ASSOCIATION OF IL-8 -251T&gt;A (RS4073) POLYMORPHISM WITH SUSCEPTIBILITY TO GASTRIC CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS BASED ON 33 CASE-CONTROL STUDIES

MOGHIMI, Mansour; DASTGHEIB, Seyed Alireza; HEIRANIZADEH, Naeimeh; ZARE, Mohammad; SHEIKHPOUR, Elnaz; NEAMATZADEH, Hossein

doi:10.1590/S0004-2803.202000000-16

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REVIEW • Arq. Gastroenterol. 57 (01) • Jan-Mar 2020 • https://doi.org/10.1590/S0004-2803.202000000-16 copy

ASSOCIATION OF IL-8 -251T>A (RS4073) POLYMORPHISM WITH SUSCEPTIBILITY TO GASTRIC CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS BASED ON 33 CASE-CONTROL STUDIES

Associação de polimorfismo IL-8 -251T>A (rs4073) com suscetibilidade ao câncer gástrico: uma revisão sistemática e meta-análise com base em 33 estudos caso controle

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

BACKGROUND:

The role of -251A>T polymorphism in the anti-inflammatory cytokine interleukin-8 (IL-8) gene in gastric cancer was intensively evaluated, but the results of these studies were inconsistent.

OBJECTIVE:

Therefore, we performed a meta-analysis to provide a comprehensive data on the association of IL-8 -251T>A polymorphism with gastric cancer.

METHODS:

All eligible studies were identified in PubMed, Web of Science, EMBASE, Wanfang and CNKI databases before September 01, 2019. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were derived from a fixed effect or random effect model.

RESULTS:

A total of 33 case-control studies with 6,192 cases and 9,567 controls were selected. Overall, pooled data showed that IL-8 -251T>A polymorphism was significantly associated with an increased risk of gastric cancer under all five genetic models, i.e., allele (A vs T: OR=1.189, 95% CI 1.027-1.378, P=0.021), homozygote (AA vs TT: OR=1.307, 95% CI 1.111-1.536, P=0.001), heterozygote (AT vs TT: OR=1.188, 95% CI 1.061-1.330, P=0.003), dominant (AA+AT vs TT: OR=1.337, 95% CI 1.115-1.602, P=0.002) and recessive (AA vs AT+TT: OR=1.241, 95% CI 1.045-1.474, P=0.014). The stratified analysis by ethnicity revealed an increased risk of gastric cancer in Asians and mixed populations, but not in Caucasians. Moreover, stratified by country found a significant association in Chinese, Korean and Brazilian, but not among Japanese.

CONCLUSION:

This meta-analysis suggests that the IL-8 -251T>A polymorphism is associated with an increased risk of gastric cancer, especially by ethnicity (Asian and mixed populations) and country (Chinese, Korean and Brazilian).

