Xue FB, Xu YY, Wan Y, Pan BR, Ren J, Fan DM. Association of H. pylori infection with gastric carcinoma: A meta analysis. World J Gastroenterol 2001; 7(6): 801-804 [PMID: 11854905 DOI: 10.3748/wjg.v7.i6.801]
Corresponding Author of This Article
Fu-Bo Xue, Department of Health Statistics, the Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China. alnico@sohu.com
Article-Type of This Article
Original Research
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Fu-Bo Xue, Yong-Yong Xu, Yi Wan, Department of Health Statistics, Gastroenterology of XiJing Hospital, the Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
Bo-Rong Pan, Jun Ren, Department of Oncology, Gastroenterology of XiJing Hospital, the Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
Dai-Ming Fan, Gastroenterology of Xijing Hospital, the Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
ORCID number: $[AuthorORCIDs]
Author contributions: All authors contributed equally to the work.
Supported by Funds for University Key Teachers by the Ministry of Education, No. 2000-65
Correspondence to: Fu-Bo Xue, Department of Health Statistics, the Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China. alnico@sohu.com
Telephone: +86-29-3374853
Received: July 19, 2001 Revised: September 19, 2001 Accepted: October 23, 2001 Published online: December 15, 2001
Abstract
AIM: To follow the principles of evidence based medicine to reach the integrated results of these studies.
METHODS: Twenty-one papers of case-control studies were selected, including 11 on gastric cancer, 7 on precancerous lesion of stomach and 3 on lymphoma of stomach. Meta analysis was used to sum up the odds ratios (OR) of these studies.
RESULTS: H. pylori vsgastric cancer (intestinal and diffuse type): the odds ratio from the fixed effect model is 3.0016 (95% CI: 2.4197-3.7234, P < 0.001). H. pylori vs precancerous lesion of stomach: a random effect model was used to calculate the summary odds ratio and its value is 2.5635 (95% CI: 1.8477-3.5566, P < 0.01). H. pylori vs lymphoma of stomach: though the quantity of literature is too small to make Meta analysis, the data of these 3 studies show that lymphoma of stomach is highly associated with H. pylori infections.
CONCLUSION: Since it had been revealed that H. pylori infection pre-exists in gastric carcinoma and precancerous lesions, the results of Meta analysis present a strong evidence to support the conclusion that H. pylori infection is a risk factor for gastric carcinoma.
Citation: Xue FB, Xu YY, Wan Y, Pan BR, Ren J, Fan DM. Association of H. pylori infection with gastric carcinoma: A meta analysis. World J Gastroenterol 2001; 7(6): 801-804
Since H. pylori was founded in 1983, the association of H. pylori with H. pylori related diseases has become the hot spot of gastroenterological studies. Gastric carcinoma is the most important disease among H. pylori related diseases. It is believed that H. pylori is one of the important causes of gastric carcinoma. But there is still lack of the final conclusion and the definite mechanisms of their association.
In China, malignant tumor is the second death cause of men and the third death cause of women according to the investigation of death cause in 29 provinces, municipalities and autonomous regions conducted from 1973 to 1975. The annual average mortality rate of gastric carcinoma is as high as 16 per 10 0 thousand, which is the leading death cause among malignant tumors, and the rates of H. pylori infection are higher than 50 percent in the mainland of China[1]. In the past two decades, Chinese medical researchers and clinical workers have done much a great amount of studies to reveal the relationship and the mechanisms of the association of H. pylori with gastric carcinoma. Most of them agree to the opinion that H. pylori is a risk factor for gastric carcinoma, but a certain number of them hold different points of view[2-19].
Eslick et al[20] have worked out the summary odds ratio of 2.04 of those same studies made in Western countries. In this paper, we reviewed all the literatures of studies in China on the relationship between H. pylori and gastric carcinoma as well as precancerous lesions of stomach published from 1995 in order to reach a summary conclusion using statistical methods.
