Helicobacter pylori infection and esophageal cancer risk: An updated meta-analysis

Table 1 Characteristics of literatures included in the meta-analysis

Ref.	Study area	Year	Study type	HP Dm	Hp+definition1	ESCC				EAC				Matched/adjusted3	Control
						Case		Control		Case		Control
						Hp+	CagA+	Hp+	CagA+	Hp+	CagA+	Hp+	CagA+
Murphy et al[7]	Finnish	2012	Pop	S	HpSe+	64/82	35/82	63/82	36/82	-	-	-	-	Yes/yes	Matched with age, smoking and Alcohol consumption, and date of blood draw to controls, all of cases and controls were male smokers
Khoshbaten et al[9]	Iran	2011	Pop	S	HpSe+	58/100	28/100	83/100	36/100	-	-	-	-	Yes/no	Sex-matched and age-matched health individuals, any clinical evidence of gastrointestinal symptoms were excluded
Venerito et al[8]	Germany	2011	Clin	S, H, U	His+, HpSe+, CagA+ or U+	53/75	42/75	53/75	40/75	-	-	-	-	Yes/no	Sex and age-matched individuals with upper GI symptoms but no malignancy of the upper GI tract
Whiteman et al[11]	Australia	2010	Pop	S	HpSe+	54/208	-	302/1316	-	35/260	-	302/1316	-	Yes/yes	Randomly selected from the same areas, matched to each stratum of age and state
Cook et al[10]	Finnish	2010	Pop	S	HpSe+	64/78	35/78	71/91	42/91	-	-	-	-	Yes/yes	Matched to case for age, years of smoking, cigarettes per day, or body mass index
Wu et al[5]	Taiwan	2009	Pop	S	HpSe+	112/317	91/317	563/1103	268/700	-	-	-	-	No/yes	One part of control is matched by gender and age, but another part wasn't matched
Hu et al[6]	Taiwan	2009	Pop	S	HpSe+	66/180	-	102/194	-	-	-	-	-	Yes/yes	Healthy and cancer-free individuals, matched to age, sex and ethnicity
Früh et al[12]	Canada	2008	Clin	S	CagA + or VacA+	-	-	-	-	36/100	29/100	43/101	30/101	Yes/yes	Healthy GRERD-free, non-blood-related family member and friends of other cancer/surgical patients
Derakhshan et al[24]	Iran	2008	Clin	S	HpSe+	-	-	-	-	9/19	-	28/38	-	Yes/yes	Dyspeptic patients with no peptic ulcer or tumor in their endoscopy
Anderson et al[25]	Ireland	2008	Pop	S	HpSe+	-	-	-	-	55/123	57/123	157/253	150/253	Yes/yes	Randomly selected population-based controls, frequency matched to EAC cases for age and sex
Löfdahl et al[23]	Sweden	2008	Pop	S	HpSe+ or CagA+	-	-	-	-	130/230	-	304/499	-	Yes/no	Random selected from the population register, frequency matched for age and sex
Anandasabapathy et al[26]	United States	2007	Clin	H	His+	-	-	-	-	4/25	-	10/30	-	No/no	Barrett’s patients with no dysplasia
Iijima et al[27]	Japan	2007	Clin	S, H, U	HpSe+, His+ or U+	60/73	-	56/73	-	-	-	-	-	Yes/yes	Endoscoped patients with no localized lesion, matched to cases for age and sex
Kamangar et al[14]	China	2007	Pop	S	HpSe+	231/335	178/335	662/992	552/992	-	-	-	-	No/yes	Randomly selected from the entire baseline participants in the stdy cohort
Simán et al[13]	Sweden	2007	Pop	S	HpSe+	15/37	24/37	68/129	82/129	4/12	6/12	24/47	32/47	Yes/yes	Randomly selected from the study cohorted, matched with age, sex, and date enrollment
Wang et al[28]	China	2006	Pop	S	HpSe+	?/107	-	?/107	-	-	-	-	-	Yes/yes	Neighborhood controls, randomly selected, and matched to cases for age and gender
Wu et al[15]	Taiwan	2005	Pop	S	HpSe+	28/127	-	74/171	-	-	-	-	-	No/yes	Randomly selected from the same community
de Martel et al[29]	United States	2005	Pop	S	HpSe+	-	-	-	-	19/51	9/18	74/150	44/71	Yes/yes	Randomly selected from the study cohorted, matched with age, sex, and date enrollment race, and study site
Ye et al[16]	Sweden	2004	Pop	S	HpSe+	32/85	63/85	198/499	293/499	18/97	42/97	198/499	293/499	Yes/yes	Randomly selected population-based controls, frequency matched to EAC cases for age and sex
2Wang et al[30]	China	2003	Pop	S	HpSe+	33/63	-	145/310	-	-	-	-	-	Yes/no	Healthy subjects with no difference in age and gender
Wu et al[22]	United States	2003	Pop	S	HpSe+	-	-	-	-	49/80	18/80	230/356	106/356	Yes/yes	Matched to cases for age, sex, neighborhood of residence, and race
El Omar et al[21]	United States	2003	Pop	S	HpSe+	31/53	7/26	84/210	46/224	35/108	5/68	84/210	46/224	Yes/no	Matched to cases for age, sex, and study center
Weston et al[20]	United States	2000	Clin	H	His+	-	-	-	-	3/20	-	96/217	-	No/no	Patients with GERD symptoms but no Barrett’s esophagus
Vieth et al[19]	Germany	2000	Clin	H	His+	-	-	-	-	66/138	-	468/712	-	No/no	Patients with non-ulcer dyspepsia and no endoscopic signs of GERD
Peek et al[18]	United States	1999	Clin	S, H	HpSe+ or His+	-	-	-	-	11/30	3/30	20/48	25/48	No/no	Patients endoscoped for reasons other Than GERD or Barrett’s
Oberg et al[31]	United States	1999	Clin	H	His+	-	-	-	-	5/37	-	32/229	-	No/no	Patients with foregut symptoms and benign diseases
Talley et al[17]	United States	1991	Clin	S	HpSe+	20/41	-	96/252	-	-	-	-	-	No/no	Asymptomatic volunteers and patients with benign esophageal, lung, or culoskeletal disorders

