Association of TP73-AS1 gene polymorphisms with the risk and survival of gastric cancer in a Chinese Han Population

Figures & data

Table 1. Demographic information.

Characteristics	Cases (n = 1000)	Controls (n = 1000)	p
Age (years, mean ± SD)	62.3 ± 10.2	61.3 ± 13.7	.222
Sex
Male	679	645
Female	321	355	.108
Hypertension
No	657	624
Yes	343	376	.124
Diabetes
No	884	858
Yes	116	142	.083
Smoking status
No	718	807
Yes	282	193	<.001
Drinking status
No	789	864
Yes	211	136	<.001
Residence
Urban	399	498
Rural	601	502	<.001
Family History
No	944	988
Yes	56	12	<.001
Tumor differentiation
Well + moderate	559
Poor	441
Depth of tumor infiltration
T1	223
T2	134
T3	428
T4	215
Lymph node metastasis
Negative	367
Positive	633
Localization
Cardia	469
Noncardia	531

SD: standard deviation.

The significant results are in bold.

Table 2. Association between TP73-AS1 gene polymorphisms and risk of gastric cancer (rs1181865, rs3737589).

Genotype	Cases n	Controls n	Crude OR (95% CI)	p	Adjusted OR (95% CI)^a	p
overall	1000	1000
rs1181865
Additive model			1.19 (1.04–1.35)	.009	1.18 (1.04–1.35)	.013
Co-dominant model
AA	243	284	1		1
AG	523	522	1.17 (0.95–1.44)	.140	1.18 (0.95–1.46)	.133
GG	234	194	1.41 (1.09–1.82)	.009	1.38 (1.06–1.80)	.016
Dominant model
AA	243	284	1		1
AG + GG	757	716	1.24 (1.01–1.51)	.038	1.24 (1.01–1.52)	.043
Recessive model
AA + AG	766	806	1
GG	234	194	1.27 (1.02–1.57)	.029	1.25 (1.00–1.56)	.046
Allele
A	1009	1090	1
G	991	910	1.18 (1.04–1.33)	.010
HWE		0.097
rs3737589
Additive model			1.24 (1.07–1.44)	.004	1.26 (1.08–1.46)	.003
Co-dominant model
AA	507	570	1		1
AG	429	381	1.27 (1.06–1.52)	.011	1.25 (1.03–1.50)	.021
GG	64	49	1.47 (0.99–2.17)	.054	1.64 (1.10–2.45)	.016
Dominant model
AA	507	570	1		1
AG + GG	493	430	1.29 (1.08–1.54)	.005	1.29 (1.08–1.54)	.006
Recessive model
AA + AG	936	951	1
GG	64	49	1.32 (0.91–1.95)	.147	1.48 (1.00–2.18)	.051
Allele
A	1443	1521	1
G	557	479	1.23 (1.06–1.41)	.005
HWE		0.130

OR: odds ratio; CI: confidence interval; HWE: Hardy-Weinberg expectations.

^a Adjusted for age, sex, smoking status, drinking status, residence, hypertension, diabetes, and family history of GC in the logistic regression model.

The significant results are in bold.

Table 3a. Stratified analyses for TP73-AS1 genotypes in cases and controls (rs1181865).

Variable	n AG + GG /n AA for rs1181865		Logistic regression for rs1181865
	Cases	Controls	Adjusted OR (95% CI)^a	p
Age (y)
≥60	473/148	425/158	1.21 (0.93–1.59)	.157
＜60	284/95	291/126	1.30 (0.94–1.79)	.109
Sex
Females	247/74	255/100	1.30 (0.91–1.86)	.147
Males	510/169	461/184	1.20 (0.94–1.54)	.152
Smoking Status
Yes	217/65	141/52	1.28 (0.82–1.99)	.278
No	540/178	575/232	1.22 (0.97–1.54)	.089
Drinking Status
Yes	150/61	99/37	0.89 (0.54–1.46)	.642
No	607/182	617/247	1.32 (1.05–1.65)	.016
Residence
Rural	455/146	358/144	1.25 (0.95–1.64)	.116
Urban	302/97	358/140	1.23 (0.90–1.67)	.194
FH
Yes	41/15	10/2	0.62 (0.11–3.45)	.586
No	716/228	706/282	1.25 (1.02–1.54)	.033

OR: odds ratio; CI: confidence interval; FH: family history of GC.

^a Adjusted for age, sex, smoking status, drinking status, residence, hypertension, diabetes, and FH of GC (excluding the stratified factor in each stratum) in logistic regression model.

The significant results are in bold.

Table 3b. Stratified analyses for TP73-AS1 genotypes in cases and controls (rs3737589).