MATERIALS AND METHODS
Literature
A CBM (Chinese Biomedical Database) search for articles published from 1995 was performed with the MeSH headings “Helicobacter pylori,”“gastric carcinoma (cancer),”“precancerous lesion of stomach” and “lymphoma of stomach.” More than 100 papers were retrieved. Since most of them had no appropriate controls or their data did not meet the requirements of Meta analysis, only 21 papers of case-control studies were selected, including 11 about gastric cancer (Table 1), 7 on precancerous lesions of stomach (Table 2) and 3 on lymphoma of stomach (Table 3).
Table 1 Eleven case-control studies of H. pylori vs. gastric cancer[21-31].
No.
Cases
Controls
OR
95%CI
χ²
P value
Hp (+)
Hp (-)
Hp (+)
Hp (-)
1
61
13
49
25
2.394
1.110～5.163
4.284
0.038
2
13
3
78
68
3.778
1.033～13.818
3.475
0.062
3
71
21
46
46
3.381
1.791～6.384
13.52
0.000
4
99
23
6
8
5.793
1.841～18.155
8.400
0.004
5
35
16
34
87
5.597
2.746～11.408
22.873
0.000
6
101
35
6236
4628
2.142
1.455～3.151
14.959
0.000
7*
16
9
32
43
2.389
0.937～6.092
2.618
0.106
8*
21
19
3
12
4.421
1.080～18.093
3.457
0.063
9*
55
21
12
10
2.183
0.821～5.805
1.75
0.186
10
90
13
89
50
3.889
1.977～7.653
15.500
0.000
11
60
25
35
50
3.429
1.815～6.475
13.743
0.000
Summary
622
198
6620
5027
3.0016
2.4197～3.7234
99.9483
0.000
Table 2 Seven case-control studies of H. pylori vs. precancerous lesion of stomach[32-38].
No.
Cases
Controls
OR
95%CI
χ²
P value
Hp (+)
Hp (-)
Hp (+)
Hp (-)
1
344
194
1467
1311
1.585
1.309～1.918
22.089
0.000
2
67
29
175
180
2.376
1.466～3.851
11.955
0.000
3
103
38
26
53
5.525
3.036～10.056
31.988
0.000
4
427
252
992
892
1.524
1.273～1.824
20.736
0.000
5
99
41
12
28
5.634
2.614～12.144
20.128
0.000
6
134
35
272
201
2.829
1.870～4.282
24.490
0.000
7
188
27
332
135
2.831
1.805～4.442
20.836
0.000
Summary
1362
616
3276
2800
2.5635
1.8477～3.5566
31.7540
0.000
Table 3 Three case-control studies of H. pylori vs. lymphoma of stomach[39-41].
No.
Cases
Controls
OR
95%CI
χ²
P value
Hp (+)
Hp (-)
Hp (+)
Hp (-)
1
24
5
13
16
5.908
1.762～19.810
7.465
0.006
2
15
0
36
24
10.811
1.347～86.798
5.692
0.017
3
34
5
31
23
5.045
1.709～14.896
8.176
0.004
Data
Eleven case-control studies on the relationship between H. pylori infection and gastric cancer (intestinal and diffuse type) included totally 820 patients and 11-647 controls. Among them, 7 attained significant results, and 4 did not (Table 1).
Seven case-control studies on the relationship between H. pylori infection and precancerous lesions of stomach included totally 1978 patients and 6076 controls. All of them had significant results (Table 2).
Three case-control studies on the relationship between H. pylori infection and lymphoma of the stomach included totally 83 patients and 143 controls. All of them had significant results (Table 3).
Methods
In the statistical analysis, Meta analysis method with fixed effect model and random effect model was used to reach the integrated conclusion[42].
RESULTS
H. pylori infection vs gastric cancer
All 11 odds ratios were statistically homogenous (P > 0.05). Summary odds ratio for gastric cancer related to H. pylori infection was 3.0016 using fixed effect model (95% CI 2.41 97-3.7234, Table 1). Figure 1 shows the summary odds ratio and odds ratios and their 95%CI of 11 case-control studies on the relationship between H. pylori infection and gastric cancer.
