Helicobacter pylori infection,chronic corpus atrophic gastritis and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: A nested case‐control study

The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case‐control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non‐significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction < 0.01). Our findings provided evidence supporting the null association between H. pylori infection and pancreatic cancer risk in western European populations. However, the suggested association between chronic corpus atrophic gastritis and pancreatic cancer risk warrants independent verification in future studies, and, if confirmed, further studies on the underlying mechanisms.     

Helicobacter pylori seropositivity as a risk factor for pancreatic cancer.

BACKGROUND: Pancreatic cancer is among the most fatal cancers worldwide and one for which few preventable risk factors have been established. Gastric carriage of Helicobacter pylori, particularly cytotoxin-associated gene-A-positive (CagA+) strains, is known to be a risk factor for peptic ulcer disease and gastric cancer and may have a similar etiologic relationship with pancreatic cancer. METHODS: We investigated the association of H. pylori carriage and exocrine pancreatic cancer in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29 133 male Finnish smokers aged 50-69 years at baseline. Case subjects (n = 121) were matched on date of baseline serum collection, study center, age, trial intervention, and completion of the dietary questionnaire to 226 control subjects who were alive at the time the matching case subject was diagnosed and who remained free of cancer, during up to 10 years of follow-up. Levels of immunoglobulin G antibodies to H. pylori whole-cell and CagA+ antigens from stored baseline serum were measured by enzyme-linked immunosorbent assay. Smoking-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression. Statistical tests were two-sided. RESULTS: Seroprevalence of H. pylori was 82% and 73% among case and control subjects, respectively. Compared with seronegative subjects, those with H. pylori or CagA+ strains were at statistically significantly elevated risk of pancreatic cancer (OR = 1.87 [95% CI = 1.05 to 3.34]; OR = 2.01 [95% CI = 1.09 to 3.70], respectively). CONCLUSIONS: Our findings support a possible role for H. pylori carriage in the development of exocrine pancreatic cancer.     

Role of Helicobacter pylori CagA+ strains and risk of adenocarcinoma of the stomach and esophagus

Infection with Helicobacter pylori (H. pylori), especially CagA+ strains, has been associated with an increased risk of noncardia gastric adenocarcinoma. The relationship with junctional cancer (adenocarcinomas of the esophagus and gastric cardia combined) has not been adequately investigated, although some studies have reported a reduced risk associated with H. pylori and CagA seroseropositivity. We investigated this question in a subset of cases and controls from a recently completed, large population-based case-control study of gastric and esophageal adenocarcinomas in Los Angeles County. Using established antigen-specific ELISAs, serum IgG antibodies to H. pylori whole-cell antigens (Helico-G) and CagA were measured in population controls (n = 356) and patients with incident esophageal adenocarcinoma (n = 80), gastric cardia cancer (n = 87) or distal gastric cancers (noncardia gastric adenocarcinoma) (n = 127). After controlling for demographic characteristics (age, gender, race, birthplace, education), smoking and body mass index, seropositivity for H. pylori was associated with a statistically significant increased risk of distal gastric cancer (adjusted odds ratio [OR] = 1.85, 95% confidence interval [CI] = 1.03, 3.32) but the risk of junctional cancer was not increased (adjusted OR = 1.26, 95% CI = 0.82, 1.94). The risk of junctional cancer was not changed when CagA and H. pylori were both considered, but the risk of distal gastric cancer was further increased. Subjects who were seropositive for both CagA and H. pylori compared to those who were seronegative for H. pylori showed a risk of 2.20 (95% CI = 1.13, 4.26) for distal gastric cancer and 0.86 (95% CI = 0.47, 1.59) for junctional cancer. Although tests for interaction between smoking and H. pylori were not statistically significant for junctional or distal gastric cancers, risk for both tumor types tended to be higher among current smokers who were also H. pylori seropositive. In conclusion, we find no evidence that infection with CagA+ strains of H. pylori reduces risk of esophageal and gastric cardia adenocarcinoma in this population. Our findings confirm the positive association between risk of distal gastric cancer and infection with H. pylori infection, especially CagA+ strains.     

Helicobacter pylori infection and development of pancreatic cancer.

