Gastric Cancer: the Roles of Diet,Alcohol Drinking,Smoking and Helicobacter pylori in Northeastern Thailand

The incidence of gastric cancer in the countries of South East Asia is variable, ranging from age-standardized ‍rates of 20.9/105 (men) and 10.4/105 (women) in Hanoi, Vietnam to 4.1/105 (men) and 2.1/105 (women) in Khon Kaen, ‍Thailand. The reasons for these differences are unknown. Possible explanations are differences in dietary habits, ‍alcohol drinking, smoking and/or the prevalence of infection with Helicobacter pylori (H. pylori). A case-control ‍study was conducted in Khon Kaen, Thailand, to study the role of these factors in gastric cancer carcinogenesis. 131 ‍gastric cancer cases and 262 matched controls were recruited for the study. Information on dietary habits, alcohol ‍drinking and smoking were collected by a structured questionnaire. Blood samples were available from 111 cases ‍and 232 controls for H. pylori assay. Using an unconditional logistic regression model controlling for age and sex, we ‍assessed the effects of dietary habits, alcohol drinking, smoking and H. pylori infection on the risk of gastric cancer. ‍A high intake of salt (OR=1.8; 95%CI 1.1-3.0) and fermented foods (OR=1.9; 95%CI 1.1-3.3) was found to be ‍associated with an increased risk. Preference for spicy food was not associated with gastric cancer risk in this ‍population. Although there were negative associations between gastric cancer and vegetable and fruit intake, they ‍were rather weak (OR 0.8 for both) and non significant. There were also weak (non-significant) associations with ‍smoking and alcohol consumption, and no association with H. pylori infection (OR=0.6; 95%CI 0.4-1.0). Infection of ‍H. pylori was associated with various indicators of crowding. ‍     

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.     

CagA status of Helicobacter pylori infection and p53 gene mutations in gastric adenocarcinoma

Infection with Helicobacter pylori (H. pylori) increases stomach cancer risk. Helicobacter pylori strains with the cag pathogenicity island (PAI) induce more severe inflammation in the gastric epithelium and are more strongly associated with stomach cancer risk than strains lacking the PAI. We examined whether the prevalence of somatic p53 mutation in gastric adenocarcinoma differed between subjects with and without infection with CagA(+) (a marker for the PAI) H. pylori strains. DNA from 105 microdissected tumor specimens was analyzed for mutation in exons 5-8 of the p53 gene by polymerase chain reaction-based single-strand conformation polymorphism followed by direct DNA sequencing. Enzyme-linked immunosorbent assays for IgG antibodies against H. pylori and CagA were performed on sera collected 2-31 years prior to cancer diagnosis. Tumors from CagA(+) subjects were significantly more likely to have p53 mutations than tumors from CagA(-) subjects (including H. pylori- and H. pylori(+)/CagA(-)): odds ratio = 3.72; 95% confidence interval, 1.06-13.07 after adjustment for histologic type and anatomic subsite of tumor and age at diagnosis and sex of subjects. Mutations were predominantly insertions and deletions (43%) as well as transition mutations at CpG dinucleotides (33%). The data suggest that CagA(+) H. pylori infection, when compared with CagA(-) infection or the absence of H. pylori infection, is associated with a higher prevalence of p53 mutation in gastric adenocarcinoma.     

