Determinants of gastric CDX2 expression: a study in Mozambique

As CDX2 expression precedes the occurrence of gastric preneoplastic lesions in the intestinal differentiation pathway, study of these steps of gastric carcinogenesis may contribute toward understanding the early effects of gastric cancer determinants. Our aim was to quantify the association between Helicobacter pylori infection and other environmental factors and the gastric expression of CDX2. Dyspeptic patients undergoing an upper digestive endoscopy (Gastroenterology Department, Maputo Central Hospital) were consecutively invited to participate in this study and classified as having normal stomach/chronic nonatrophic gastritis (NS/CNAG), chronic atrophic gastritis (CAG), or intestinal metaplasia (IM). For all patients with CAG or IM and a subsample of NS/CNAG patients (sex-matched and age-matched, 1?:?2), H. pylori infection and CDX2 gene expression were assessed by histology and PCR and by immunohistochemistry, respectively. Age-adjusted, sex-adjusted, education-adjusted, and H. pylori infection-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were computed. CDX2 expression was observed in 56 NS/CNAG (49.1%), 39 CAG (86.7%), and all IM patients (n=12). It was more frequent among the H. pylori-infected patients (OR=2.26, 95% CI: 1.00-5.15). Infection with high-virulence strains was associated with CDX2 expression in patients with CAG (cagA, OR=3.20, 95% CI: 1.35-7.52) and IM (vacA m1, OR=5.86, 95% CI: 1.08-31.62). Patients with a lower frequency of vegetable consumption had a higher risk of marked CDX2 expression (OR=3.64, 95% CI: 1.02-12.95). The virulence of the infecting strains and vegetable consumption were associated with CDX2 expression and may play a role in the progression to more advanced lesions.     

Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer

We conducted a longitudinal cohort study to determine the association of Helicobacter pylori infection and the progression of chronic atrophic gastritis (CAG) with gastric cancer. A cohort of 4655 healthy asymptomatic subjects was followed for a mean period of 7.7 years. H. pylori infection was established by serum specific antibodies and the presence of CAG was confirmed by serum pepsinogen. During the follow-up period, 45 gastric cancer cases were detected (incidence rate, 126/100000 person-years). A univariate analysis after adjustment for age showed that both H. pylori and CAG were significantly associated with gastric cancer. To clarify the interaction between H. pylori and CAG, an analysis stratified by H. pylori- and CAG-status was performed. No cancer developed in the H. pylori(-)/CAG(-) group during the study period. This supports the theory that it is quite rare for any type of gastric cancer to develop in an H. pylori-free healthy stomach. With the progression of H. pylori-induced gastritis, the risk of gastric cancer increased in a stepwise fashion from CAG-free gastritis [H. pylori(+)/CAG(-) group] (HR=7.13, 95%CI=0.95-53.33) to CAG [H. pylori(+)/CAG(+) group] (HR=14.85, 95%CI=1.96-107.7) and finally to severe CAG with extensive intestinal metaplasia [H. pylori(-)/CAG(+) group] (HR=61.85, 95%CI=5.6-682.64) in which loss of H. pylori from the stomach is observed. Therefore, it is probable that H. pylori alone is not directly associated with stomach carcinogenesis. Instead, H. pylori appears to influence stomach carcinogenesis through the development of CAG. The observed positive correlation between the extent of H. pylori-induced gastritis and the development of cancer was strong, especially for the intestinal type. These results are compelling evidence that severe gastritis with extensive intestinal metaplasia is a major risk factor for gastric cancer, and they confirm the previously described model of stomach carcinogenesis: the gastritis-metaplasia-carcinoma sequence.     

Helicobacter pylori, atrophic fundal gastritis and risk for gastric adenocarcinoma

Fundal atrophic gastritis and Helicobacter pylori have been implicated as possible etiologic factors in gastric cancer. This case-control study was performed to determine which risk factor is more closely related to gastric cancer. The endoscopic Congo red test was performed to evaluate the extent of fundal atrophic gastritis in 43 patients with gastric cancer and 86 cancer-free control subjects, who were individually matched by age, sex, and date of endoscopy (within 3 months). The prevalance of H. pylori infection and severe fundal gastritis were significantly higher in patients with differentiated adenocarcinoma, but not with undifferentiated adenocarcinoma, than in control subjects. The odds ratios for differentiated and undifferentiated adenocarcinomas were 6.85 (95% confidence interval, 1.94-11.82) and 1.50 (95% CI, 0.84-3.11), respectively. However, the odds ratio of H. pylori infection was greater than that of severe fundal gastritis. Moreover, multivariate analysis provided similar results. H. pylori infection is an independent indicator of a higher risk of the differentiated adenocarcinomas of the stomach than is severe fundal gastritis.     