BACKGROUND: Infection with Helicobacter pylori is an established risk factor for gastric cancer. Results from two studies suggest that it may also be a risk factor for pancreatic cancer. METHODS: We conducted a nested case control study among 128,992 adult subscribers to the Kaiser Permanente Medical Care Program who had been enrolled in a multiphasic health checkup from 1964 to 1969. Serum collected during the checkup was maintained frozen, and subjects were followed for cancer. Cases consisted of 104 randomly selected subjects among 507 who developed pancreatic cancer in the cohort. Controls consisted of 262 pancreatic cancer-free subjects from a pool of 730 controls previously tested for studies conducted on this cohort. Controls were individually matched to cases on age, gender, race, site, and date of multiphasic health checkup. Control sera were compared with cases for antibodies to H. pylori and the CagA protein. The effects of smoking, alcohol consumption, obesity, and years of education were also investigated. RESULTS: Neither H. pylori [odds ratio (OR), 0.85; 95% confidence interval (95% CI), 0.49-1.48] nor its CagA protein (OR, 0.96; 95% CI, 0.48-1.92) was associated with subsequent development of pancreatic cancer. Smoking (OR, 2.09; 95% CI, 1.17-3.74) and greater number of years of education (OR, 2.13; 95% CI, 1.23-3.69) were risk factors for pancreatic cancer, whereas alcohol consumption and obesity were not. CONCLUSION: Our results suggest that H. pylori infection is not associated with development of pancreatic cancer.     

Association between C1019T polymorphism in the connexin 37 gene and Helicobacter pylori infection in patients with gastric cancer

Objective: To investigate the association between the connexin 37 C1019T polymorphism and Helicobacterpylori infection in patients with gastric cancer. Methods: 388 patients with gastric cancer (GC), 204 with chronicsuperficial gastritis (CSG) were studied. H. pylori was detected by gastric mucosal biopsies biopsy dyeing method.Connexin 37 gene polymorphism 1019 site genotypes were determined by gene sequencing technology. Genotypesand alleles frequencies were compared. Results: (1) Connexin37 gene 1019 site distribution frequency (CC type,TC type, TT type) in the CSG group was 18.1%, 45.1% and 36.8%; in the stomach cancer group it was 35.1%,45.9% and 19.%, conforming to the Hardy-Weinberg euilibrium. (2) In comparison with CSG group, thefrequency of Connexin37 C allele was higher in the gastric cancer group (58.0% vs 40.7%, OR = 2.01, 95%CI =1.58-2.57, P < 0.01). The prevalence of gastric cancer risk was significantly increased in the carriers of C allele(CC+TC) than in TT homozygote (OR = 2.47, 5%CI = 1.68- 3.610. (3) Gastric cancer patients complicated withHp infection 211 cases, gastric cancer group of the male patients with HP positive patients with 187 cases, 40cases of female patients with negative patients, 24 cases were HP positive, negative in 137 cases, control groupmale patients, 28 cases were Hp positive, negative in 95 patients, female patients with Hp positive 6 cases, 75cases were negative. On hierarchical analysis, the male group OR value was 15.9 (95%CI to 9.22-27.3), and thefemale OR was 2.19 (95%CI 0.88-5.59), indicating a greater contribution in males (P <0.01). After eliminationof gender effects, positive HP and gastric cancer were closely related (OR 8.82, 95% CI: 5.45-14.3). (4) Thedistribution frequency of C allele in patients with Hp infection was much higher than that in Hp negative casesin the GC group (64.5% vs 47.0%, OR = 2.05, 95%CI = 1.54-2.74, P < 0.01). Compared with TT homozygotes,(CC+TC) genotype prevalence of gastric cancer risk increased significantly (OR = 2.96, 5%CI = 1.76-2.99 ).Conclusion: The T allele in the connexin37 gene might not only be associated with gastric cancer but also withH. pylori infection.     

Gastric cancer risk in a Mexican population: role of Helicobacter pylori CagA positive infection and polymorphisms in interleukin-1 and -10 genes

