K-ras mutations and cell kinetics in Helicobacter pylori associated gastric intestinal metaplasia: a comparison before and after eradication in patients with chronic gastritis and gastric cancer

BACKGROUND: Helicobacter pylori related gastric intestinal metaplasia (IM) is considered to be a precancerous lesion. AIMS: To identify the effects of H pylori eradication on K-ras mutations, cell kinetics in IM and histological changes in patients with and without gastric cancers in a one-year prospective study. METHODS: Patients included group A (n = 39), chronic gastritis, and group B (n = 53), intestinal-type early gastric cancer patients who had all undergone endoscopic mucosal resection (n = 25) or surgical resection (n = 28). K-ras codon 12 mutations in IM were examined, followed by DNA sequencing analysis. Proliferating and apoptotic cells were detected with anti-Ki-67 antibody and using the TUNEL method, respectively. RESULTS: The incidence of K-ras mutations in the cancer was only 3.8%. The mutant K-ras in IM was observed more frequently in group A (46.2%) than in group B patients (1.9%) (p<0.005). After eradication, the K-ras mutations significantly declined to 12.8% in group A (p<0.005). The mutation pattern of K-ras codon 12 before eradication was that GGT was mainly changed to AGT (50%) in group A. AGT transformation was not affected by treatment. Apoptosis in IM showed an increase after H pylori eradication in both groups (p<0.05 in group A) although no histological improvement in IM was observed. The monocyte score was significantly higher in group A than in group B (p<0.05); the score improved significantly after eradication. CONCLUSIONS: K-ras mutations in IM do not always play a role in gastric carcinogenesis but cell kinetics, especially apoptosis, in IM may contribute to it. There are early events in K-ras mutations which are influenced by H pylori infection; some mutations may also be selected by eradication. These unstable K-ras mutations in IM may be related to lymphocyte infiltration caused by H pylori infection.     

Use of Helicobacter pylori-specific antibodies in the evaluation of intestinal metaplasia and gastric dysplasia

It is believed that Helicobacter pylori acts mainly during the initial phases of gastric carcinogenesis. Therefore, this study aims to assess the usefulness of H. pylori diagnosis in patients with chronic gastritis (CG), intestinal metaplasia (IM) and dysplasia--conditions that are associated with gastric cancer. A cross-sectional study of 94 patients was performed, which involved endoscopic biopsy and determination of specific serum anti-H. pylori antibodies (IgA, IgG and IgM) by enzyme-linked immunosorbent assay (ELISA). Biopsies were taken from the gastric antrum and corpus, and from endoscopic lesions. Two specimens per patient were used for bacterial culture. H. pylori infection status, used as the gold standard, was based on culture results. Validity measures were determined and receiver operating curve (ROC) was used to determine the best cut-off for serum antibody levels. Histopathological evaluation (n = 160) was performed independently by two pathologists. Lesions consistent with CG were found in 86 patients (91%), consistent with IM in 69 patients (73%) and with dysplasia in five patients (5%). In the 86 patients with CG, 38 (44%) were infected by H. pylori, as were 26 (38%) and one (20%) with IM and dysplasia, respectively (P=0.039). Area under the curve (AUC) was 0.40 (95% confidence interval [CI]: 0.28-0.51) for IgM, 0.69 (0.58-0.80) for IgA and 0.83 (0.74-0.92) for IgG for the diagnosis of H. pylori infection. Best cut-off was 41 u/mL for IgG, with a sensitivity (95% CI) of 90% (84-96%) and a negative predictive value (NPV) of 91% (85-97%). For IgA the results were 22 u/mL, 74% (65-83%) and 77% (68-86%), respectively. Prevalence of H. pylori appeared to decrease with increasing severity of the gastric lesion. In conclusion, it is suggested that non-invasive serological evaluation of anti-H. pylori (IgG) status after eradication therapy for peptic ulcer disease could be extended, after proper assessment of cut-off values and their validation, to the follow-up of patients with CG and IM.     