HEADINGS:
Stomach neoplasms; Interleukin 8; Genetic polymorphism; Meta-analysis

First author	Country (Ethnicity)	Genotyping Method	SOC	Case/Control	Cases					Controls					MAFs	HWE	NOS
					Genotypes			Allele		Genotypes			Allele
					TT	TA	AA	T	A	TT	TA	AA	T	A
Savage 2004	USA (Caucasian)	SBE	PB	88/429	26	39	23	91	85	147	207	75	501	357	0.416	0.884	7
Savage 2004	USA (Caucasian)	TaqMan	PB	287/428	76	140	71	282	292	117	205	106	439	417	0.487	0.391	7
Lee 2005	Taiwan (Asian)	PCR-RFLP	HB	364/291	156	164	44	609	331	108	127	56	354	262	0.411	0.093	8
Taguchi 2005	Japan (Asian)	PCR-RFLP	HB	396/215	161	191	44	513	279	125	105	22	355	149	0.296	0.994	7
Lu 2005	China (Asian)	PCR-DHPLC	PB	250/300	94	102	54	290	210	119	144	37	382	218	0.363	0.515	8
Zeng 2005	China (Asian)	PCR-RDB	PB	206/504	37	110	59	184	228	43	114	39	200	192	0.490	0.021	8
Leung 2006	China (Asian)	TaqMan	NS	123/179	44	56	23	144	102	51	92	36	194	164	0.467	0.835	7
Ohyauchi 2005	Japan (Asian)	DS	HB	212/244	93	106	13	292	132	149	84	11	534	158	0.217	0.847	7
Shirai 2005	Japan (Asian)	PCR-RFLP	HB	181/468	83	78	20	244	118	211	208	49	630	306	0.327	0.830	7
Kamali-Sarvestani 2006	Iran (Asian)	ASO-PCR	HB	19/153	4	6	9	14	24	57	74	22	188	118	0.386	0.797	7
Kamangar 2006	Finland (Caucasian)	TaqMan	PB	112/207	42	56	14	140	84	72	111	24	255	159	0.384	0.054	8
Garza-Gonzalez 2007	Mexico (Mixed)	ARMS-PCR	HB	78/189	15	47	16	77	79	69	87	33	225	153	0.405	0.538	7
Crusius 2008	France (Caucasian)	Real-Time	PB	236/1139	75	113	48	263	209	315	574	250	1204	1074	0.471	0.705	8
Canedo 2008	Portugal (Caucasian)	TaqMan	PB	333/693	111	169	53	391	275	203	353	137	759	627	0.452	0.459	7
Szoke 2008	Hungary (Caucasian)	ARMS-PCR	NS	35/168	11	15	9	37	33	38	93	37	169	167	0.497	0.164	7
Kang 2009	Korea (Asian)	PCR-RFLP	PB	334/322	126	159	49	411	257	147	148	27	442	202	0.314	0.225	8
Ko 2009	Korea (Asian)	Snapshot	PB	81/308	34	35	12	103	59	135	146	27	416	200	0.325	0.155	8
Ye 2009	Korea (Asian)	PCR-RFLP	HB	153/206	54	82	17	190	116	97	86	23	280	132	0.320	0.552	7
Song 2009	China (Asian)	PCR-RFLP	HB	125/140	33	72	20	138	112	47	70	23	164	116	0.414	0.720	8
Liu 2009	China (Asian)	TaqMan	HB	138/137	26	89	23	141	135	50	72	15	172	102	0.372	0.145	7
Li 2010	China (Asian)	PCR-DHPLC	NS	101/137	25	65	11	115	87	59	64	14	184	92	0.336	0.579	7
Bo 2010	China (Asian)	PCR-RFLP	HB	208/190	64	108	36	236	180	68	96	26	232	148	0.386	0.389	8
Zhang 2010	China (Asian)	PCR-RFLP	PB	519/504	130	261	128	521	517	160	251	93	571	437	0.434	0.754	8
Vinagre 2011	Brazil (Mixed)	PCR-RFLP	HB	102/103	21	56	25	98	106	42	42	19	126	80	0.387	0.122	8
Felipe 2012	Brazil (Mixed)	PCR-RFLP	PB	104/196	31	58	15	120	88	59	85	52	203	189	0.482	0.065	7
Burada 2012	Romania (Caucasian)	Real-Time	HB	105/242	31	54	20	116	94	82	112	48	276	208	0.430	0.385	7
Pan 2014	China (Asian)	SBE	HB	308/308	92	168	48	352	264	101	148	59	350	266	0.432	0.715	7
Qadri 2014	India (Asian)	PCR-CTPP	PB	130/200	50	68	12	168	92	94	94	12	282	118	0.295	0.066	8
Kumar 2015	India (Asian)	ASO-PCR	HB	200/250	67	86	47	220	180	93	122	35	308	192	0.384	0.618	8
de Oliveira 2015	Brazil (Mixed)	PCR-RFLP	HB	240/207	61	134	45	222	192	62	98	47	256	224	0.464	0.488	7
Wang 2016	China (Asian)	MassARRAY	HB	132/296	47	59	26	153	111	102	144	50	348	244	0.412	0.945	7
Ramis 2017	Brazil (Mixed)	PCR-RFLP	PB	9/38	4	1	4	9	9	11	20	7	42	34	0.447	0.691	7
Chang 2017	Korea (Asian)	PCR-RFLP	HB	283/176	81	168	34	330	236	70	89	17	229	123	0.349	0.136	8