Several polymorphisms of the IL1B and IL10 gene promoters have been reported to be associated with gastric cancer risk in Caucasians. However, studies in other populations have shown differing results. We aimed to test for associations between polymorphisms in IL1B (-31 and +3954), IL10-592 and IL1RN variable number of tandem repeats (VNTR) and risk of gastric cancer in a Mexican population. DNA was extracted from sera of 183 gastric adenocarcinoma patients and 377 controls. The IL1B-31, IL1B+3954 and IL10-592 biallelic polymorphisms were discriminated using 5' Nuclease (TaqMan) assays and Pyrosequencing. The IL1RN penta-allelic VNTR polymorphism was genotyped using PCR followed by GeneScan analysis. A significant interaction was found between IL1B-31 and CagA status for the risk of intestinal-type gastric cancer (p = 0.023). Among CagA positive subjects, those with IL1B-31CC genotype had an increased risk of intestinal-type gastric cancer (OR 3.19, 95%CI = 1.05-9.68), compared to carriers of IL1B-31TT genotype. In contrast, among CagA negative subjects, no significant association of IL1B-31CC genotype with gastric cancer was observed. The IL10-592CC genotype was associated with more than doubling of the risk of the intestinal-type gastric cancer (OR, 2.20, 95%CI = 1.04-4.65). A nonsignificantly increased risk for intestinal-type gastric cancer was found in IL1RN*2 carriers (OR 1.49, 95%CI = 0.89-2.50). None of these polymorphisms was significantly related to the risk of diffuse-type gastric cancer. No significant association was found between risk of gastric cancer and the IL1B+3954 polymorphism. Individuals carrying 2 or more of the risk-associated alleles (IL1B-31C, IL1RN *2 and IL10-592C) were at increased risk for intestinal-type gastric cancer, compared to those with 0 or 1 risk-associated allele. The risk from multiple risk-associated alleles was especially high in subjects infected with CagA positive H. pylori. Our results support the identification of the IL1B-31 promoter polymorphism as a useful marker for risk of intestinal type gastric cancer in persons with CagA positive H. pylori infections.     

Seroreactivity to Helicobacter pylori Antigens as a Risk Indicatorof Gastric Cancer

Background: Multiple etiologic factors are suspected to cause gastric cancer, the most important of whichis infection with virulent types of Helicobacter pylori. Materials and Methods: We have compared 102 gastriccancer patients with 122 non-ulcer, non-cancer dyspeptic patients. Gastric specimens were evaluated for H.pylori infection by tissue-based detection methods. Patient sera underwent antigen-specific ELISA and westernblotting using a Helicoblot 2.1 kit and antibody responses to various H. pylori antigens were assessed. Results:The absolute majority (97-100%) of both groups were H. pylori seropositive. Multivariate regression analysisdemonstrated serum antibodies to the low molecular weight 35kDa protein to be protective and reduce the riskof gastric cancer by 60% (OR:0.4; 95%CI:0.1-0.9). Conversely, seroreactivity to the 89kDa (VacA) protein wassignificantly higher in gastric cancer patients (OR:2.7; 95%CI:1.0-7.1). There was a highly significant association(p<0.001) between seroreactivity to the 116kDa (CagA) and 89kDa (VacA) proteins, and double positive subjectswere found at nearly five fold (OR:4.9; 95%CI:1.0-24.4) enhanced risk of gastric cancer as compared to doublenegative subjects. Conclusions: Seroreactivity to H. pylori low (35kDa) and high (116kDa/89kDa) molecularweight antigens were respectively revealed as protective and risk indicators for gastric cancer.     

Chronic Hepatitis B Virus Infection and Risk of Pancreatic Cancer: A Meta-analysis

Objectives: A number of studies have shown that chronic hepatitis B virus infection is implicated insusceptibility to pancreatic cancer. However, the results are still controversial. This meta-analysis aimed toquantitatively assess the relationship between chronic hepatitis B virus infection and incidence of pancreaticcancer of cohort and case-control studies. Methods: A literature search was performed for entries from 1990 to2012 using PUBMED and EMBASE. Studies were included if they reported odds ratios (ORs) and corresponding95% CIs of pancreatic cancer with respect to the infection of hepatitis B virus. Results: Eight studies met theinclusion criteria, which included five case-control studies and three cohort studies. Compared with individualswho have not infection of hepatitis B virus, the pooled OR of pancreatic cancer was 1.403 (95%CI: 1.139-1.729,P=0.001) for patients with hepatitis B virus infection. Sub-group analysis by study design showed that thesummary OR was 1.43 (95%CI: 1.06-1.94, P=0.021) when pooling case-control studies and 1.31 (95%CI: 1.00-1.72, P=0.05) when pooling cohort studies. Conclusion: Findings from this meta-analysis suggest that chronichepatitis B virus infection may increase the risk of pancreatic cancer. This relationship needs to be confirmedby further follow-up studies.     

