Population differences concerning TNF-α gene polymorphisms in gastric carcinogenesis based on meta-analysis.

BACKGROUND: Recent meta-analyses have studied population differences concerning interleukin (IL)-1 gene polymorphisms in gastric carcinogenesis. In addition to the IL-1 gene cluster, candidate genes include those encoding the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. The aim of the study was to systematically review the role of TNF-α-238 and TNF-α-308 gene polymorphisms (genotypes G/G, G/A, A/A) in gastric carcinogenesis by meta-analyzing all relevant studies to look for any differences concerning TNF-α gene polymorphisms in gastric carcinogenesis. METHODS: Extensive English language medical literature searches for human studies were performed up to the end of May 2013, using suitable keywords. Pooled estimates [odds ratio (OR) with 95% confidence intervals (CI)] were obtained using the random-effects model. Heterogeneity between studies was evaluated with the Cochran Q test whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the adjusted rank correlation test. RESULTS: In seventeen studies, from various countries, the TNF-α-308 and TNF-α-238 frequencies of genotypes G/G, G/A, A/A were examined in gastric cancer patients and controls. For TNF-α-308 frequency overall, the pooled ORs with 95%CI for genotype G/G, A/A and G/A were 0.837 (0.712-0.982), 1.430 (1.064-1.923) and 1.145 (0.973-1.348) with respective P values 0.029, 0.018 and 0.104. Subgroup analyses showed significant results for genotype G/G only in Asians [OR=0.774 (0.610-0.983), P=0.036]. CONCLUSION: In this meta-analysis there was an overall statistically significant increased cancer risk associated with TNF-α-308 G/G and A/A genotypes. Subgroup analyses showed significant results for genotype G/G in Asians, whereas no such significant results were found for Caucasians and Hispanics.

The relationship of Helicobacter pylori infection and colon neoplasia, on the basis of meta-analysis.

BACKGROUND: Helicobacter pylori is an important causative factor in gastric carcinogenesis. However, its role in extragastric gastrointestinal malignancies, such as colon neoplasia, is controversial. AIM: The aim of this study was to explore the relationship of H. pylori infection with colon neoplasia by meta-analysis of all relevant studies. MATERIALS AND METHODS: Pooled estimates were obtained using fixed or random-effects models as appropriate. Heterogeneity between studies was evaluated using the Cochran Q-test, whereas the likelihood of publication bias was assessed by constructing funnel plots. RESULTS: Among 238 potentially relevant studies, 210 were rejected as unsuitable and 28 studies were finally eligible for meta-analysis, including a total of 33 sets of data (17 on colon cancer and 16 on colon polyps). There was evidence of heterogeneity (I=57.37%); thus, the random-effects model of meta-analysis was chosen, showing pooled odds ratio (OR) equal to 1.41 [95% confidence interval 1.24-1.60, P=0.000]. The subgroup meta-analyses showed a significant relationship between H. pylori and colon cancer as well as colon polyps [OR 1.3 (1.07-1.59), P=0.01 and OR 1.5 (1.26-1.79), P=0.000, respectively]. CONCLUSION: The results of this meta-analysis showed a modest statistically significant relationship of H. pylori infection with both colon cancer and polyps.

Helicobacter pylori infection and gastric histology in first-degree relatives of gastric cancer patients: a meta-analysis.