Cyclooxygenase-2 expression in Helicobacter pylori-associated premalignant and malignant gastric lesions

Expression of cyclooxygenase-2 (COX-2) in various stages of the Helicobacter pylori-associated gastric carcinogenesis pathway has not been elucidated. We investigated the distribution and intensity of COX-2 expression in premalignant and malignant gastric lesions, and monitored the changes after H. pylori eradication. Gastric biopsies from H. pylori-infected patients with chronic active gastritis, gastric atrophy, intestinal metaplasia (IM), gastric adenocarcinoma, and noninfected controls were studied. Expression of COX-2 was evaluated by immunohistochemistry and in situ hybridization. Endoscopic biopsies were repeated 1 year after successful eradication of H. pylori in a group of IM patients for comparing COX-2 expression and progression of IM. In all H. pylori-infected patients, COX-2 expression was predominantly found in the foveolar and glandular epithelium and, to a lesser extent, in the lamina propria. In the noninfected group, only 35% of cases demonstrated weak COX-2 expression. Intensity of COX-2 was not significantly different between the chronic active gastritis, gastric atrophy, IM, and gastric adenocarcinoma groups. In 17 patients with IM, COX-2 expressions in the epithelial cells and stromal cells were reduced 1 year after H. pylori eradication. However, the changes in COX-2 expression did not correlate with progression/regression of IM. Both premalignant and malignant gastric lesions demonstrate strong COX-2 expression. Successful eradication of H. pylori leads to down-regulation of COX-2 expression but failed to reverse IM at 1 year.     

Evaluation of apoptosis along with BCL-2 and Ki-67 expression in patients with intestinal metaplasia

The primary aim is to compare individuals with intestinal metaplasia (IM), chronic active gastritis (CAG), and normal gastric mucosa (NGM) in terms of apoptosis, proliferation, and Bcl-2 expression. The secondary aim is to determine whether these parameters are different between patients with and without gastric cancer in first-degree relatives. We enrolled 106 patients whose histopathological results were consistent with IM (n: 42), CAG (n: 51), or NGM (n: 13). Antral biopsies were immunohistochemically stained for Bcl-2 and Ki-67 expression. Apoptosis was detected using TUNEL assay. While no significant difference was determined between three groups with regard to apoptosis and Bcl-2 expression (p>0.05), Ki-67 expression was significantly higher in the IM group when compared with the CAG and NGM groups (29.90±22.87 vs. 18.18±16.22 vs. 18.54±20, respectively; p=0.012). Helicobacter pylori was determined to increase apoptosis (49.3% vs. 25.7%, p<0.05), nevertheless, it had no significant effect on proliferation and Bcl-2 expression. Bcl-2 and Ki-67 expression and apoptosis were not different among patients with and without a history of gastric cancer in first degree relatives. Although intestinal metaplasia cases demonstrate an increase in proliferation, no elevation is observed in apoptosis. This can be an important factor in the progression to gastric cancer.     

Type or extension of intestinal metaplasia and immature/atypical "indefinite-for-dysplasia" lesions as predictors of gastric neoplasia

At present, no information exists on the neoplastic potential of the immature hyperproliferative and atypical lesions of the gastric mucosa, which have been recently labeled "indefinite for dysplasia." In addition, uncertainties still exist concerning the risk contribution of intestinal metaplasia (IM) type and extension, as well as Helicobacter pylori infection. In this study, 471 dyspeptic patients showing IM 10% or higher (median, 40; 25th-75th percentile, 20-60) in antral, angulus, or corpus endoscopic biopsies were submitted to repeated examinations (median, 3; 2-5) over 52 (26-85) months of follow-up, during which 44 neoplastic cases were recorded. IM extension, incomplete, sulfomucin-positive, or CAR5 antigen-positive IM; H pylori infection; and indefinite-for-dysplasia lesions (IDLs), as found at first examination, all showed significant neoplastic potential. However, only IDL, ongoing H pylori infection, and patient's age retained independent predictive power in a multivariate model. On the other hand, IM extension 20% or higher proved to be more sensitive as first screening parameter for identification of subjects with increased neoplastic risk. We suggest that patients with IM, when infected, should undergo H pylori eradication to reduce their cancer risk; only those bearing IDL or very extensive IM (which strongly correlates with IDL) should be followed up with endoscopies and biopsies.     