Peroxisome Proliferator-Activated Receptor-Gamma Pro12Ala Polymorphism Could be a Risk Factor for Gastric Cancer

Background: Due to the strong inhibitory effects of PPARγ gene on the growth of cancer cells, the role ofPro12Ala polymorphism in PPARγ gene has been extensively investigated in cancer recently. However, theresults were inconsistent according to cancer type. The aim of this study was to comprehensively evaluate thePPARγ Pro12Ala polymorphism and gastric cancer susceptibility. Materials and Methods: Search strategieswere conducted in Pubmed, Medline (Ovid), Chinese biomedical database (CBM), China national knowledgeinfrastructure (CNKI), VIP, and Wanfang database, covering all publications, with the last search up to November01, 2014. The strength of association between PPARγ Pro12Ala polymorphism and gastric cancer risk was assessedby OR with 95%CI. Results: A total of 546 cases and 827 controls in 5 case-control studies were included in thismeta-analysis. The results indicated that the variant G allele carriers (CG+GG) had a 2.31 times higher risk forgastric cancer when compared with the homozygote CC (odds ratio (OR)=2.31, 95% confidence interval (CI)=1.67-3.21 for CG+GG vs. CC). In the subgroup analysis by ethnicity, significantly elevated risks were both found inAsians (OR=2.56, 95% CI=1.42-4.64) and Caucasians (OR=2.20, 95% CI=1.48-3.25). Similarly, in the subgroupanalysis by H. pylori status, a significantly increased risk was identified in H. pylori (+) populations (OR=3.68,95%CI=2.07-6.52), but not in H. pylori(-) populations (OR=1.17, 95%CI=0.58-2.39). Conclusions: This pooledanalysis suggested that the PPARγ Pro12Ala polymorphism could be an independent predictive risk factor forgastric cancer especially in H. pylori infected populations in Asians and Caucasians. Nevertheless, prospectivelydesigned cohort studies are needed to further investigate gene-gene and gene-environment interactions to confirmthe combined effects of PPARγ Pro12Ala polymorphisms and H. pylori infection on gastric cancer risk.     

The DNA Repair Gene ERCC6 rs1917799 Polymorphism is Associated with Gastric Cancer Risk in Chinese

Objective: Excision repair cross-complementing group 6 (ERCC6) is a major component of the nucleotideexcision repair pathway that plays an important role in maintaining genomic stability and integrity. Severalrecent studies suggested a link of ERCC6 polymorphisms with susceptibility to various cancers. However, therelation of ERCC6 polymorphism with gastric cancer (GC) risk remains elusive. In this sex- and age- matchedcase-control study including 402 GC cases and 804 cancer-free controls, we aimed to investigate the associationbetween a potentially functional polymorphism (rs1917799 T>G) in the ERCC6 regulatory region and GC risk.Methods: The genotypes of rs1917799 were determined by Sequenom MassARRAY platform and the status ofHelicobacter pylori infection was detected by enzyme-linked immunosorbent assay. Odd ratios (ORs) and 95%confidential interval (CI) were calculated by logistic regression analysis. Results: Compared with the commonTT genotype, the ERCC6 rs1917799 GG genotype was associated with increased GC risk (adjusted OR=1.46,95%CI: 1.03-2.08, P=0.035). When compared with (GT+TT) genotypes, the GG genotype also demonstrateda statistical association with increased GC risk (adjusted OR=1.38, 95%CI: 1.01-1.89, P=0.044). This was alsoobserved for the male subpopulation (GG vs. TT: adjusted OR=1.71, 95%CI: 1.12-2.62, P=0.013; G allele vs.T allele: adjusted OR=1.32, 95%CI: 1.07-1.62, P=0.009). Genetic effects on increased GC risk tended to beenhanced by H. pylori infection, smoking and drinking, but their interaction effects on GC risk did not reachstatistical significance. Conclusions: ERCC6 rs1917799 GG genotype might be associated with increased GCrisk in Chinese, especially in males.     