Subgroup	Genetic model	Type of model	Heterogeneity		Odds ratio				Publication bias
Subgroup	Genetic model	Type of model	I² (%)	P_H	OR	95% CI	Z_test	P_OR	P_Beggs	P_Eggers
Overall	A vs T	Random	87.85	≤0.001	1.189	1.027-1.378	2.312	0.021	0.245	0.926
	AA vs TT	Random	55.20	≤0.001	1.307	1.111-1.536	3.239	0.001	0.117	0.029
	AT vs TT	Random	50.86	≤0.001	1.188	1.061-1.330	2.987	0.003	0.258	0.528
	AA+AT vs TT	Random	83.25	0.020	1.337	1.115-1.602	3.141	0.002	0.060	0.228
	AA vs AT+TT	Random	69.17	≤0.001	1.241	1.045-1.474	2.457	0.014	0.141	0.233
Ethnicity
Asians	A vs T	Random	89.49	≤0.001	1.299	1.068-1.580	2.614	0.009	0.650	0.520
	AA vs TT	Random	51.39	0.004	1.458	1.200-1.771	3.800	≤0.001	0.319	0.140
	AT vs TT	Random	45.31	0.013	1.222	1.076-1.388	3.089	0.002	0.607	0.574
	AA+AT vs TT	Random	86.93	≤0.001	1.470	1.151-1.878	3.088	0.002	0.074	0.262
	AA vs AT+TT	Random	72.40	≤0.001	1.394	1.106-1.756	2.819	0.005	0.927	0.755
Caucasians	A vs T	Fixed	19.86	0.278	0.972	0.883-1.070	-0.579	0.562	0.763	0.366
	AA vs TT	Fixed	10.68	0.348	0.927	0.762-1.127	-0.759	0.448	0.763	0.310
	AT vs TT	Fixed	0.00	0.654	0.925	0.791-1.080	-0.987	0.323	1.000	0.962
	AA+AT vs TT	Fixed	0.00	0.530	0.924	0.797-1.070	-1.062	0.288	0.367	0.627
	AA vs AT+TT	Fixed	3.701	0.398	0.974	0.822-1.154	-0.300	0.764	0.367	0.196
Mixed	A vs T	Random	86.72	≤0.001	1.044	0.642-1.696	0.173	0.862	0.220	0.391
	AA vs TT	Random	64.18	0.025	1.310	0.715-2.401	0.874	0.382	0.806	0.565
	AT vs TT	Fixed	56.82	0.055	1.639	1.244-2.153	3.518	≤0.001	0.806	0.528
	AA+AT vs TT	Random	58.36	0.048	1.526	0.990-2.352	1.913	0.056	0.806	0.919
	AA vs AT+TT	Random	60.55	0.038	0.984	0.601-1.611	-0.064	0.949	0.086	0.271
Country
Chinese	A vs T	Random	93.30	≤0.001	1.390	0.999-1.933	1.954	0.051	0.591	0.905
	AA vs TT	Fixed	36.37	0.117	1.427	1.194-1.704	3.921	≤0.001	1.000	0.966
	AT vs TT	Random	54.56	0.019	1.225	0.993-1.510	1.898	0.058	0.474	0.463
	AA+AT vs TT	Random	92.61	≤0.001	1.701	1.051-2.752	2.163	0.031	0.591	0.556
	AA vs AT+TT	Random	78.97	≤0.001	1.409	0.993-2.000	1.918	0.055	0.720	0.657
Korean	A vs T	Fixed	0.00	0.936	1.315	1.143-1.514	3.816	≤0.001	0.089	0.035
	AA vs TT	Fixed	0.00	0.782	1.773	1.282-2.452	3.462	0.001	0.734	0.270
	AT vs TT	Fixed	0.00	0.391	1.263	1.026-1.554	2.200	0.028	0.734	0.794
	AA+AT vs TT	Fixed	0.00	0.547	1.438	1.182-1.749	3.639	≤0.001	0.734	0.761
	AA vs AT+TT	Fixed	0.00	0.429	1.488	1.098-2.016	2.561	0.010	0.734	0.534
Brazilian	A vs T	Random	86.03	≤0.001	0.943	0.547-1.626	-0.212	0.832	0.308	0.481
	AA vs TT	Random	64.91	0.036	1.142	0.573-2.276	0.377	0.706	0.734	0.704