Elevated risk of colorectal adenoma with Helicobacter pylori-related chronic gastritis: a population-based case-control study

This study investigated correlations between Helicobacter pylori infection or chronic atrophic gastritis (CAG) and risk of colorectal adenoma in a population-based case-control study. Subjects comprised asymptomatic, middle-aged, male Japanese factory workers who participated in an annual health check-up program, including cancer screening with colonoscopy. We selected 239 colorectal adenoma cases based on histological evaluation and 239 age-matched adenoma-free controls, and evaluated colorectal adenoma risk according to stage of H. pylori-related chronic gastritis as determined by serum tests for H. pylori antibody titer and pepsinogen. Subjects with colorectal adenoma were more likely to be smokers and have hypercholesterolemia. H. pylori infection was a risk factor for adenoma as a whole (crude odds ratio [OR]: 2.26, 95% confidence interval [CI]: 1.44-3.55). Analysis of distal adenoma cases showed that adenoma risk was significantly increased in the presence of H. pylori infection, but there was no further increase in risk with CAG. In contrast, proximal adenoma risk increased stepwise with the presence and progression of H. pylori-related chronic gastritis and showed a maximal and significant increase with CAG (crude OR: 4.51, 95% CI: 1.43-14.2). Subjects with more extensive and severe gastritis showed still higher risk not only for proximal but also for distal adenoma. H. pylori-related chronic gastritis is likely to be involved in the development of colorectal neoplasms, and its progression appears to increase the risk, particularly for proximal adenomas. Knowing the H. pylori-related chronic gastritis stage will probably be useful for evaluation of risk for colorectal neoplasia.     

Patients younger than 40 years with gastric carcinoma: Helicobacter pylori genotype and associated gastritis phenotype.

BACKGROUND: In the general population, Helicobacter pylori (H. pylori), particularly the cagA positive strain, has been associated with intestinal-type gastric carcinoma. Gastric carcinomas are rarely observed in patients age < or = 40 years. Host-related factors have been thought to be more important than environmental agents in these early-onset cancers. The aim of this study was to ascertain the possible role of H. pylori infection and that of cagA positive strains in the development of gastric carcinoma in these young patients. METHODS: In this case-control study, 105 gastric carcinoma patients (male-to-female ratio = 1.1; mean age, 34.4 years; range, 16-40 years) and an equal number of controls (matched for gender and age) were retrospectively selected from the same geographic area. The phenotypes of gastritis and H. pylori were histologically assessed, and the presence of the ureC gene, which is indicative of H. pylori infection, and the cagA genotype were determined by polymerase chain reaction. Gastric carcinoma risk was calculated by both univariate and multivariate statistical methods, taking into account the cancer phenotype, the gastritis phenotype detected in both patients and controls, and the H. pylori genotype. RESULTS: For 74 diffuse and 31 intestinal gastric carcinomas, multivariate logistic regression analysis produced results consistent with those of univariate statistical tests, showing a significant association between gastric carcinoma and both H. pylori infection (odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.52-5.11) and cagA positive status (OR = 2.94; 95% CI = 1.56-5.52). CONCLUSIONS: In young Italian patients with gastric carcinoma, the significant association with cagA positive H. pylori infection suggests that the bacterium has an etiologic role in both diffuse-type and intestinal-type gastric carcinoma.     

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.     

Genetic polymorphism of PSCA and risk of advanced precancerous gastric lesions in a Chinese population

Objective: To evaluate the relationship between the genetic polymorphism of prostate stem cell antigen (PSCA) and the risk of advanced precancerous gastric lesions including intestinal metaplasia(IM) and dysplasia(Dys), a population-based study was conducted in Linqu County, a high-risk area of gastric cancer (GC) in China.Methods: The prevalence of gastric lesions including superficial gastritis(SG), chronic atrophic gastritis(CAG), IM and Dys was determined by histopathologic examination. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The effects of PSCA genetic variant on the risks of IM and Dys were calculated by unconditional logistic regression.Results: Multivariate analysis revealed subjects carrying PSCA rs2294008 CT/TT genotype were associated with an increased risk of IM (OR=1.38, 95% CI=1.11-1.71) and Dys (OR=1.75, 95% CI=1.36-2.26), especially for subjects with H.pylori infection (IM: OR=1.34, 95% CI=1.05-1.71; Dys: OR=1.82, 95% CI=1.37-2.42). Furthermore, H. pylori infection and PSCA rs2294008 CT/TT genotype were observed to jointly elevate the risk of 1M (OR=3.32, 95% CI=2.33-4.71) and Dys (OR=4.58, 95% CI=2.99-7.04).Conclusion: This study suggested that PSCA rs2294008 might have an impact on the risk of IM or Dys among the high risk population of GC.     