MTHFR polymorphisms and pancreatic cancer risk: lack of evidence from a meta-analysis

Objective: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported tobe associated with pancreatic cancer, but the published studies had yielded inconsistent results.We thereforeperformed the present meta-analysis. Methods: A search of Google scholar, PubMed, Cochrane Library andCNKI databases before April 2012 was conducted to summarize associations of MTHFR polymorphisms withpancreatic cancer risk. Assessment was with odds ratios (ORs) and 95% confidence intervals (CIs). Publicationbias were also calculated. Results: Four relative studies on MTHFR gene polymorphisms (C667T and A1298C)were involved in this meta-analysis. Overall, C667T(TT vs. CC : OR = 1.61, 95%CI = 0.78 - 3.34; TT vs. CT :OR = 1.41, 95%CI = 0.88-2.25; dominant model: OR = 0.68, 95%CI = 0.40-1.17; recessive model: OR = 0.82,95%CI = 0.52-1.30) and A1298C(CC vs. AA:OR=1.01, 95%CI=0.47-2.17; CC vs. AC: OR=0.99,95%CI=0.46-2.14;dominant model: OR=1.01, 95%CI = 0.47-2.20; recessive model: OR = 1.01, 95%CI = 0.80-1.26) did not increasepancreatic cancer risk. Conclusion: This meta-analysis indicated that MTHFR polymorphisms (C667T andA1298C) were not associated with pancreatic cancer risk.     

The Exonuclease 1 Glu589Lys Gene Polymorphism and Cancer Susceptibility: Evidence Based on a Meta-analysis

Background: Published studies on the association between the exonuclease 1 (EXO1) Glu589Lys polymorphismand cancer susceptibility have yielded conflicting results. Thus, a meta-analysis of published studies was performedto assess the possible association. Materials and Methods: All eligible case-control studies published up to January2013 on the association between the EXO1 Glu589Lys polymorphism and cancer susceptibility were identified bysearching PubMed, Web of Science, Science Direct and hand search. Either fixed-effect or random-effect modelswere used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs) using the ComprehensiveMeta-Analysis software version 2.2. Results: A total of 4,391 cancer cases and 4,339 controls from 10 studieswere included. Overall, no significant association between the EXO1 Glu589Lys polymorphism and cancersusceptibility was observed in either genetic model. However; in subgroup analyses by cancer type, a significantassociation between EXO1 Glu589Lys and lung cancer risk was found (Lys vs Glu: OR=1.23, 95%CI=1.07-1.41, pheterogeneity=0.05). Further, subgroup analysis by ethnicity indicated that there was a statistically increasedcancer risk in Asians (Lys vs Glu: OR=1.42, 95%CI=1.30-1.55, pheterogeneity=0.07; Lys/Lys vs Glu/Glu: OR=1.93,95%CI=1.20-3.12, pheterogeneity=0.01; Lys/Lys+Glu/Lys vs Glu/Glu: OR=1.52, 95%CI=1.37-1.68, pheterogeneity=0.42;Lys/Lys vs Glu/Lys+Glu/Glu: OR=1.68, 95%CI=1.07-2.65, pheterogeneity=0.02). However, significant association wasabsent in Caucasians. Conclusions: This meta-analysis suggests, for the first time, that the EXO1 Glu589Lyspolymorphism is not associated with overall cancer susceptibility, although marginal associations were found forlung cancer and Asian subgroups. Additional well-designed studies with larger sample size focusing on differentethnicities and cancer types are needed to confirm these findings.     

The 765G>C Polymorphism in the Cyclooxygenase-2 Gene and Gastric Cancer Risk: an Update by Meta-analysis

Background: The 765G>C polymorphism in cyclooxygenase-2 (COX-2) gene has been extensively investigatedfor association with gastric cancer (GC). However, the results of different studies have been inconsistent. The aimof this study is to comprehensively evaluate the genetic risk of -765G>C polymorphism in the COX-2 gene forGC. Materials and Methods: We searched Pubmed, Embase, Medline, CNKI database, Wanfang database, Weipudatabase, and Chinese Biomedical database, covering all publications (last search been performed on Jan 10,2014). Statistical analyses were performed using Revman 5.2 and STATA 10.0 software. Results: A total of 1,874cases and 3,005 controls in 10 case-control studies were included in this meta-analysis. The results indicated thatthe variant C allele carriers (GC+CC) had a 69% increased risk of GC when compared with the homozygote GG(odds ratio (OR)=1.69, 95% confidence interval (CI), 1.10-2.61 for GC+CC vs GG). In the subgroup analysis byethnicity, significant elevated risks were associated with C allele carriers in Asians (OR=1.75, 95%CI=1.40-2.18,and p<0.00001) and in Indians (OR=8.38, 95%CI=4.34-16.16, and p<0.00001) but not in Caucasians (OR=1.07,95%CI=0.81-1.42, and p=0.62) or in Dutch (OR=0.53, 95%CI= 0.33-0.87, and p= 0.01).In the subgroup analysisby Helicobacter pylori (H. pylori) status, a significantly increased risk was identified among H. pylori (+) (OR=3.58,95%CI=2.33-3.50, and p<0.00001) and H. pylori (-) (OR=2.32, 95%CI=1.46-3.69, and p=0.0004). Conclusions:This meta-analysis suggested that the -765G>C polymorphism in the COX-2 gene could be a risk factor for GCin Asians and Indians.     