不同年龄组人群胃粘膜病变的观察(3258例胃非恶性肿瘤标本的分析研究)

本文对我国3258例非胃恶性肿瘤标本不同年龄组人群的胃粘膜良性病变进行了观察,发现CSG、CAG、IM、ATP(异型增生)、胃和十二指肠溃疡的检出率均随年龄增长有增高的趋势,高发年龄除CSG为30～39岁外,余者均为40～49岁,此与我国胃癌高发年龄(50～59岁)相比均提前10～20年,符合文献上记载从癌前状态发展为癌前病变直至癌的所需时间。各种病变检出率为IM1914例(58.75%)、CAG1850例(56.78%)、CSG1356例(41.62%)、GU1335例(40.98%)、DU 1221例(37.48%)。ATP1113例(34.16%)。在CAG中IM和ATP均高,在伴ATP中,肠化型CAG(37.35%)又高于非肠化型(5.72%),因此伴异型肠化的萎缩性胃炎可能与我国胃癌高发密切相关。     

Atrophic gastritis in young children and adolescents

BACKGROUND: Helicobacter pylori associated gastric cancer arises via a multistage process, with atrophic gastritis being the precursor lesion. Helicobacter pylori is typically acquired in childhood, yet little is known of the prevalence of atrophic gastritis in childhood. AIM: To study atrophic gastritis among children from countries with high gastric cancer incidence. METHODS: Sections from topographically mapped gastric biopsy specimens from children undergoing clinically indicated endoscopy in Korea and Colombia were evaluated using visual analogue scales. Atrophy was defined as loss of normal glandular components, including replacement with fibrosis, intestinal metaplasia (IM), and/or pseudopyloric metaplasia of the corpus (identified by the presence of pepsinogen I in mucosa that was topographically corpus but phenotypically antrum). RESULTS: One hundred and seventy three children, 58 from Korea (median age, 14 years) and 115 from Colombia (median age, 13 years), were studied. Helicobacter pylori was present in 85% of Colombian children versus 17% of Korean children (p<0.01). Atrophic mucosa near the antrum-corpus border was present in 16% of children, primarily as pseudopyloric metaplasia (31%, IM; 63%, pseudopyloric metaplasia; 6%, both). The median age of children with corpus atrophy was 15 (range, 7-17) years. CONCLUSION: Gastric atrophy occurs in H pylori infected children living in countries with high gastric cancer incidence. Identification and characterisation of the natural history of H pylori gastritis requires targeted biopsies to include the lesser and greater curve of the corpus, starting just proximal to the anatomical antrum-corpus junction, in addition to biopsies targeting the antrum and cardia.     

Heightened susceptibility to chronic gastritis, hyperplasia and metaplasia in Kcnq1 mutant mice

Increased susceptibility to gastric cancer has been associated with a wide range of host genetic and environmental factors, including Helicobacter pylori infection. Helicobacter pylori infection is postulated to initiate a progression through atrophic gastritis, metaplasia and dysplasia to cancer, and has been associated with reduction of acid output and dysregulation of stomach mucins. Here, we present the characterization of two mouse lines carrying mutant alleles of the gene encoding the Kcnq1 potassium channel, which very rapidly establish chronic gastritis in a pathogen-exposed environment. These mice develop gastric hyperplasia, hypochlorhydria and mucin dysregulation independent of infection. Metaplasia, dysplasia and pre-malignant adenomatous hyperplasia of the stomach have been observed in these Kcnq1 mutant mice, also independent of infection. The data presented here suggest that Kcnq1 mutant mice can be used both as an efficient model for the development of atrophic gastritis after infection and to determine the processes during the later stages of progression to gastric cancer independent of infection. Thus, Kcnq1 mutant mice are a powerful new tool for investigating the connection between acid balance, Helicobacter infection and mucin disruption in the progression to gastric cancer.     

Association of the HLA-DQB*0501, allele of the major histocompatibility complex with gastric cancer in Mexico

Etiology of gastric cancer is related to environmental and host factors, Helicobacter pylori infection is the main environmental factor, but it has been also proposed that some major histocomnpatibility complex genes are related to susceptibility and resistance to develop Helicobacter pylori associated gastric diseases. The aim of this study was to study distribution and frequency of some HLA -DQ genes, among Mexican patients harboring gastric diseases. We studied 20 subjects suffering from gastric cancer and 40 subjects harboring Helicobacter pylori-associated chronic gastritis. Diagnosis was confirmed by biopsy. HLA genotyping was performed by a polymerase chain reaction procedure. Ninety nine healthy individuals were also utilized for comparative purposes. Patients with gastric cancer displayed high frequency of HLA-DQA1*0601 (p = 0.003; OR = 20.9, 95% CI = 2.11-506.2) and HLA-DQB1*0501 alleles, the latter when compared to patients with chronic gastritis (p = 0.04; OR = 3.58, 95% CI = 1.05-12.5) and to healthy individuals (p = 0.002; OR = 4.5, 95% CI =1.59-12.7). According to our results, in addition to Helicobacter pylori infection, there are immunogeneic markers of the HLA-DQ region, which are determinant in confering susceptibility for gastric cancer.     