Salt Taste Preference,Sodium Intake and Gastric Cancer in China

Aim: The risk factors mostly strongly associated with gastric cancer are gastric bacteria Helicobacter pyloriand diet. By using a case-control study among residents in China, we examined the association between sodiumintake, presence of H,pylori, and gastric cancer risk. Methods: A population-based case-control study including235 cases and 410 controls were used. Potential risk factors of gastric cancer were interview for cases and controlsby questionnaire, salt taste preference was measured for all subjects, and IgG antibodies to H,pylori was usedfor H.pylori infection. Risk measures were calculated using unconditional logistic regression. Results: H.pyloriinfection and smoking increased the risk of gastric cancer, with the OR(95%CI) of 1.91(1.32-2.79) and 1.47(1.05-2.05), respectively. Dietary sodium intake independently increased the risk of gastric cancer. Participants withthe highest sodium intake(>5g/day) had a high gastric cancer risk [OR(95%CI)= 3.78(1.74-5.44)]. Participantswith the salt taste preference at 7.3g/L and ≥14.6g/L showed higher risk of gastric cancer [OR(95%) for 7.3g/Land ≥14.6g/L were 5.36(2.72-10.97) and 4.75(2.43-8.85), respectively]. A significantly interaction was foundbetween salt taste preference and H.pylori infection (p=0.037). Salt taste preference was significantly correlatedwith sodium intake (Correlation coefficient=0.46, p<0.001). Conclusion: Salt taste preference test could be asimple way to evaluate an inherited characteristic of sodium intake, and our study confirms the gastric canceris associated with sodium intake and H.pylori.     

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.     

Helicobacter pylori Infection, Serum Pepsinogen Level and Gastric Cancer: A Case-Control Study in Japan

We conducted a case-control study to evaluate the effect of Helicobacter pylori (HP) infection on the risk of gastric cancer in Tokyo, Japan. The sera at the time of diagnosis from 282 gastric cancer cases and 767 sex- and age-matched cancer-free controls were tested for the presence of anti-HP IgG antibody (HM-CAP ELISA kit) and serum pepsinogen (PG) level (PG I and PG II Riabead). No significant association was observed in all sets [matched odds ratio (OR)=1.04, 95% confidence interval: 0.73–1.49]. In subgroup analyses, however, an association was suggested in females [OR=1.57], a younger population (<50 years) [OR=1.86], early cancer [OR=1.53] and small cancer (<40 mm) [OR=1.55]. Furthermore, we observed a tendency for odds ratios to decrease with an increase in age or cancer growth (depth of tumor invasion and tumor size). Considering that the spontaneous disappearance of HP due to extended mucosal atrophy may lead to these decreasing odds ratios, we applied the conditional logistic model adjusted for the PG I/II ratio as a measure of atrophic gastritis. This analysis showed a positive association with HP infection in all sets [OR=1.69; 1.01–2.81], distal cancer [OR=1.88; 1.07–3.31] and intestinal-type cancer [OR=3.76; 1.39–10.18]. We concluded that the risk of cancer associated with HP infection may be underestimated in studies with cross-sectional exposure because of spontaneous disappearance of HP due to extended mucosal atrophy.     

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.     

Epidemiologic findings on serologically defined chronic atrophic gastritis strongly depend on the choice of the cutoff-value

Chronic atrophic gastritis (CAG), a precursor of intestinal gastric cancer, is mostly ascertained noninvasively by serum pepsinogens in epidemiologic studies. However, serological definitions vary widely. We aimed to investigate the impact of this variation on estimated prevalence of CAG and its association with its main risk factors, age and Helicobacter pylori infection. Serum pepsinogen I and II and antibodies against H. pylori were measured by ELISA among 9,444 women and men aged 50-74 years in a population-based cohort study in Saarland/Germany. Application of the various definitions resulted in a wide range of prevalence estimates of CAG prevalence (2.1%-8.2%, with an outlier of 18.8% for one particular definition) and its associations with age and H. pylori infection (age adjusted odds ratios, OR, for CagA positive H. pylori infection: 0.98-4.48). Definitions of CAG based on both pepsinogen I and the pepsinogen I/II ratio or on the pepsinogen I/II ratio only revealed much clearer associations with both age and H. pylori infection than definitions of CAG based on pepsinogen I only (ORs for H. pylori infection: 1.45-4.48 and 0.86-1.30, respectively). Epidemiologic findings on CAG lack comparability due to the heterogeneity in serologic definitions of CAG. The association of age and H. pylori infection with CAG may be strongly underestimated in studies in which CAG is defined by pepsinogen I only.     