Quantitative assessment of the association between glutathione S-transferase P1 Ile105Val polymorphism and bladder cancer risk

Previous studies investigating the association between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and bladder cancer risk reported controversial results. This study aimed to quantify the strength of the association between GSTP1 Ile105Val polymorphism and bladder cancer risk by performing a meta-analysis. We searched the PubMed, Embase, and Wanfang databases for publications on the association between GSTP1 Ile105Val polymorphism and bladder cancer risk. We estimated the pooled odds ratios (ORs) with their confidence intervals (95 %CIs) to assess the association. Twenty-five individual studies with a total of 12,360 subjects were finally included. Meta-analysis of all 25 studies showed that GSTP1 Ile105Val polymorphism was associated with increased risk of bladder cancer risk under four genetic comparison models (for G versus A, random-effect OR?=?1.19, 95 %CI 1.05–1.35; for GG versus AA, random-effect OR?=?1.49, 95 %CI 1.12–1.97; for GG/GA versus AA, random-effect OR?=?1.20, 95 %CI 1.03–1.39; for GG versus GA/AA, random-effect OR?=?1.41, 95 %CI 1.10–1.80). Sensitivity analysis showed that GSTP1 Ile105Val polymorphism was still associated with bladder cancer risk under three genetic comparison models (for G versus A, random-effects OR?=?1.13, 95 %CI 1.01–1.26; for GG versus AA, random-effects OR?=?1.29, 95 %CI 1.01–1.65; for GG versus GA/AA, random-effects OR?=?1.19, 95 %CI 1.04–1.35). No evidence of publication bias was observed. This meta-analysis shows that there is an obvious association between GSTP1 Ile105ValIle105Val polymorphism and bladder cancer risk, and GSTP1 ILE105VAL polymorphism contributes to bladder cancer risk.     

Fruit and Vegetable Intake and Stomach Cancer among Male Adults: A Case-Control Study in Northern Viet Nam

Objective: This study investigated the association between fruit and vegetable intake and stomach cancer, with considering the impacts of Helicobacter pylori (H. pylori) infection and tobacco smoking. Methods: A case-control study featuring 80 male incident stomach-cancer cases and 126 male controls was conducted in a general hospital in Viet Nam. A semi-quantitative food frequency and demographic lifestyle questionnaire were used; and venous blood samples were collected to determine H. pylori status by IgG ELISA. The respective associations between fruit and vegetable intake and stomach cancer were examined using unconditional logistic regression analysis with adjustments for possible cofactors. Results: Fruit intake and stomach cancer showed a weak inverse association when this became non-significant after adjusting for H. pylori infection (OR = 0.50, 95%CI: 0.22–1.12, p trend = 0.094). Stratifying by H. pylori status returned a negative trend for fruit intake and stomach cancer among H. pylori-negative participants (OR = 0.21, 95%CI: 0.06–0.69, p trend = 0.010), but no significant interaction for H. pylori-positive participants (OR = 0.76, 95%CI: 0.21–2.68, p trend = 0.670). Vegetable intake and stomach cancer showed no association, regardless of H. pylori status. Compared to ever-smokers with low intake, never-smokers with high vegetable (OR = 0.25, 95% CI: 0.06–0.95) and fruit intake (OR = 0.20, 95%CI: 0.06–0.65) showed the lowest odds of stomach cancer. Conclusions: Fruit, but not vegetable, intake showed a weak inverse association with stomach cancer. H. pylori infection and tobacco-smoking status may influence the protective effects of fruit and vegetable intake on stomach cancer.     