	AT vs TT	Fixed	56.82	0.055	1.636	1.244-2.153	3.518	≤0.001	0.734	0.474
	AA+AT vs TT	Fixed	57.09	0.072	1.360	1.026-1.803	2.138	0.033	0.734	0.789
	AA vs AT+TT	Random	67.23	0.027	0.949	0.511-1.764	-0.165	0.869	0.308	0.392
Japanese	A vs T	Random	92.09	≤0.001	0.549	0.229-1.317	-1.344	0.179	0.296	0.007
	AA vs TT	Fixed	0.00	0.440	1.374	0.955-1.977	1.710	0.087	1.000	0.597
	AT vs TT	Random	74.20	0.021	1.391	0.923-2.096	1.578	0.115	1.000	0.775
	AA+AT vs TT	Random	79.38	0.008	1.246	0.796-1.948	0.962	0.336	1.000	0.152
	AA vs AT+TT	Fixed	0.00	0.864	1.129	0.796-1.601	0.679	0.497	0.122	1.000
Source of controls
HB	A vs T	Random	81.06	≤0.001	1.139	0.959-1.351	1.484	0.138	0.111	0.901
	AA vs TT	Random	53.23	0.004	1.402	1.117-1.760	2.913	0.004	0.002	0.001
	AT vs TT	Random	49.95	0.010	1.346	1.150-1.576	3.693	≤0.001	0.063	0.103
	AA+AT vs TT	Random	67.52	≤0.001	1.397	1.158-1.684	3.496	≤0.001	0.007	0.003
	AA vs AT+TT	Random	48.38	0.013	1.135	0.933-1.380	1.264	0.206	0.015	0.002
PB	A vs T	Random	92.79	≤0.001	1.255	0.958-1.645	1.652	0.099	1.000	0.814
	AA vs TT	Random	62.35	0.001	1.277	0.989-1.648	1.875	0.061	0.951	0.530
	AT vs TT	Fixed	5.38	0.393	1.040	0.930-1.162	0.684	0.494	0.760	0.345
	AA+AT vs TT	Random	90.77	≤0.001	1.278	0.896-1.824	1.355	0.175	0.951	0.846
	AA vs AT+TT	Random	82.21	≤0.001	1.407	1.020-1.941	2.079	0.038	0.951	0.481
Genotyping methods
PCR-RFLP	A vs T	Random	82.90	≤0.001	1.081	0.881-1.327	0.747	0.455	0.427	0.154
	AA vs TT	Random	60.54	0.002	1.271	0.970-1.665	1.740	0.082	1.000	0.968
	AT vs TT	Fixed	31.91	0.123	1.248	1.113-1.400	3.797	0.001	0.360	0.988
	AA+AT vs TT	Random	49.25	0.023	1.250	1.065-1.467	2.732	0.006	0.669	0.681
	AA vs AT+TT	Random	58.77	0.004	1.070	0.843-1.358	0.558	0.577	0.760	0.986
TaqMan	A vs T	Random	67.36	0.016	1.025	0.831-1.264	0.227	0.821	0.220	0.488
	AA vs TT	Random	61.83	0.033	1.024	0.678-1.546	0.111	0.911	0.220	0.304
	AT vs TT	Random	66.24	0.019	1.032	0.741-1.437	0.187	0.852	0.806	0.525
	AA+AT vs TT	Random	84.10	≤0.001	1.140	0.715-1.816	0.549	0.583	0.462	0.293
	AA vs AT+TT	Fixed	0.00	0.413	0.947	0.771-1.163	-0.519	0.604	0.462	0.224
Others	A vs T	Random	91.42	≤0.001	1.370	1.049-1.789	2.310	0.021	0.060	0.550
	AA vs TT	Random	41.04	0.049	1.458	1.167-1.822	3.317	0.001	0.488	0.016
	AT vs TT	Random	55.10	0.005	1.181	0.978-1.427	1.725	0.085	0.428	0.583
	AA+AT vs TT	Random	89.22	≤0.001	1.494	1.048-2.131	2.217	0.027	0.234	0.646
	AA vs AT+TT	Random	75.20	≤0.001	1.531	1.134-2.067	2.783	0.005	0.692	0.490

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[1] Corresponding author: Dr. Seyed Alireza Dastgheib. E-mail: dastgheibsa@gmail.com