miRNA-146a rs2910164 C>G polymorphism increased the risk of esophagogastric junction adenocarcinoma: a case–control study involving 2,740 participants

Figures & data

Table 1 Distribution of selected demographic variables and risk factors in esophagogastric junction adenocarcinoma cases and controls

Variable	Overall cases (n=1,063)		Overall controls (n=1,677)		P-valuea
	n	%	n	%
Age, mean	64.19		63.91		0.451
(±SD)	(±8.63)		(±10.22)
Age (years)
<64	494	46.47	825	49.19	0.165
≥64	569	53.53	852	50.81
Sex
Male	759	71.40	1194	71.20	0.909
Female	304	28.60	483	28.80
Smoking status
Never	773	72.72	1323	78.89	<0.001
Ever	290	27.28	354	21.11
Alcohol use
Never	908	85.42	1507	89.86	<0.001
Ever	155	14.58	170	10.14
Lymph node status
Positive	625	58.80
Negative	438	41.20
Tumor–node–metastasis stage
I+II	305	28.69
III+IV	758	71.31

Notes:

a Two-sided chi-square and Student’s t-test. Bold values are statistically significant (P<0.05).

Table 2 Primary information for hsa-mir-146a rs2910164 C>G polymorphism

Genotyped polymorphism	hsa-mir-146a rs2910164 C>G
Chr	5
Position_37	160485411
Region	nc transcript variant
MAF for Chinese in database	0.43
MAF in our controls (n=1,677)	0.38
P-value for HWE test in our controls	0.919
% Genotyping value	99.09

Abbreviations: Chr, chromosome; HWE, Hardy–Weinberg equilibrium; MAF, minor allele frequency; nc, noncoding.

Table 3 The frequencies of miRNA-146a rs2910164 C>G polymorphisms in EGJA patients and controls

Genotype	Overall EGJA cases (n=1,063)		Overall controls (n=1,677)
	n	%	n	%
CC	327	31.41	644	38.47
CG	543	52.16	787	47.07
GG	171	16.43	243	14.52
CG+GG	714	68.59	1,030	61.53
CC+CG	870	83.57	1,431	85.48
GG	171	16.43	243	14.52
G allele	885	42.51	1,273	38.02

Abbreviation: EGJA, esophagogastric junction adenocarcinoma.

Table 4 miRNA-146a rs2910164 C>G polymorphism with esophagogastric junction adenocarcinoma

Genotype	Crude OR (95% CI)	P-value	Adjusted ORa (95% CI)	P-value
Additive model	1.28 (1.08–1.52)	0.005	1.27 (1.07–1.51)	0.006
Homozygote model	1.31 (1.03–1.65)	0.027	1.31 (1.03–1.65)	0.027
Dominant model	1.37 (1.16–1.61)	<0.001	1.36 (1.15–1.60)	<0.001
Recessive model	1.16 (0.94–1.43)	0.178	1.16 (0.94–1.44)	0.166

Notes:

a Adjusted for age, sex, smoking status, and alcohol use in a logistic regression model. Bold values are statistically significant (P<0.05).

Abbreviation: OR, odds ratio.

Table 5 Stratified analyses between miRNA-146a rs2910164 C>G polymorphism and EGJA risk by sex, age, smoking status, and alcohol consumption

Variable	miRNA-146a rs2910164 C>G (case/control)a			Adjusted ORb (95% CI); P-value
	CC	CG	GG	CC	CG	GG	CG/GG	GG vs (CG/CC)
Sex
Male	235/458	396/566	115/167	1.00	1.30 (1.06–1.59); P: 0.012	1.29 (0.97–1.71); P: 0.082	1.36 (1.12–1.65); P: 0.002	1.13 (0.87–1.46); P: 0.363
Female	92/186	147/221	56/76	1.00	1.23 (0.89–1.69); P: 0.215	1.35 (0.88–2.06); P: 0.171	1.39 (1.02–1.89); P: 0.040	1.25 (0.85–1.83); P: 0.263
Age
<64	153/335	256/374	73/114	1.00	1.39 (1.09–1.79); P: 0.009	1.32 (0.93–1.88); P: 0.121	1.48 (1.16–1.88); P: 0.001	1.12 (0.81–1.55); P: 0.481
≥64	174/309	287/413	98/129	1.00	1.18 (0.93–1.49); P: 0.176	1.28 (0.93–1.76); P: 0.136	1.27 (1.01–1.59); P: 0.042	1.18 (0.89–1.58); P: 0.250
Smoking status
Never	228/506	398/614	128/201	1.00	1.33 (1.09–1.63); P: 0.004	1.30 (0.99–1.70); P: 0.058	1.43 (1.18–1.73); P<0.001	1.13 (0.89–1.44); P: 0.325
Ever	99/138	145/173	43/42	1.00	1.09 (0.77–1.53); P: 0.638	1.37 (0.83–2.27); P: 0.221	1.16 (0.83–1.62); P: 0.376	1.32 (0.83–2.10); P: 0.247
Alcohol consumption
Never	282/585	461/697	144/223	1.00	1.28 (1.06–1.53); P: 0.009	1.24 (0.96–1.59); P: 0.097	1.36 (1.14–1.62); P<0.001	1.11 (0.88–1.39); P: 0.392
Ever	45/59	82/90	27/20	1.00	1.11 (0.67–1.85); P: 0.680	1.72 (0.84–3.54); P: 0.142	1.22 (0.75–1.99); P: 0.425	1.61 (0.84–3.08); P: 0.151

Notes:

a For miRNA-146a rs2910164 C>G, the genotyping was successful in 1,063 (97.93%) EGJA cases and 1,677 (99.82%) controls;

b Adjusted for multiple comparisons (age, sex, smoking status, and alcohol consumption [besides stratified factors accordingly]) in a logistic regression model. Bold values are statistically significant (P<0.05).

Abbreviations: EGJA, esophagogastric junction adenocarcinoma; OR, odds ratio.

Table 6 Logistic regression analyses of association between miRNA-146a rs2910164 C>G polymorphism and lymph node status in EGJA patients

Genotype	Positive (n=625)		Negative (n=438)		Crude OR (95% CI)	P-value	Adjusted ORa (95% CI)	P-value
	n	%	n	%
miRNA-146a rs2910164 C>G
CC	185	30.18	142	33.18	1.00		1.00
CG	327	53.34	216	50.47	1.17 (0.89–1.53)	0.264	1.16 (0.88–1.52)	0.299
GG	101	16.48	70	16.36	1.11 (0.77–1.61)	0.571	1.10 (0.76–1.60)	0.613
CG+GG	428	69.82	286	66.82	1.15 (0.88–1.50)	0.305	1.14 (0.87–1.48)	0.352
CC+CG	512	83.52	358	83.64	1.00		1.00
GG	101	16.48	70	16.36	1.01 (0.72–1.41)	0.959	1.01 (0.72–1.41)	0.975
G allele	529	43.15	356	41.59

Notes:

a Adjusted for age, sex, alcohol use, and smoking status.

Abbreviations: EGJA, esophagogastric junction adenocarcinoma; OR, odds ratio.