OBJECTIVES: Helicobacter pylori (H. pylori) is believed to predispose to gastric cancer by inducing the precancerous changes, that is, atrophy and intestinal metaplasia (IM). First-degree relatives of patients with gastric cancer might be at an increased risk of developing gastric cancer. However, this evidence is based on the scattered individual studies. The aim of this study was to examine the risk of first-degree relatives developing gastric cancer, in comparison with controls that have no family history of gastric cancer, by meta-analyzing all relevant studies. METHODS: Extensive English language medical literature searches for human studies were performed up to the end of November 2009, using suitable keywords. Inclusion and exclusion criteria were identified and in eligible studies data on three parameters, that is, H. pylori prevalence, atrophy and IM, were extracted. Pooled estimates (odds ratio with 95% confidence intervals) were obtained using either the fixed or random-effects model as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test, whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the Egger's regression asymmetry test. RESULTS: Out of 155 initially identified studies, 11 studies, from various countries, fulfilling the inclusion criteria, examined the risk of first-degree relatives developing gastric cancer (n=1500) in comparison with controls (n=2638). For H. pylori prevalence, the pooled odds ratio with 95% confidence interval was 1.925 (1.419-2.611) and the test for overall effect Z was 4.211 (P=0.000). The respective values for atrophy and IM were 2.200 (1.266-3.824), Z=2.797, (P=0.005) and 1.982 (1.363-2.881), Z=3.582 (P=0.000) respectively. CONCLUSION: The results of this meta-analysis showed that first-degree relatives of patients with gastric cancer might be at an increased risk of developing gastric cancer, as judged by significantly higher prevalence of H. pylori, gastric atrophy and IM, in comparison with controls. Consequently, H. pylori detection and prophylactic eradication of the infection should be offered to such individuals. However, follow-up studies are required to prove the above.

Cumulative H. pylori eradication rates in clinical practice by adopting first and second-line regimens proposed by the Maastricht III consensus and a third-line empirical regimen.

OBJECTIVES: The European Helicobacter Study Group has recently issued the current concepts in the management of Helicobacter pylori infection (Maastricht III Consensus Report, 2005). The aim of the study was to examine the cumulative H. pylori eradication rates that can be achieved in clinical practice by adopting first and second regimens as proposed by the Maastricht III consensus and a third-line empirical levofloxacin-based regimen. METHODS: H. pylori-positive patients were treated initially with a first-line eradication triple regimen consisting of omeprazole, amoxicillin, and clarithromycin and subsequently with a second-line quadruple regimen consisting of omeprazole, bismuth, metronidazole, and tetracycline. Finally, after two previous H. pylori eradication failures, patients received omeprazole, amoxicillin, and levofloxacin, as a third-line empirical strategy. The success rate was calculated by both intention-to-treat (ITT) and per protocol (PP) analyses. RESULTS: In total, 540 consecutive H. pylori-positive patients received first-line treatment (omeprazole, amoxicillin, and clarithromycin). H. pylori were eradicated in 380 patients and 40 patients were withdrawn (ITT, 70.3%; PP, 76%). The remaining 120 H. pylori-positive patients received second-line treatment (omeprazole, bismuth, metronidazole, and tetracycline). H. pylori were eradicated in 83 patients and 7 patients were withdrawn (ITT, 69.1%; PP, 73.45%). Finally, the remaining 30 H. pylori-positive patients received third-line treatment (omeprazole, amoxicillin, and levofloxacin). H. pylori were eradicated in 21 patients and 0 patients were withdrawn (ITT, 70%; PP, 70%). Thus, out of 540 patients initially included in the study, H. pylori were eradicated in 484 patients, 47 were withdrawn, and only 9 remained positive. These results give 89.6% ITT and 98.1% PP cumulative H. pylori eradication rates. CONCLUSIONS: By adopting first- and second-line regimens, as proposed by the Maastricht III consensus and a third-line levofloxacin-based empirical regimen, high cumulative H. pylori eradication rates can be achieved. Thus, a substantial number of cultures to determine sensitivity to antibiotics can be avoided with beneficial consequences concerning cost.

Risk of colorectal neoplasm in patients with acromegaly: a meta-analysis.