Helicobacter pylori & gastric disease

Since the discovery of Helicobacter pylori(H. pylori), causal linkage between H. pylori infection and some of gastric disease has been generally accepted from the results of many studies. Indeed the usefulness of H. pylori eradication therapy for acute gastritis, peptic ulcer, gastric polyp and MALT lymphoma etc. has been reported. In the low grade MALT lymphoma, the regression rate by this therapy is about 70%. On the other hand, we should pay the caution to several adverse effects, such as drug resistance and GERD, of H. pylori eradication therapy. However, based on the several results of comparative studies between antibiotic therapy and the other one, the antibiotic therapy for peptic ulcer is only covered by national health insurance at present. The reversibility of gastric precancerous conditions such as mucosal atrophy, intestinal metaplasia and dysplasia by antibiotic therapy has been studied, but its significance is not clear yet. In animal experiment, H. pylori infection induced gastric adenocarcinoma in Mongolian Gerbils. However, this phenomenon is limited to this kind of animal only. To proof the causal link between H. pylori infection and genesis of gastric cancer in human being, clinical intervention trials are ongoing in the world. If these trials can clarify it, the H. pylori eradication therapy will be established as preventive measure for gastric carcinogenesis.     

Diagnostic yield of gastric biopsy specimens when screening for preneoplastic lesions

The Sydney system recommends sites and numbers of stomach biopsies (mapping) for evaluation of Helicobacter pylori-associated lesions. The diagnostic yield of the recommended mapping technique in populations at high risk for gastric preneoplastic lesions has not been established. We evaluated pathology data from 733 endoscopies performed as part of an intervention study that assessed the effects of H. pylori treatment on preneoplastic conditions. Two pathologists assessed whether the mapping sequence of the 7 biopsy specimens obtained during each endoscopy was correctly followed and graded the specimens using the Sydney classification for gastritis. If the mapping sequence was followed, then we evaluated whether the amount of information obtained from 3 biopsy samples approximated that obtained from 5 and 7 biopsy samples. The mapping sequence was followed in only 239 (33%) endoscopies, indicating that experienced endoscopists can inadvertently misidentify sites in the stomach when obtaining specimens. When data from 7 specimens were used, H. pylori was found in 205 endoscopies, atrophy in 152, metaplasia in 135, and dysplasia in 22. When data from 3 specimens were used, the sensitivity was 99% for presence of H. pylori, 82% for atrophy and metaplasia, and 81% for dysplasia. When data from 5 specimens were used, the sensitivity was 100% for H. pylori, 96% for atrophy, and 95% for metaplasia and dysplasia. Although site-specific biopsy mapping is difficult in practice, the recommendations of the Sydney system as to the location and number of gastric biopsy specimens can adequately identify significant gastric histopathology.     

Histologic changes of the gastric mucosa associated with primary gastric lymphoma in endoscopic biopsy specimens

CONTEXT: Recently, we have observed intestinal metaplasia, atrophy, and dysplasia in the mucosa adjacent to primary gastric lymphoma (PGL) in gastrectomy specimens. OBJECTIVE: To determine the frequency and type of epithelial disorders at the histopathologic level in the mucosa adjacent to PGL in endoscopic specimens. DESIGN: We studied 54 endoscopic biopsies from patients harboring PGL. We searched for the following morphologic changes in the gastric mucosa: intestinal metaplasia; atrophy; dysplasia; epithelial erosion; and atypical regeneration of the glandular epithelium. Other nonepithelial findings such as lymphoid follicles, Helicobacter pylori, and lymphoma grade, were also recorded. For comparative purposes, 50 endoscopic biopsies with gastric adenocarcinoma and 50 biopsies with chronic gastritis associated with H pylori infection were also studied. RESULTS: The 54 biopsies included 28 (52%) low-grade and 26 (48%) high-grade PGLs. We found intestinal metaplasia in 32 biopsies (59%), atrophy in 20 biopsies (37%), dysplasia in 2 biopsies (4%), erosion of the epithelium in 33 biopsies (61%), and atypical regenerative changes of the glandular epithelium in 10 biopsies (19%). Lymphoid follicles were found in 21 biopsies (39%), and H pylori was demonstrated in 31 biopsies (57%). When groups were compared, the frequency of epithelial changes in biopsies from patients with PGL and adenocarcinoma was similar. Intestinal metaplasia or atrophy were present in only 10% of biopsies from patients with gastritis, and dysplastic glands were not identified. CONCLUSIONS: Biopsies from patients with PGL showed chronic damage of the gastric mucosa at diagnosis, including precancerous conditions. Intestinal metaplasia and atrophy were among the most frequent disorders, but dysplasia was also occasionally present. Endoscopists and pathologists must be acquainted with such changes and look for them in the initial biopsy, as well in subsequent samples. This practice is particularly important when reviewing biopsies from patients with low-grade mucosa-associated lymphoid tissue (MALT)-lymphomas who are eligible for eradication treatment for H pylori.     