Smoking Behavior and Risk of Helicobacter Pylori Infection,Gastric Atrophy and Gastric Cancer in Japanese

Although many studies have shown that smoking is an established risk factor for gastric cancer, relatively few studies have investigated on which step smoking has effects in Helicobacter pylori (H. pylori) related gastric carcinogenesis. In this study we investigated the association of smoking with risk of three steps leading to gastric cancer: H. pylori infection, gastric atrophy, and gastric cancer. Among the participants who visited Aichi Cancer Center Hospital from year 2001 to 2005, 583 cases diagnosed as gastric cancer and age-and sex-frequency-matched 1,742 cancer free controls were sampled, from whom those without serum samples or without information about smoking habit were excluded, leaving 576 cases and 1,599 controls eligible for the analyses. Anti- H. pylori IgG antibody and serum pepsinogens (PG) were measured to detect H. pylori infection and gastric atrophy. Smoking status was asked by a self-administered questionnaire. The odds ratio (OR) of H. pylori infection, as well as the OR of gastric atrophy among the H. pylori seropositive controls was not significant for smokers. The age- and sex-adjusted OR of gastric cancer was significantly elevated relative to the subjects with gastric atrophy: OR=1.62 (95% confidence interval (CI), 1.19-2.22; P=0.002) for ever smokers and 2.52 (1.75-3.64; P<0.001) for current smokers, relative to never smokers. This study revealed that smoking behavior contributed to the increased risk of gastric carcinogenesis from gastric atrophy, but had little influence on H. pylori infection or gastric atrophy development.     

Helicobacter pylori and malignant lymphoma in Spain.

Helicobacter pylori has been associated with gastric adenocarcinoma and gastric lymphoma. We report on the systematic evaluation of serologic detection of H. pylori in a lymphoma case-control study. METHODS: Cases (N = 536) were consecutive patients newly diagnosed with a lymphoid malignancy between 1998 and 2002 in four centers in Spain. Lymphomas were diagnosed and classified using the WHO Classification. Controls (N = 603) were hospitalized patients frequency-matched to the cases by 5-year age group, sex, and study center. Severe immunocompromised patients were excluded as controls. Patients underwent a personal interview and blood sampling. H. pylori infection was evaluated by the presence of IgG antibodies using the Premier enzyme immunoassay kit (Meridian Diagnostics Inc., Cincinnati, OH). Logistic regression analysis was used to estimate the odds ratios and 95% confidence intervals (OR, 95% CI) for lymphoma categories. RESULTS: Anti-H. pylori antibodies were detected in 68.5% of the cases and 71.3% of the controls (P = 0.29) H. pylori was associated with a 3-fold excess risk of splenic marginal B-cell lymphoma (OR = 3.97, 95% CI = 0.92-17.16). H. pylori was not associated with an overall increased risk of extranodal lymphomas (OR = 0.73, 95% CI = 0.44-1.22) but when specific sites were explored, the four mucosa-associated lymphoid tissue and the six diffuse large B-cell lymphomas primary localized in the stomach were all H. pylori seropositive. CONCLUSION: Persistent infection with H. pylori may be implicated in the development of lymphomas of the gastric mucosa and of the spleen. These results could have clinical implications in the management of splenic marginal zone lymphomas.     

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.     