Lifestyle and Anti-Helicobacter pylori Immunoglobulin G Antibody among Outpatients

Since eradication of Helicobacter pylori (H. pylori) is thought to be a preventive measure against stomach cancer, several studies have examined factors associated with the infection. This paper reports the association of the infection with lifestyle factors observed in a hospital-based case-control study. Cases were 140 anti-H. pylori IgG antibody-positive outpatients (75 males and 65 females). Controls were 52 antibody-negative outpatients (22 males and 30 females). Both groups had undergone gastroscopy at Aichi Cancer Center Hospital between February 1995 and February 1997, and lifestyle data collected on the first visit were linked to calculate odds ratios. A strong association was observed with smoking among males; age-adjusted odds ratio (OR)=7.85, 95% confidence interval (CI), 2.03–30.4. Rice breakfast (OR=3.74; 95%CI, 1.30–10.8) and soybean paste soup (every day vs. occasionally, OR=5.24; 95%CI, 1.80–15.2) were also associated with antibody positivity in males, but not in females. In females, pickled Chinese cabbage (≥l/week vs. ≥3/month, OR=2.82; 95%CI, 1.06–7.48) and lettuce (≥ I/week vs. ≤3/month, OR=2.90; 95%CI, 1.09 7.76) were significantly associated with positivity. Multivariate analysis gave similar estimates for the above factors. Although the association between smoking and H. pylori infection has not been detected in past studies of a general population, except one recent one, this study on outpatients suggested a possible association. Smoking may work as a cofactor disturbing incidental eradication of H. pylori by antibacterial agents administered for other reasons.     

Effect of Age on the Relationship between Gastric Cancer and Helicobacter pylori

Helicobacter pylori is thought to be involved in the pathogenesis of gastric cancer, but the time point at which it produces its effects (critical time) is unknown. We measured the serum level of H. pylori antibody in 787 gastric cancer patients and 1007 controls aged 20 to 69. Odds ratios for different gastric cancer types and stages were determined for each 10-year age class. The overall odds ratio for gastric cancer decreased with age, being 7.0 for those aged 20–29, 14.5 for those aged 30–39, 9.1 for those aged 40–49, 3.5 for those aged 50–59, and 1.5 for those aged 60–69 (trend in odds ratios: P < 0.01). However, there was no such age-dependent trend for early diffuse-type cancer; the odds ratios were 12.6, 4.0, 7.2, 6.5, and 18.5 respectively ( P =0.29). Early cancer tended to show higher seroprevalence than advanced cancer, especially in older subjects. No significant difference in seroprevalence was observed between diffuse and intestinal cancers within each age-class. Seroreversion must have occurred in the time interval between the critical time and the diagnosis of the cancer, especially in older patients. The age-dependent relationship between H. pylori and gastric cancer may be due to seroreversion, which itself may be independent of age. This age-independence indicates that prolonged exposure to H. pylori does not increase the magnitude of its influence on gastric carcinogenesis. Possible mechanisms through which H. pylori exerts pathogenic effects are continuous inflammation in adulthood and/or irreversible damage to gastric mucosa in childhood or the teenage years.     

Helicobacter pylori infection and chronic atrophic gastritis among Japanese blood donors: a cross-sectional study

To evaluate an association between Helicobacter pylori (H. pylori) infection and chronic atrophic gastritis (CAG), an established precursor of gastric cancer, we performed a cross-sectional study using IgG antibody against H. pylori and pepsinogens of blood donors in four prefectures in Japan. Although a geographic correlation between the age-adjusted prevalence rates for H. pylori infection and those for CAG was not seen, the age-adjusted odds ratios (OR) of H. pylori infection for CAG were high in each area (around five for men and from four to 12.6 for women). The association between them weakened with advancing age; the ORs in the youngest age group (16–29 yrs) and in the oldest age group (50–64 yrs) were 12.5 and 2.8 for men, and 11.5 and 5.2 for women, respectively. These findings suggest that H. pylori infection is strongly associated with CAG, while there are some other factors interacting in the development of CAG. A prospective cohort study in which CAG and H. pylori infection are taken into account will be necessary to assess the risks of gastric cancer.This work was supported in part by a Grant-in-Aid for Cancer Research from The Ministry of Education, Science and Culture of Japan.     