Comparison of magnesium concentration in serum, erythrocytes and gastric tissue in two groups of patients affected by chronic gastritis, Helicobacter pylori negative and positive.

Magnesium seems to be an important factor both for acid gastric secretion regulation (together with Ca2+) and for Helicobacter pylori survival and virulence. It can therefore be useful to evaluate if Helicobacter pylori (HP) infection is accompanied by variations in the host Mg availability. In this study serum, erythrocytary and gastric tissue Mg concentration was measured in 36 patients affected by chronic antral gastritis. Based on the presence of Helicobacter pylori infection, the patients were subdivided in two groups: group A: Helicobacter pylori negative, n = 23; group B: Helicobacter pylori positive, n = 13. Results: While no differences were found between the two groups for serum Mg (group A 0.81 +/- 0.07 mm/L, group B 0.81 +/- 0.11 mm/L), both erythrocytary Mg (EMg) and gastric tissue Mg were found significantly lower in the HP positive subjects (erythrocytary Mg: 2.14 +/- 0.55 vs. 1.81 +/- 0.34 mm/L; gastric tissue Mg: 729.2 +/- 333.8 vs. 510.6 +/- 178.8 microg/g of dried tissue for group A and B respectively, p < 0.001 for both determinations). Erythrocytary Mg reduction is a clue of the whole body reduction in Mg availability (and consequently in gastric cells as well); the erythrocytary Mg reduction detected in the present paper for Helicobacter pylori positive patients can weaken gastric cells by impairing their metabolism. The hypothesis submitted is to impair Mg utilization in Helicobacter pylori, in order to improve eradication treatment, and in the meantime to preserve Mg homeostasis in infected cells.     

Impact of Helicobacter pylori eradication on morphological changes in gastric mucosa

The purpose of the study was to examine gastric mucosal morphological changes in patients with gastroduodenal pathology after eradication therapy for Helicobacter pylori (H. pylori). A hundred and thirty-eight patients (40 females and 98 males) were examined. Of them, there were 122 patients with duodenal peptic ulcer, 8 with gastric peptic ulcer, 5 with erosive gastritis, 2 with chronic atrophic antral gastritis, and 1 with non-atrophic gastritis. Two months and a year after therapy, manifestations of gastric mucosal atrophy, the degree of inflammation, and its activity significantly diminished in patients with complete H. pylori eradication. Positive changes were observed mainly in the antral portion of the stomach. In patients with partial eradication, chronic inflammation and its activity became less. Two months and a year following therapy, positive changes in the gastric mucosa were absent in patients without H. pylori eradication.     

慢性萎缩性胃炎患者Hp 感染与TGF-β、IL-6 和TNF-αRII 的表达研究

目的:探讨慢性萎缩性胃炎患者幽门螺旋杆菌感染与胃黏膜中转化生长因子茁受体域、白介素6 和肿瘤坏死因子琢的表达情况。方法:选取76例慢性萎缩性胃炎(CAG)患者胃黏膜病变组织的胃镜活检标本,采取PCR 荧光法检测Hp 感染情况,免疫组化法检测TGF-βRⅡ、IL-6 和TNF-α在胃小凹上皮和间质炎细胞中的表达。结果:慢性炎症程度在Hp感染阳性组和阴性组中差异有统计学意义(P<0.05);间质炎细胞中IL-6的表达在Hp感染阳性组和阴性组中差异有统计学意义(P<0.05);TGF-βRⅡ、TNF-α的表达在Hp感染阳性组和阴性组中无显著性差异(P>0.05);间质炎细胞中IL-6与慢性炎症程度呈正相关关系(r=0.249,P=0.03);萎缩程度与肠上皮化生严重程度、上皮内瘤变程度呈正相关关系(r=0.697,0.366)。结论:IL-6在间质炎性细胞中的表达与Hp相关性CAG患者的慢性炎症程度有关,慢性萎缩程度促进肠上皮化生和上皮内瘤变的发生。     

Decreased gastric proliferation of foveolar epithelial cells after the eradication of Helicobacter pylori.