Role of Helicobacter pylori infection among offspring or siblings of gastric cancer patients

A positive family history is an increased risk factor for gastric cancer within family members, and one of the possible causes of this is the intrafamilial clustering of Helicobacter pylori infection. Our study examined the prevalence of H. pylori infection, serum antibodies to CagA and VacA and atrophic gastritis and/or intestinal metaplasia in the offspring or siblings of gastric cancer patients. A total of 726 subjects included 300 relatives of 300 separate gastric cancer patients and 426 controls. All subjects underwent upper gastrointestinal endoscopic examination with a rapid urease test. Blood samples were obtained to test for the presence of serum antibodies to the CagA and VacA proteins of H. pylori. The prevalence of H. pylori infection was higher in relatives of cancer patients (75.3%) than in controls (60.1%), and the adjusted odds ratio was 2.1 (95% CI 1.5-2.9). When either siblings or 2 or more family members were gastric cancer patients, the prevalence of H. pylori infection was much higher compared to the prevalence in controls. There was no specific relationship between CagA and VacA, and H. pylori infection. Atrophic gastritis and/or intestinal metaplasia were more frequently found in H. pylori-infected relatives of cancer patients (26.1%) than in H. pylori-infected controls (12.9%). These results strongly support a role for H. pylori infection in familial aggregation of gastric cancer. The prophylactic eradication of H. pylori infection in the offspring or siblings of gastric cancer patients may be clinically beneficial.     

SNPs of Excision Repair Cross Complementing Group 5 and Gastric Cancer Risk in Chinese Populations

We conducted a case-control study to determine the association between several potential SNPs of excisionrepair cross complementing group 5 (XPG) and gastric cancer susceptibility, and roles of XPG polymorphismsin combination with H.pylori infection in determining risk of gastric cancer. In our study, we collected 337 newlydiagnosed gastric cancer cases and 347 health controls. Three SNPs of XPG, rs2296147T>C, rs2094258C>Tand rs873601G>A, were genotyped using the Taqman real-time PCR method with a 7900 HT sequence detectorsystem. H. pylori infection was diagnosed by ELISA. By multivariate logistic regression analysis, the rs2296147CC genotype was associated with a decreased risk of gastric cancer (OR=0.52, 95% CI=0.27-0.97), and rs2094258TT was associated with elevated risk (OR=2.13, 95% CI=1.22-3.35). Positive H.pylori individuals with rs2094258TT genotypes demonstrated increased risk of gastric cancer (OR=2.13, 95% CI=1.22-3.35), while rs2296147 CCwas associated with lower risk among patients with negative H.pylori (OR=0.45, 95%CI=0.22-0.89). Our findingssuggested that XPG polymorphisms might contribute to risk of gastric cancer among Chinese populations, butthe effect needs to be further validated by larger sample size studies.     

Association between Gastric Pathology and Hepatitis B Virus Infection in Patients with or without Helicobacter Pylori

Background: In the recent years, hepatitis B virus (HBV) infection has been considered as a risk factor for gastriccancer, but further studies are required to confirm these claim. The present study was aimed to evaluate the correlationbetween gastric pathology (precancerous and cancerous conditions) with HBV infection in Helicobacter pylori (H. pylori)positive or negative patients. Methods: In this cross-sectional study, 728 patients under endoscopy examination in YazdShaheed Sadoughi Hospital between 2017 and 2018 were participated. Histopathological analysis was performed ongastric specimens. Hepatitis B surface antigen (HBsAg) in sera was detected by the enzyme-linked immunosorbent assay(ELISA). The relationship between gastric pathology and HBV infection were explored by logistic regression analysis.Results: Of 728 patients, HBsAg and H. pylori infection were detected in 83 and 408 patients, respectively. Sixty ninepatients were co-infected with H. pylori/HBV. H. pylori infection detected in patients with HbsAg positive significantlymore than those were negative for HbsAg (p=0.029). None of HBV/H. pylori co-infected patients did not have normalgastric tissue. A significant difference was seen in histopathology of gastric tissue between HBsAg positive patientswith and without H. pylori infection (p<0.0001). The HBsAg was associated with histopathology of gastric (OR=21.56,95℅CI=7.070-65.741, p<0.001) and as a risk factor for gastritis (OR=12.457, 95℅CI= 3.007-51.614, P=0.001) but nocancer (OR=2.127, 95℅CI=0.242-18.704, P=0.496). Conclusion: The HBV infection alone is associated with someprecancerous lesions but is not correlated with gastric cancer. It can increase development of premalignant conditionsand carcinoma significantly in H. pylori positive patients.     