¹Helicobacter pylori (H. pylori) positivity definition;

²Because the article showed that there was no difference in age and gender between cases and health controls, this study was analyzed as a matched population study;

³Individual-matching of controls to cases for age and gender/reporting adjusted ORs for the association between H. pylori and cancer. Clin: Clinical based; Pop: Population based; NR: Not reported; Hp Dm: Hpdetection method; S: Serology; H: Histology; U: Rapid urease test; His⁺: Positive histological examination of tissue samples; HpSe⁺: Sero-positivity for antibodies to whole-cell; VacA⁺: Sero-positivity for antibodies to VacA; CagA⁺: Sero-positivity for antibodies to cytotoxin-associated gene-A; U⁺: Positive rapid urease test; GERD: Gastroesophageal reflux disease; ESCC: Esophageal squamous cell carcinoma; EAC: Esophageal adenocarcinoma; GI: Gastrointestinal.

Table 2 Meta-analysis of the Helicobacter pylori infection on the risk of esophageal squamous cell carcinoma and esophageal adenocarcinoma

	Studies	P1	I2,2	Overall OR (95%CI)
Esophageal squamous cell carcinoma
Case/control (1961/5704)
All studies	16	< 0.01	74.50%	0.83 (0.63, 1.03)
Population-based studies	14	< 0.01	76.00%	0.79 (0.59, 1.00)
Clinical-based studies	2	0.86	< 0.01	1.49 (0.66, 2.31)
Eastern studies	8	< 0.01	79.50%	0.66 (0.43, 0.89)
Western studies	8	0.42	1.20%	1.02 (0.80, 1.25)3
Studies with matched controls	11	< 0.01	71.80%	0.90 (0.61, 1.20)
Studies without matched controls	5	< 0.01	82.90%	0.79 (0.46, 1.12)
Hp+ only definition as HpSe+	14	< 0.01	76.80%	0.81 (0.60, 1.02)
Adjusted results	11	< 0.01	80.50%	0.84 (0.56, 1.12)
CagA+vs Hp-	9	0.03	52.00%	0.97 (0.76, 1.24)
Eastern study	3	0.22	35.00%	0.77 (0.65, 0.92)3
Western studies	6	0.39	3.60%	1.26 (0.97, 1.63)3
Esophageal adenocarcinoma
Case/control (1330/4705)
All studies	15	0.131	29.9	0.59 (0.51, 0.68)
Population-based studies	8	0.106	40.9	0.62 (0.52, 0.73)
Clinical-based studies	7	0.319	14.5	0.53 (0.40, 0.68)
Eastern study	1	-	-	-
Western studies	14	0.128	31	0.60 (0.52, 0.68)
Studies with matched controls	10	0.139	33.6	0.62 (0.53, 0.72)
Studies without matched controls	5	0.333	12.7	0.49 (0.36, 0.66)
Hp+ definition as HpSe+	8	0.299	16.6	0.55 (0.45, 0.66)
Hp+ definition as His+	4	0.334	11.7	0.46 (0.33, 0.64)
Adjusted results	8	0.200	28.6	0.51 (0.40, 0.61)
CagA+vs Hp-	8	0.11	39.9	0.56 (0.45, 0.70)
Eastern study	0	-	-	-
Western studies	8	0.11	39.9	0.56 (0.45, 0.70)

¹P value for Q statistical in random effects model; ²Higgins I² statistic for heterogeneity in random effects model;

³The overall value synthesized by fixed effects model. HpSe⁺: Sero-positivity for antibodies to whole-cell; CagA⁺: Sero-positivity for antibodies to cytotoxin-associated gene-A.