Variable	n AG + GG /n AA for rs3737589		Logistic regression for rs3737589
	Cases	Controls	Adjusted OR (95% CI)^a	p
Age (y)
≥60	323/298	261/322	1.37 (1.08–1.72)	.009
＜60	170/209	169/248	1.21 (0.91–1.62)	.189
Sex
Females	168/153	142/213	1.71 (1.25–2.34)	.001
Males	325/354	288/357	1.12 (0.90–1.40)	.319
Smoking Status
Yes	134/148	88/105	1.13 (0.77–1.65)	.545
No	359/359	342/465	1.35 (1.10–1.65)	.005
Drinking Status
Yes	95/116	63/73	0.95 (0.61–1.50)	.834
No	398/391	367/497	1.37 (1.13–1.67)	.002
Residence
Rural	296/305	217/285	1.25 (0.98–1.60)	.068
Urban	197/202	213/285	1.34 (1.03–1.76)	.033
FH
Yes	27/29	6/6	0.93 (0.24–3.64)	.917
No	466/478	424/564	1.30 (1.08–1.56)	.005

OR: odds ratio; CI: confidence interval; FH: family history of GC.

^a Adjusted for age, sex, smoking status, drinking status, residence, hypertension, diabetes, and FH of GC (excluding the stratified factor in each stratum) in logistic regression model.

The significant results are in bold.

Table 4. Associations between variant TP73-AS1 genotypes and clinicopathologic characteristics of gastric cancer (rs3737589).

Variable	AG + GG, AA for rs3737589		Logistic regression for rs3737589
	AG + GG, n	AA, n	Adjusted OR (95%CI)^a	p
Tumor differentiation
Well	33	30	1
Moderate	247	249	0.90 (0.53–1.54)	.704
Poor	213	228	0.83 (0.49–1.42)	.502
Depth of tumor infiltration
T1 + T2	159	198	1
T3 + T4	334	309	1.36 (1.04–1.77)	.023
Lymph node metastasis
Negative	181	186	1
Positive	312	322	1.01 (0.78–1.30)	.972
Localization
Cardia	235	234	1
Noncardia	258	273	0.94 (0.73–1.21)	.628

OR: odds ratio; CI: confidence interval.

^a Adjusted for age, sex, smoking status, drinking status, residence, hypertension, diabetes, and FH of GC in logistic regression model.

The significant results are in bold.

Figure 1. the RNAfold algorithm in silico predicting the impact of rs1181865 (A) and rs3737589 (B) on the local secondary structure of TP73-AS1.

Figure 2. The effect of rs3737589 on TP73-AS1 expression level. (A): The genotype of rs3737589 and expression of TP73-AS1 gene in stomach was based on the public GTEx portal database. (B): TP73-AS1 levels were determined by qRT-PCR in GC tissues in subjects with the AA (n = 40), AG (n = 35) or GG (n = 5) genotype of rs3737589. Results were shown as mean ± standard error relative to GAPDH levels.

Figure 3. Kaplan-Meier survival curves for the overall survival by characteristics and clinical features of gastric cancer patients. (age, sex, sites, depth of invasion, lymph nodes metastasis.).

Figure 4. Kaplan-Meier survival curves of rs3737589 polymorphism for the overall survival in patients with gastric cancer. (AA vs. AG, AA vs. GG, AA vs. AG + GG.).

Table 5. Survival analysis by clinicopathologic features of gastric cancer patients.

Variables	Patients	Deaths	MST (months)	Log-rank p	HR (95%CI)	p*
Overall	369	73
Age (years)
≤60	155	24	74.3		1
>60	214	49	66.5	.105	1.49 (0.92–2.43)	.109
Sex
Male	262	49	69.0		1
Female	107	24	69.8	.489	1.19 (0.73–1.94)	.491
Sites
Cardia	178	36	64.1		1
Non-cardia	191	37	71.9	.769	0.93 (0.59–1.48)	.770
Depth of invasion
T1 + T2	130	2	83.8		1
T3 + T4	239	71	62.4	<.001	21.76 (5.34–88.72)	<.001
Lymph nodes metastasis
Negative	152	11	76.5		1
Positive	217	62	65.3	<.001	4.60 (2.42–8.74)	<.001

MST: mean survival time; HR: hazard ratio; CI: confidence interval.

P* was calculated by Univariate Cox regression analysis.

The significant results are in bold.

Table 6. Association between genotype of rs3737589 and overall survival in gastric cancer patients.

genotype	Patients/Deaths	MST (months)	Log-rank p	Univariate		Multivariate
				HR (95%CI)	p	HR (95%CI)^a	p
rs3737589
AA	199/30	74.8		1		1
AG	153/37	54.7	.030	1.69 (1.05–2.74)	.032	1.62 (1.00–2.62)	.051
GG	17/6	47.5	.016	2.79 (1.16–6.71)	.022	2.77 (1.12–6.87)	.028
AG + GG	170/43	54.0	.013	1.79 (1.13–2.86)	.014	1.72 (1.08–2.75)	.023

MST: mean survival time; HR: hazard ratio; CI: confidence interval.

^a Adjusted for depth of invasion, lymph nodes metastasis in Cox regression multivariate analysis.

The significant results are in bold.