A past history of gastric ulcers and Helicobacter pylori infection increase the risk of gastric malignant lymphoma

Helicobacter pylori (H. pylori) is a causative agent for peptic ulcers as well as some types of gastric lymphoma; however, the relationship between a peptic ulcer history in combination with H. pylori infection and the risk of gastric lymphoma has not been fully evaluated. To examine this point, we conducted a case-control study with 645 patients histologically diagnosed as having malignant lymphomas and 3225 non-cancer controls. Plasma H. pylori IgG status was assessed for subgroups for which blood samples were available (116 cases and 114 controls). An association with a history of gastric, but not duodenal ulcers was found for gastric lymphoma [odds ratio (OR) = 5.41, 95% confidence interval (CI): 3.12-9.39]. In the examination according to histological subtype, the OR was high for both gastric mucous-associated lymphoid tissue (MALT) lymphoma (OR = 5.54, 95% CI: 2.56-12.01) and diffuse large B-cell lymphoma (DLBCL) (OR = 7.23, 95% CI: 2.62-19.90). In the analysis of H. pylori antibody, the risk of total gastric lymphoma was associated with H. pylori infection (OR = 5.34, 95% CI: 1.42-20.05). A high prevalence of H. pylori infection was also found for both gastric MALT lymphoma (8 out of 10: 80.0%) and DLBCL (8 out of 9: 88.9%). Further, in subgroup analysis of subjects with H. pylori infection, gastric ulcer history, but not duodenal ulcer history was associated with the risk of gastric lymphoma (OR = 4.15, 95% CI: 1.02-16.89). In conclusion, we found a positive association with a past history of gastric ulcer and H. pylori infection for gastric lymphoma, while duodenal ulcer history was no association. These results suggested the risk of gastric lymphoma increased by interaction between H. pylori infection and gastric ulcer history. Further studies are warranted.     

Serological Immunoglobulin G antibody titers to Helicobacter pylori in Japanese Brazilian and Non-Japanese Brazilian gastric cancer patients and controls in S?o Paulo.

Helicobacter pylori (H. pylori) infection is considered a cause of gastric cancer (GC), though evidence for this association is scarce in high-risk areas. Possible case control and/or ethnic differences were investigated as to the presence of H. pylori and its immunogloblin G antibody titer in the multi-ethnic city of S?o Paulo, where the incidence of GC is relatively high. We performed a cross-sectional comparison of antibody titers to H. pylori in Japanese Brazilian, and non-Japanese Brazilian GC patients and their controls. Japanese Brazilian patients were matched by age, sex and ethnicity with two controls, while non-Japanese Brazilian patients were matched as above with one control. Among Japanese Brazilians, 59 of 93 (63.4%) patients with GC and 127 of 186 (68.3%) controls were positive for H. pylori-specific antibody (odds ratio (OR) = 0.80, 95% confidence interval (CI) = 0.47 - 1.36), while among non-Japanese Brazilians, 171 of 228 patients with GC (75.7%) and 178 of 226 controls (78.8%) were positive (OR = 0.84, 95% CI = 0.54 - 1.30). The median serum antibody titer was lower in cases than in controls in both ethnic groups. A high titer (H. pylori titer > or = 50) was associated with less likelihood of GC for both ethnic groups (for Japanese Brazilians, OR = 0.39, 95% CI = 0.16 - 0.92; for non-Japanese Brazilians, OR = 0.56, 95% CI = 0.31 - 1.02). The high titer can be regarded as a sign of the necessity of eradication, and low titer is regarded as a sign of the necessity of close screening for GC in both ethnic groups, because extended atrophy may cause spontaneous disappearance of H. pylori from the stomach.     

A nested case-control study of the association of Helicobacter pylori infection with gastric adenocarcinoma in Korea

In a nested case-control study of 86 cases of gastric adenocarcinoma in relation to Helicobacter pylori infection in the Korean Multi-center Cancer Cohort, the H. pylori IgG seropositivity was 83.7% and that of the 344 matched controls was 80.8%, with a matched odds ratio for H. pylori infection of 1.06 (95% CI, 0.80-1.40).     