Increased epithelial cell proliferation is associated with an increased risk of gastric carcinoma. Helicobacter pylori infection is an established risk factor for gastric cancer and the organism has recently been classified as a group I carcinogen by an IARC working group. In this study, we describe differences in gastric epithelial cell proliferation between a H. pylori eradicated group (n = 21) and a not eradicated group (n = 8) after anti-H. pylori eradication therapy to show that increased cell proliferation is associated with H. pylori infection. H. pylori infection was determined by rapid urease test and immunohistochemical method with anti-H. pylori polyclonal antibody. Gastric epithelial cell proliferation was assessed using immunohistochemical method using Ki-67 monoclonal antibody. Ki-67 positive cells in H. pylori associated chronic active gastritis were observed in the glandular neck and the upper portion of foveolar epithelium. Patients who cleared their H. pylori infections showed a significant decrease of Ki-67 labeling index after therapy (0.73 +/- 0.10 vs. 0.48 +/- 0.08, p < 0.01). By contrast, Ki-67 labeling index before and after treatment in patients who remained positive for H. pylori showed no significant difference (0.78 +/- 0.08 vs 0.74 +/- 0.10, p > 0.05). These results indicate that H. pylori infection increases the proliferation of gastric foveolar epithelium, which is reduced by the eradication therapy. We suggest that anti-H. pylori eradication therapy can prevent mucosal cell proliferation to be closely associated with gastric carcinogenesis.     

Microsatellite instability in gastric intestinal metaplasia in patients with and without gastric cancer

The role and significance of microsatellite instability (MSI) in gastric carcinogenesis remain unknown. This study determined the chronology of MSI in gastric carcinogenesis by examining intestinal metaplasia (IM) from patients with and without gastric cancer. DNA was obtained from gastric specimens of 75 patients with gastric IM (30 cancer, 26 peptic ulcer, and 19 chronic gastritis patients) and was amplified with a set of eight microsatellite markers. Eight (26. 7%) tumors and seven (9.3%) IM samples (three from cancer-free patients) displayed high-level MSI (three or more loci altered). Low-level MSI (one or two loci altered) was detected in 50% of the tumors, in 40% of IM samples coexisting with cancer, and in 38% of IM tissues of cancer-free individuals. Among the 30 cancer patients, microsatellites were more frequently altered in IM coexisting with tumors that showed MSI (P = 0.003). In addition, patients with low-level MSI in the tumor tissues were more likely to have active Helicobacter pylori infection than those with stable tumors (P = 0.02). In conclusion, this study indicates that MSI occurs not only in gastric IM of patients with gastric carcinoma, but also in IM of cancer-free individuals. These data suggest that the progressive accumulation of MSI in areas of IM may contribute to gastric cancer development, representing an important molecular event in the multistep gastric carcinogenesis cascade.     

Seroepidemiology of Helicobacter pylori among adolescents in Taiwan

Helicobacter pylori has been documented to be associated with chronic type B gastritis, peptic ulcer and gastric cancer. In order to examine the seroprevalence and risk factors for Helicobacter pylori infection in Taiwan, a total of 871 adolescents were selected randomly from junior high school children in 20 study precincts and townships. Serum samples collected were tested for IgG antibodies against Helicobacter pylori by enzyme-linked immunosorbent assay using commercial kits. The overall seropositive rate was 21.1% showing no gender difference. There was a striking geographical variation in seroprevalence of Helicobacter pylori infection ranging from 4.6% to 37.1% in 20 precincts and townships. The seroprevalence was highest in the north (25.4%), medium in central Taiwan (21.9%), and lowest in the south (18.7%). The higher the age-adjusted mortality from gastric cancer in a given study area, the higher the seroprevalence of Helicobacter pylori in the area. Metropolitan and aboriginal areas had higher seroprevalences than urban and rural areas, but the difference was not statistically significant. The seroprevalence was higher for those who had no sibling (29.4%) or had a sibship size of > or = 6 (31.1%) than for those with a sibship size of 1-5 (20.0%), but the difference was not statistically significant either.