR Method

Model	Training Bal. Acc.	Testing Bal. Acc.	CVC	p
rs10934270	0.5287	0.5297	10/10	0.0119
rs9288999, rs73230612	0.5412	0.4933	4/10	0.0187
rs10934270, rs9288999, rs73230612	0.5629	0.5211	9/10	<0.0001
rs10934270, rs9288999, rs9841504, rs73230612	0.5810	0.5086	10/10	<0.0001

Notes: p values were calculated using χ² tests. Bold indicate that p < 0.05 indicates statistical significance.

Abbreviations: MDR, multifactor dimensionality reduction; Bal. Acc., balanced accuracy; CVC, cross–validation consistency; OR, odds ratio; CI, confidence interval.

Figure 1 The dendrogram (A) and fruchterman Rheingold (B) of ZBTB20 SNP-SNP interaction for EC risk. (A) Short connections among nodes represent stronger interactions. (B) Positive percent entropy indicates synergistic interaction.