Genetic polymorphisms of interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor {alpha} and risk of gastric cancer in a Chinese population

Helicobacter pylori infection and the cytokine-mediated inflammatory responses play important roles in gastric cancer pathogenesis. This case control study was conducted to assess the association between genetic polymorphisms in interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor alpha (TNFalpha), which are involved in H.pylori infection, and risk of gastric cancer. Genotypes were determined by PCR-based denaturing high-performance liquid chromatography analysis and direct DNA sequencing in 250 incident cases with gastric cancer and 300 controls recruited in Northern China. Serum levels of anti-H.pylori IgG and IgA were measured by enzyme-linked immunosorbent assay to indicate H.pylori infection. We found that the risk of gastric cancer was significantly elevated in subjects with the IL-8-251 AA [adjusted odds ratio (OR) 2.02; 95% confidence interval (CI) 1.27-3.21] or IL-10-1082 G (OR 2.02; 95% CI 1.24-3.29) or TNFalpha-308 AG (OR 1.81; 95% CI 1.04-3.14) genotype. An elevated risk of gastric cancer was observed in subjects with H.pylori infection and the IL-8-251 AA genotype (OR 2.54; 95% CI 1.38-4.72) or IL-10-1082 G carriers (OR 2.62; 95% CI 1.42-4.93). An increased OR was also suggested for IL-1B-31 and TNFalpha-238, but confidence intervals included the null value. There was no evidence of increased risk for any of the other polymorphisms evaluated. These findings suggest that genetic polymorphisms in IL-8, IL-10 and TNFalpha may play important roles in developing gastric cancer in the Chinese population.     

Risk of gastric cancer among smokers infected with Helicobacter pylori

Infection with the gastric bacterium Helicobacter pylori (in particular infection with CagA-positive strains) and smoking have been identified as risk factors for the development of gastric cancer. Both risk factors are typically acquired early in life and prevail over decades if not for life. We assessed the individual and joint impact of both risk factors on gastric cancer risk in a population-based case-control study from Germany including 71 patients with histologically verified gastric cancer and 363 patients with colorectal cancer who served as controls. Information on smoking and potential confounding factors was collected by standardized interviews. H. pylori infection was measured serologically by immunoglobulin G antibody titers against H. pylori. In addition, antibodies against the CagA antigen were determined by Western blot. Twenty-seven percent of cases compared with 15% of controls were smokers, and 43% of cases compared with 23% of controls were infected with CagA-positive H. pylori strains. After control for potential confounders, the relative risk of gastric cancer was 2.6 (95% CI 1.2-5.7) for nonsmoking subjects with CagA-positive H. pylori infections and 7.2 (95% CI 2.2-23.6) for smoking subjects with CagA-positive H. pylori infections compared with subjects without these risk factors. The corresponding relative risks for noncardia gastric cancer were 6.1 ( 95% CI 2.3-16.5) and 16.6 (95% CI 4.3-64.2). We conclude that smoking subjects with CagA-positive H. pylori infections have a strongly increased risk of gastric cancer and may be an important group for targeting efforts of prevention and early detection.     

Helicobacter pylori infection, interleukin-1 gene polymorphisms and the risk of colorectal cancer: evidence from a case-control study in Germany

Helicobacter pylori infection is a strong risk factor for gastric cancer. A positive association with colorectal cancer has also been suggested, but available evidence remains inconclusive. In this population-based case-control study we investigated the association between H. pylori seroprevalence and colorectal adenocarcinoma under consideration of pro-inflammatory gene polymorphisms (384 incident cancer patients, 467 matched control subjects). Overall, the H. pylori seroprevalence was higher among cases (51%) than among controls (44%), and a positive association between H. pylori seroprevalence and colorectal adenocarcinoma risk was found, that persisted after adjustment for known potential confounders, including measures of socioeconomic status (odds ratio (OR)=1.41; 95% confidence intervals (CI), 1.06-1.87). Presence of specific H. pylori cytotoxin-associated gene A (CagA) antibodies did not significantly affect the observed risk. Additionally, a pro-inflammatory genotype did not increase the colorectal cancer risk associated with H. pylori infection. H. pylori positive subjects carrying the pro-inflammatory genotypes even had a lower risk.     

Individual and joint impact of family history and Helicobacter pylori infection on the risk of stomach cancer: a nested case-control study

We used 202 cases of stomach cancer and 394 controls nested within the Japan Collaborative Cohort Study For Evaluation of Cancer Risk (JACC study) to investigate whether family history has an independent effect on the risk of stomach cancer after controlling for the Helicobacter pylori infection. A positive history of stomach cancer in one or more first-degree relatives was associated with an increased risk of the disease in women, but not in men after controlling for H. pylori infection and other confounding variables. Women with both a family history and H. pylori infection were associated with more than five-fold increased risk of the disease (OR 5.10, 95% CI 1.58-16.5) compared to those without these factors. These results suggest the existence of inherited susceptibility to the disease in women, and that measurements of H. pylori infection together with the family history allow meaningful evaluation of risk beyond that provided by either factor alone.