Association between COX-2 -1195G>A polymorphism and gastrointestinal cancer risk: A meta-analysis

Table 1 Quality evaluation scale of the included literature

Criterion	Score
Representativeness of cases
Selected from population or cancer registry	3
Selected from hospital	2
Selected from pathology archives, but without description	1
Not described	0
Source of controls
Population-based	3
Blood donors or volunteers	2
Hospital-based (cancer-free patients)	1
Not described	0
Case-control match
Matched by age and gender	3
Not matched by age and gender	0
Specimens used for determining genotypes
White blood cells or normal tissues	3
Tumor tissues or exfoliated cells of tissue	0
Hardy-Weinberg equilibrium (HWE)
Hardy-Weinberg equilibrium in control subjects	3
Hardy-Weinberg disequilibrium in control subjects	0
Total sample size
> 1000	3
> 500 and < 1000	2
> 200 and < 500	1
< 200	0

Table 2 Baseline information of the included studies

Ref.	Year	Country	Type of cancer	Source of controls	Matching criteria	Genotypingmethod	Cases			Controls			HWE	Quality score
							AA	AG	GG	AA	AG	GG
Liu et al[27]	2006	China	Gastric cancer	PB	NA	DHPLC	88	116	44	375	771	377	0.626	14
Siezen et al[28]	2006	Netherland	Colorectal cancer	PB	Age, sex, center	PCR-RFLP	127	59	10	243	128	20	0.558	17
Siezen et al[28]	2006	Netherland	Colorectal cancer	PB	Age, sex, center	PCR-RFLP	283	132	19	422	226	41	0.149	18
Jiang et al[29]	2007	China	Gastric cancer	PB	Age, sex	PCR-RFLP	74	132	48	79	163	62	0.187	16
Tan et al[30]	2007	China	Colorectal cancer	PB	Age, sex	PCR-RFLP	320	502	178	308	692	300	0.020	14
Andersen et al[31]	2009	Denmark	Colorectal cancer	PB	Sex	Taqman	230	116	13	482	258	25	0.177	15
Hoff et al[32]	2009	Netherland	Colorectal cancer	HB	Age, sex	PCR-RFLP	213	101	12	232	124	13	0.471	14
Thompson et al[33]	2009	United States	Colorectal cancer	PB	NA	Taqman	275	138	9	297	168	15	0.131	14
Pereira et al[34]	2010	Portugal	Colorectal cancer	HB	NA	PCR-RFLP	70	43	4	177	73	6	0.634	10
Zhang et al[35]	2011	China	Gastric cancer	PB	Age, sex	PCR-RFLP	107	184	32	256	513	175	0.004	14
Zhang et al[36]	2011	China	Gastric cancer	PB	Age, sex	PCR-RFLP	113	175	69	241	527	217	0.027	14
Jing et al[37]	2012	China	Gastric cancer	PB	Age, sex	PCR-RFLP	49	87	19	51	133	53	0.059	15
Li et al[38]	2012	China	Gastric cancer	PB	NA	PCR-RFLP	98	145	53	73	166	80	0.461	14
Shin et al[39]	2012	Korea	Gastric cancer	PB	NA	PCR-RFLP	32	54	14	37	41	22	0.107	12
Zhang et al[40]	2012	China	Colorectal cancer	PB	NA	PCR-RFLP	77	216	50	62	184	94	0.09	12
Andersen et al[41]	2013	Denmark	Colorectal cancer	PB	NA	KASP™ genotyping	587	313	47	1126	560	61	0.397	15
Li et al[42]	2013	China	Colorectal cancer	HB	NA	PCR-RFLP	116	248	87	179	336	114	0.045	9
Makar et al[43]	2013	United States	Colorectal cancer	PB	Age, location, sex	Taqman	910	455	57	1198	509	67	0.162	17
Makar et al[43]	2013	United States	Colorectal cancer	PB	Age, location, sex	Taqman	619	287	33	958	496	63	0.905	17
Makar et al[43]	2013	United States	Colorectal cancer	PB	Age, location, sex	Taqman	376	185	20	509	237	29	0.829	17
Makar et al[43]	2013	United States	Colorectal cancer	PB	Age, location, sex	Taqman	338	138	21	558	249	20	0.206	17
Ruan et al[44]	2013	China	Colorectal cancer	PB	NA	PCR-RFLP	34	67	29	39	53	28	0.232	12
Pereira et al[45]	2014	Portugal	Colorectal cancer	HB	NA	Taqman	143	85	15	323	133	16	0.614	11
Vogel et al[46]	2014	Norseland	Colorectal cancer	PB	NA	KBioscience	110	24	2	209	114	11	0.337	12
Gao et al[47]	2015	China	Gastric cancer	PB	Age, sex	Taqman	86	137	55	74	137	57	0.664	16
Lu et al[17]	2015	China	Gastric cancer	HB	NA	PCR-RFLP	69	39	25	27	35	72	0.000	7
Tao et al[48]	2015	China	Gastric cancer	PB	Age, sex	PCR-RFLP	39	71	26	31	65	25	0.397	15
Zamudio et al[49]	2016	Peru	Gastric cancer	HB	NA	Taqman	85	103	32	106	139	43	0.815	9

HWE: Hardy-Weinberg equilibrium; PB: Population-based; HB: Hospital-based; DHPLC: Denaturing high performance liquid chromatography; PCR-RFLP: Polymerase chain reaction-restriction fragment length polymorphism; NA: Not available.