Figure 1 Odds ratios and summary odds ratio with 95%CI of 11 case-control studies.
H. pylori infection vs precancerous lesion of stomach
Since 7 odds ratios were not statistically homogenous (P < 0.05), random effect model was used to calculate the summary odds ratio. The summary odds ratio for precancerous lesions of stomach related to H. pylori infection was 2.5635 (95% CI 1.8477-3.5566, Table 2). Figure 2 shows the summary odds ratio and odds ratios and their 95%CI of 7 case-control studies on the relationship between H. pylori and precancerous lesions of the stomach.
Figure 2 Odds ratios and summary odds ratio with 95%CI of 7 case-control studies.
H. pylori vs lymphoma of stomach
Though the quantity of literature is too small to make Meta analysis, the data of these 3 studies show that lymphoma of the stomach was highly associated with H. pylori infections. Figure 3 shows the odds ratios and their 95%CI of 3 case-control studies on the relationship between H. pylori infection and lymphoma of the stomach.
Figure 3 Odds ratios with 95%CI of 3 case-control studies.
DISCUSSION
Since it had been revealed that H. pylori infection pre-exists in gastric carcinoma and precancerous lesions, the result of the Meta analysis present a strong evidence to support the conclusion that H. pylori infection is a risk factor for gastric carcinoma.
The following statements might explain the association of H. pylori infection with gastric carcinoma: ① gastric carcinoma is caused by H. pylori infection; ② H. pylori infection is caused by gastric carcinoma; ③ there are some certain factors for H. pylori infection and gastric carcinoma[9]. As we all know that H. pylori infections also exist in the gastric mucosa of nearly normal persons, it is impossible that H. pylori infection is caused by gastric carcinoma. Numerous studies support the point that H. pylori infection exist before the occurrence of gastric carcinoma[43-48], indicating that H. pylori infection is not a secondary infection but a primary infection. It was reported that. Mongolia gerbils have been infected with H. pylori through mouth route, which is implanted in their stomach for a long time. Twenty-six weeks after the infection, severe chronic active gastritis, ulcer and intestinal metaplasia occurred in the stomachs of the gerbils. And 37% of the gerbils involved in the study were attacked with gastric adenocarcinoma 62 wk after the infection[10].
The development and occurrence of gastric carcinoma is a long-lasting process and the effect of multiple factors. It is accepted by numerous scholars that H. pylori is an important risk factor for gastric carcinoma. In addition to the studies that support the association of H. pylori with gastric carcinoma, some researchers investigated the relationship between H. pylori and other kinds of carcinoma such as cancer of the colon, rectum, esophagus etc. and they made a negative conclusion, which proved the effect of H. pylori in gastric carcinoma in the other directions. However, H. pylori is not the unique etiological factor for gastric carcinoma. The association of the occurrence of gastric carcinoma with H. pylori infection should be considered from the angle of the multi-agent compound etiological theory[49-62].
According to the studies that support the opinion of association of H. pylori with gastric carcinoma, It can be assumed that the canceration of gastric mucosa took place under the action of H. pylori in the following process: H. pylori related gastritis of antrum→ atrophic gastritis → intestinal metaplasia → gastric carcinoma.
There are many problems we are going to face. The infection rate of H. pylori is very high in the population surveys. But why most of those with H. pylori infection were not attacked with gastric carcinoma. What are the other factors acting together with H. pylori to cause gastric carcinoma How do they act We must do more prospective interventional trial to answer these questions. It will be more helpful to do random interventional trial of eradication of H. pylori infection among the high-risk groups of gastric carcinoma and precancerous lesions to observe if their incidence rate of gastric carcinoma will decrease. In China, though very few of this kind of prospective studies have been made, an interventional trial of eradication of H. pylori is being made in Shandong and Fujian provinces. It will be of great help in revealing the exact mechanism of H. pylori in the process of gastric mucosa canceration.
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