Genetic factors involved in the development of Helicobacter pylori-related gastric cancer

Developmental process to gastric cancer by Helicobacter pylori infection consists of three steps: (1) H. pylori infection; (2) gastric atrophy development; and (3) carcinogenesis. In each step, genetic traits may influence the process, interacting with lifestyle. In the step of H. pylori infection, two lines of genetic polymorphisms were assumed: one influencing gastric acid inhibition interacting with smoking, and the other concerning innate immune response attenuation. The former includes functional polymorphisms of IL-1B (C-31T or tightly linked T-511C), and TNF-A (T-1031C and C-857T), and the latter possibly includes NQO1 C609T. In the step to gastric atrophy, polymorphisms pertaining to the signal transduction from cytotoxin-associated gene A (PTPN11 A/G at intron 3) and to T-cell responses (IL-2 T-330G and IL-13 C-1111T) were hypothesized. There are a limited number of epidemiological genotype studies on the final step of literal carcinogenesis, potentially interacting with smoking, a low vegetable and fruit intake, and salty foods, the well-documented risk factors. In past case-control studies on the associations between genotype and gastric cancer risk, the cases consisted of H. pylori-related and unrelated gastric cancer patients and the controls consisted of individuals including the uninfected (H. pylori unexposed and exposed) and the infected with and without gastric atrophy. Accordingly, it was not clear whether the observed risk was for H. pylori-related or -unrelated gastric cancer, nor which step was involved in the observed associations even when nearly all cases were H. pylori-related. In order to elucidate the genetic traits of H. pylori-related gastric cancer, stepwise evaluation will be required.     

Evaluation of dietary and life-style habits of patients with gastric cancer: a case-control study in Turkey

Objective: Gastric cancer is an important public health problem in the world and Turkey. In addition toHelicobacter pylori (H. pylori), smoking, alcohol consumption and family history, certain dietary factors havebeen associated with its occurrence. The impact of dietary habits and life-style factors on the risk of gastriccancer in Turkey were evaluated in this study. Design: A questionnaire was applied to 106 patients with gastricadenocarcinoma and 106 controls without cancer matched for age (range 28-85 years) and gender selected froma hospital based population. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated withlogistic regression analysis. Results: The incidence of H. pylori was 81.3% in patients. Frequent consumption ofsalty dishes, very salty foods like pickles, soup mixes, sausages, foods at hot temperature (ORs = 3.686, 7.784,5.264, 3.148 and 3.273 respectively) and adding salt without tasting (OR = 4.198) were associated with increasedgastric risk. Also heavy smoking and high amount of alcohol consumption (p = 0.000) were risk factors. Frequentconsumption of green vegetables, onion, garlic and dried fruits (ORs = 0.569, 0.092, 0.795 and 0.041) was nonsignificantlyassociated with decreased risk. Conclusion: Improved dietary habits, reducing salt consumptionand eradication of H. pylori infection may provide protection against gastric cancer in Turkey.     

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.     

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.     

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, relativelyfew studies have investigated on which step smoking has effects in Helicobacter pylori (H. pylori) related gastriccarcinogenesis. In this study we investigated the association of smoking with risk of three steps leading to gastriccancer: H. pylori infection, gastric atrophy, and gastric cancer. Among the participants who visited Aichi CancerCenter Hospital from year 2001 to 2005, 583 cases diagnosed as gastric cancer and age-and sex-frequency-matched1,742 cancer free controls were sampled, from whom those without serum samples or without information aboutsmoking habit were excluded, leaving 576 cases and 1,599 controls eligible for the analyses. Anti- H. pylori IgGantibody and serum pepsinogens (PG) were measured to detect H. pylori infection and gastric atrophy. Smokingstatus was asked by a self-administered questionnaire. The odds ratio (OR) of H. pylori infection, as well as theOR of gastric atrophy among the H. pylori seropositive controls was not significant for smokers. The age- andsex-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 currentsmokers, relative to never smokers. This study revealed that smoking behavior contributed to the increased riskof gastric carcinogenesis from gastric atrophy, and had little influence on H. pylori infection or gastric atrophydevelopment.     