Promoter methylation of p16 associated with Helicobacter pylori infection in precancerous gastric lesions: a population-based study

To investigate the relationship between p16 methylation and Helicobacter pylori infection in precancerous gastric lesions, a population-based study was conducted in Linqu County, a high-risk area of gastric cancer in China. Methylation status of p16 was evaluated by methylation-specific polymerase chain reaction in 920 subjects with precancerous gastric lesions. H. pylori status was determined by 13C-urea breath test and the density of H. pylori in biopsy specimens used for detecting methylation status was assessed by the modified Giemsa stain. The frequency of p16 methylation was significantly higher in subjects with H. pylori positive than those with H. pylori negative in each category of gastric lesion (p<0.001, respectively). Compared with H. pylori negative, the odds ratios (ORs) of p16 methylation were markedly elevated in subjects with H. pylori positive for superficial gastritis (OR, 9.45; 95% confidence interval [CI]: 2.94-30.41), chronic atrophic gastritis (OR, 15.92; 95%CI: 7.60-33.36), intestinal metaplasia (OR, 4.46; 95%CI: 2.44-8.13), indefinite dysplasia (OR, 3.67; 95%CI: 1.90-7.10), and dysplasia (OR, 2.48; 95%CI: 1.02-5.99). Moreover, the frequencies of p16 methylation increased steadily with the severity of H. pylori density in gastric mucosa. Compared with H. pylori negative, the OR of p16 methylation was 1.02-16.13 times higher in subjects with mild H. pylori infection, and 2.69-38.73 times higher in those with moderate/severe infection, respectively. Our findings indicate that p16 methylation was significantly associated with H. pylori infection in precancerous gastric lesions, suggesting that H. pylori infection could potently induce methylation of p16 CpG island.     

MTHFR Gene Polymorphisms are Not Involved in Pancreatic Cancer Risk: A Meta-analysis

Purpose: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to beassociated with pancreatic cancer, but the published studies have yielded inconsistent results. This study assessedthe relationship between MTHFR gene polymorphisms and the risk for pancreatic cancer using a meta-analysisapproach. Methods:A search of Google scholar, PubMed, Cochrane Library and CNKI databases before April 2012was performed, and then associations of the MTHFR polymorphisms with pancreatic cancer risk were summarized.The association was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was alsocalculated. Results: Four relative studies on MTHFR gene polymorphisms (C667T and A1298C) were included inthis meta-analysis. Overall, C667T (TT vs. CC:OR=1.61,95%CI=0.78-3.34; TT vs. CT: OR=1.41,95%CI=0.88-2.25;Dominant model:OR=0.68,95%CI=0.40-1.17; Recessive model: OR=0.82,95%CI=0.52-1.30) and A1298C (CCvs. AA:OR=1.01,95%CI=0.47-2.17; CC vs. AC: OR=0.99,95%CI=0.46-2.14; Dominant model:OR=1.01,95%CI=0.47-2.20; Recessive model: OR=1.01,95%CI=0.80-1.26) did not increase pancreatic cancer risk.Conclusions: This meta-analysis indicated that MTHFR polymorphisms (C667T and A1298C) are not associatedwith pancreatic cancer risk.     

Clinical Characteristics and Helicobacter pylori Status of Gastric Cancer in Thailand

Background: Gastric cancer is the second leading course of cancer death worldwide and H. pylori infectionis an important risk factor for gastric cancer development. This study was design to evaluate the clinical,pathological features, survival rate and prevalence of H. pylori infection in gastric cancer in Thailand. Materialsand Methods: Clinical information, histological features, endoscopic findings and H. pylori status were collectedfrom gastric cancer patients from Thammasat university hospital during June 1996-December 2011. H. pyloriinfection was assessed by histological evaluation, rapid urease test and serological test. Clinical information,endoscopic findings and histopathology of all patients were recorded and compared between patients with activeor non-active H. pylori infection. Results: A total of 100 gastric cancer patients (55 men and 45 women withmean age of 55±16.8 years) were enrolled in this study. Common presenting symptoms were dyspepsia (74%),weight loss (66%), anemia (63%) and anorexia (38%). Mean duration of symptoms prior to diagnosis was 98days. Overall prevalence of H. pylori infection was 83% and active H. pylori infection was 40%. 1-year and5-year survival rates were 43% and 0%. There was no significant difference between active H. pylori infectionin different locations (proximal vs non-proximal: 47.1% vs 48.5%; P-value = 0.9, OR=0.9; 95%CI =0.3-3.1) andhistology of gastric cancer (diffuse type vs intestinal type: 47.4% vs 50%; P-value= 0.8, OR=0.9, 95%CI=0.3-2.7).However, linitis plastica was significantly more common in non-active than active H. pylori infection (27.9% vs0%; P-value <0.0001, OR =13.3, 95%CI=3.2-64.5). Moreover, gastric cancer stage 4 was higher in non-active thanactive H. pylori infection (93% vs 50%, P-value<0.001). Conclusions: Prevalence of H. pylori infection in Thaigastric cancer patients was high but active infection was low. Most gastric cancer patients presented in advancestage and had a grave prognosis. Screening for gastric cancer in high risk individuals might be an appropriatetool for early detection and improve the treatment outcome for this particular disease in Thailand.     