Table 3 Stratified analyses of the COX-2 -1195G>A polymorphism with risk of gastrointestinal cancers

	n	Allele model			Dominant model			Recessive model			Homozygous comparison			Heterozygous comparison
		(A vs G)			(AA/AG vs GG)			(AA vs GG/AG)			(AA vs GG)			(AG vs GG)
		OR (95%CI)	Ph	FPRP	OR (95%CI)	Ph	FPRP	OR (95%CI)	Ph	FPRP	OR (95%CI)	Ph	FPRP	OR (95% CI)	Ph	FPRP
Total	28	1.15 (1.04, 1.26)1	0.000	0.73	1.24 (1.06, 1.45)1	0	0.876	1.16 (1.04, 1.30)1	0.000	0.914	1.31 (1.08, 1.59)1	0.000	0.873	1.18 (1.04, 1.34)1	0.007	0.915
Type of cancer
Gastric cancer	11	1.35 (1.14, 1.59)1	0.000	0.266	1.54 (1.20, 1.96)1	0.000	0.519	1.43 (1.18, 1.72)1	0.002	0.174	1.80 (1.36, 2.39)1	0.000	0.318	1.35 (1.11, 1.65)1	0.038	0.799
Colorectal cancer	17	1.04 (0.94, 1.15)	0.000	0.998	1.05 (0.87, 1.28)	0.002	0.998	1.04 (0.93, 1.18)	0.000	0.998	1.05 (0.83, 1.32)	0.000	0.999	1.06 (0.90, 1.25)	0.060	0.998
Ethnicity
Asian	14	1.30 (1.14, 1.48)1	0.000	0.069	1.50 (1.23, 1.84)1	0.000	0.167	1.35 (1.14, 1.60)1	0.000	0.376	1.71 (1.33, 2.18)1	0.000	0.093	1.37 (1.15, 1.62)1	0.007	0.213
Caucasian	12	1.00 (0.89, 1.11)	0.000	0.999	0.91 (0.76, 1.08)	0.360	0.996	1.01 (0.89, 1.15)	0.000	0.999	0.91 (0.74, 1.11)	0.186	0.997	0.92 (0.77, 1.09)	0.749	0.997
Mixed	2	1.10 (0.93, 1.31)	0.612	0.997	1.13 (0.74, 1.73)	0.466	0.998	1.13 (0.91, 1.40)	0.781	0.996	1.20 (0.76, 1.88)	0.482	0.998	1.09 (0.69, 1.70)	0.534	0.999
Source of controls
PB	22	1.16 (1.06, 1.25)1	0.000	0.09	1.26 (1.09, 1.45)1	0.003	0.559	1.19 (1.07, 1.33)1	0.000	0.685	1.35 (1.13, 1.61)1	0.000	0.488	1.19 (1.04, 1.36)1	0.031	0.914
HB	6	1.12 (0.75, 1.67)	0.000	0.998	1.14 (0.60, 2.15)	0.000	0.999	1.08 (0.72, 1.63)	0.000	0.999	1.15 (0.54, 2.45)	0.000	0.999	1.12 (0.73, 1.71)	0.021	0.998
Study quality
High (> 9)	23	1.15 (1.06, 1.25)1	0.000	0.504	1.25 (1.09, 1.44)1	0.004	0.667	1.19 (1.07, 1.32)1	0.000	0.502	1.34 (1.12, 1.59)1	0.000	0.469	1.19 (1.04, 1.35)1	0.038	0.873
Low ( ≤ 9)	5	1.13 (0.68, 1.86)	0.000	0.999	1.17 (0.56, 2.45)	0.000	0.999	1.09 (0.65, 1.81)	0.000	0.999	1.17 (0.48, 2.88)	0.000	0.999	1.16 (0.71, 1.90)	0.011	0.998
Genotyping method
PCR-RFLP	16	1.23 (1.08, 1.40)1	0.000	0.633	1.46 (1.19, 1.78)1	0.000	0.231	1.24 (1.06, 1.46)1	0.000	0.909	1.58 (1.23, 2.02)1	0.000	0.436	1.35 (1.14, 1.60)1	0.014	0.376
Taqman	9	0.99 (0.90, 1.08)	0.049	0.999	0.97 (0.82, 1.15)	0.428	0.999	0.99 (0.89, 1.11)	0.063	0.999	0.97 (0.79, 1.19)	0.268	0.999	0.98 (0.82, 1.17)	0.669	0.999
Other technologies	3	1.36 (0.86, 2.17)	0.000	0.997	1.16 (0.58, 2.31)	0.008	0.999	1.52 (0.84, 2.75)	0.000	0.997	1.40 (0.55, 3.53)	0.000	0.999	0.99 (0.62, 1.57)	0.118	0.999

¹OR with statistical significance. n: Number of studies included; Ph: P value for heterogeneity; FPRP: False positive report probability.