Gastric adenocarcinoma and Helicobacter pylori infection.

Helicobacter pylori infection, thought to be causally related to chronic gastritis, may also be associated with an increased risk of gastric cancer. To determine whether an association with gastric cancer does exist, we retrospectively evaluated serum samples from 69 patients with histologically confirmed gastric adenocarcinoma (32 with cancer at the cardia and 37 with cancer at other sites) and from 218 patients with one of three categories of nongastric cancers, with other gastric cancers, or with benign gastric neoplasms. These samples were compared with samples from 252 cancer-free control subjects, a group comprising 76 asymptomatic volunteers and 176 persons with nonmalignant disorders. Serum samples collected from cancer patients prior to surgery and from cancer-free controls were tested for antibodies to H. pylori by using a highly sensitive and specific IgG enzyme-linked immunosorbent assay. The risk of H. pylori infection in the case patients relative to the control subjects was estimated with the use of multivariate logistic regression analysis to adjust for potential confounding variables. Antibodies to H. pylori were detected in 65% of the patients with noncardia gastric cancer but in only 38% of the patients with gastric cancer located at the cardia. A significant association was found between H. pylori infection and noncardia gastric cancer (odds ratio = 2.67; 99% confidence interval = 1.01-7.06). Within the subset of patients with noncardia gastric cancer, a statistically nonsignificant tendency existed for those with the intestinal versus the diffuse histologic type of noncardia gastric cancer to have a higher risk of H. pylori infection. Our results support the hypothesis of a relationship between H. pylori infection and the development of noncardia gastric adenocarcinoma.     

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.     

Induction of glandular stomach cancers in Helicobacter pylori-infected Mongolian gerbils by 1-nitrosoindole-3-acetonitrile

Helicobacter pylori (H. pylori) infection and high intake of various traditional salt-preserved foods are regarded as risk factors for human gastric cancer. We previously reported that Chinese cabbage contains indole compounds, such as indole-3-acetonitrile, a mutagen precursor. 1-Nitrosoindole-3-acetonitrile (NIAN), formed by the treatment of indole-3-acetonitrile with nitrite under acidic conditions, shows direct-acting mutagenicity. In the present study, NIAN administration by gavage to Mongolian gerbils (MGs) at the dose of 100 mg/kg two times a week resulted in three adduct spots (1.6 adducts/10(8) nucleotides in total), detected in DNA samples from the glandular stomach by (32) P-postlabeling methods. Treatment with six consecutive doses of 100 mg/kg of NIAN, two times a week for 3 weeks, induced well-and moderately-differentiated glandular stomach adenocarcinomas in the MGs at the incidence of 31% under H. pylori infection at 54-104 weeks. Such lesions were not induced in MGs given broth alone, broth + NIAN or infection with H. pylori alone. Thus, endogenous carcinogens formed from nitrosation of indole compounds could be critical risk factors for human gastric cancer development under the influence of H. pylori infection.     

Geographic association of Helicobacter pylori antibody prevalence and gastric cancer mortality in rural China

To examine the geographic association between Helicobacter pylori infection and gastric cancer, we have assessed the prevalence of IgG antibodies to H. pylori in plasma samples taken in 1983 from 1882 men, aged 35-64 years, in 46 rural counties of the People's Republic of China. The gastric cancer mortality rates in these countries in 1973-75 varied from 3 per 1,000 (cumulative rate, 0-64 years) to 69 per 1,000, while the proportions of the population positive for H. pylori antibodies (based on an average of about 41 men per county) varied from 28% to 96%. After correction for the limited number of blood samples per county, the estimated correlation between H. pylori antibody prevalence and gastric cancer mortality was 40% (p = 0.02). No other type of cancer showed a significant association with H. pylori.