Prevalence and Risk Factors for Helicobacter Pylori Infection among Healthy Inhabitants in Northern Jakarta,Indonesia

Background: The prevalence of Helicobacter pylori (H. pylori) infection in Indonesia has been reported to be exceedingly low. The purpose of our study was to confirm whether this is the case in Northern Jakarta using a sensitive 13C-urea breath test (UBT), and to examine any associations with lifestyle/environment factors and potential routes of transmission. Methods: We recruited a total of 196 subjects from a low-income community in Northern Jakarta, Indonesia, data from 193 who completed a questionnaire about their lifestyle/environment and had UBT being included as the final. Odds ratios (ORs) adjusted for sex and age with 95% confidence intervals (CIs) were calculated using a logistic regression model. Results: The overall H. pylori infection rate was 15.0% (95%CI, 10.3-20.9), with variation among Javanese (9.1%, total=77), Buginese (40.0%, 35), Betawi (9.1%, 33), Sundanese (3.7%, 27), and Batak (40.0%, 5). On multivariate analysis, the ORs for intake of soybean milk, cucumber more than once a week, infrequent hand washing practice before meals, and alcohol consumption were 0.10 (95%CI: 0.01-0.97), 6.61 (95%CI: 1.87-23.3), 4.10 (95%CI: 1.15-14.6), and 61.9 (95%CI: 1.67-2300.8), respectively. Rates for Buginese (OR=7.84; 95%CI: 1.82-33.8) and Batak (OR=20.1; 95%CI: 1.90-213.2) were significantly higher than for Javanese. Conclusions: The H. pylori infection rate in this study was relatively low, in line with previous studies. Regarding ethnicity factors, Buginese and Batak reported eating food using fingers more frequently than Javanese, Betawi, and Sundanese. Our study indicated that person-person transmission is possible in this low prevalence area. The low infection rates for H. pylori among Javanese, Betawi, and Sundanese ethnics could be partly due to their sanitary practices.     

Helicobacter pylori Infection Impacts on Functional Dyspepsia in Thailand

Background: Helicobacter pylori (H. pylori) is a well known major cause of gastric cancer and even whenasymptomatic infected patients are at elevated risk. Functional dyspepsia (FD) is also one of the most commongastrointestinal diseases, which greatly impacts the quality of life. H. pylori infection and psychosocial stress arefrequently associated with FD but limited studies have confirmed the relationships, especially in Southeast Asiancountries. Here we aimed to investigate the prevalence and impact of H. pylori infection, anxiety and depressionon Thai FD patients. Materials and Methods: This cross-sectional study was conducted in a tertiary care centerin Thailand, during February 2013-January 2014. All FD patients were diagnosed and categorized by Rome IIIcriteria into epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) groups. The HospitalAnxiety and Depression Scale was used to evaluate psychological status. The presence of H. pylori was definedas positive with H. pylori culture, positive rapid urease test or positive histology. Results: Three hundred FDpatients were included, 174 (58%) female. Overall mean age was 54.8+15.1 years. There were 192 (64%) patientswith PDS and 108 (36%) with EPS. H. pylori infection was demonstrated in 70 (23.3%) patients. Anxiety anddepression were documented in 69 (23%) and 22 (7.3%), respectively. H. pylori infection, anxiety and depressionwere significantly higher in PDS than EPS patients (27.1% vs 16.7%; p=0.04; OR=1.86; 95%CI=1.01-3.53 and29.7% vs 11.1%; p=0.0002; OR=3.4; 95%CI=1.7-7.1 and 10.4% vs 1.9%; p=0.006; OR=6.2; 95%CI=1.4-38.9,respectively). Conclusions: H. pylori infection, anxiety and depression were commonly found in Thai FD patientsand more prevalent in PDS than EPS. H. pylori eradication might be the key to success for the treatment of ThaiFD patients and prevent the development of gastric cancer.