AIM: To examine the risk of colorectal neoplasm in acromegalic patients by meta-analyzing all relevant controlled studies. METHODS: Extensive English language medical literature searches for human studies, up to December 2007, were performed using suitable keywords. Pooled estimates [odds ratio (OR) with 95% confidence intervals (CI)] were obtained using either the fixed or random-effects model as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the adjusted rank correlation test. RESULTS: For hyperplastic polyps the pooled ORs with 95% CI were 3.557 (2.587-4.891) by fixed effects model and 3.703 (2.565-5.347) by random effects model. The Z test values for overall effect were 7.81 and 6.984, respectively (P < 0.0001). For colon adenomas the pooled ORs with 95% CI were 2.486 (1.908-3.238) (fixed effects model) and 2.537 (1.914-3.364) (random effects model). The Z test values were 6.747 and 6.472, respectively (P < 0.0001). For colon cancer the pooled OR with 95% CI was identical for both fixed and random effects model (OR, 4.351; 95% CI, 1.533-12.354; Z = 2.762, P = 0.006]. There was no significant heterogeneity and no publication bias in all the above meta-analyses. CONCLUSION: Acromegaly is associated with an increased risk of colorectal neoplasm.

The long-term impact of Helicobacter pylori eradication on gastric histology: a systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori infection is a crucial factor in the multistep carcinogenic process of gastric cancer. In this process the gastric mucosa evolves through the stages of acute gastritis, chronic gastritis, gastric atrophy (GA), and intestinal metaplasia (IM) before developing gastric adenocarcinoma. AIMS: The main aim of this study was to systematically review the long-term effects of H. pylori eradication on gastric histology (i.e. effects on GA and IM for both antrum and corpus) by meta-analyzing all relevant studies. METHODS: Extensive English-language medical literature searches for human studies were performed through October 2006, using suitable key words. Pooled estimates [odds ratio (OR) with 95% confidence intervals (CI)] were obtained using random-effects model. RESULTS: For antrum GA the pooled OR with 95% CI was 0.554 (0.372-0.825), p=0.004. For corpus GA the pooled OR was 0.209 (0.081-0.538), p<0.001. For antrum IM the pooled OR was 0.795 (0.587-1.078), p=0.14. For corpus IM the pooled OR was 0.891 (0.663-1.253), p=0.506. CONCLUSION: The results showed significant improvement of GA, whereas improvement was not shown for IM.

Relationship between Helicobacter pylori infection and esophageal neoplasia: a meta-analysis.

BACKGROUND & AIMS: Helicobacter pylori is an important causative factor in gastric carcinogenesis. However, its role in extragastric gastrointestinal malignancies, such as esophageal cancer, is controversial. The aim of this study was to explore the relationship of H. pylori infection and H. pylori cagA-positive strain with this malignancy by performing meta-analysis of all relevant studies. METHODS: Extensive MEDLINE English language medical literature searches for human studies were performed through February 2007 with suitable keywords. Pooled estimates were obtained by using fixed or random-effects model as appropriate. Heterogeneity between studies was evaluated with the Cochran Q test, whereas the likelihood of publication bias was assessed by constructing funnel plots. Their symmetry was estimated by the Begg and Mazumdar adjusted rank correlation test. RESULTS: In adenocarcinoma patients there were inverse significant relationships with both the H. pylori prevalence (pooled odds ratio [OR], 0.52; 95% confidence interval [CI], 0.37-0.73; P < .001) and the prevalence of H. pylori cagA-positive strain (pooled OR, 0.51; 95% CI, 0.31-0.82; P = .006). Similarly in patients with Barrett's esophagus there were inverse significant relationships (pooled OR, 0.64; 95% CI, 0.43-0.94; P = .025 and pooled OR, 0.39; 95% CI, 0.21-0.76; P = .005, respectively). In patients with squamous cell carcinoma there were no significant relationships with both H. pylori prevalence (pooled OR, 0.85; 95% CI, 0.55-1.33; P = .48) and the prevalence of H. pylori cagA-positive strains (pooled OR, 1.22; 95% CI, 0.7-2.13; P = .48). CONCLUSIONS: The results showed an inverse statistically significant relationship of H. pylori infection with both esophageal adenocarcinoma and Barrett's esophagus, which might suggest a protective role of the infection in these entities. On the contrary, no statistically significant relationship with squamous cell carcinoma was found.