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. Gastric cancer is the second most common cause of cancerrelated death in the world. 1 In Korea, gastric cancer is the most frequently diagnosed malignancy, although the associated mortality rate has been decreasing slowly for the past 10 years. 2 About 60% of Korean adults are infected with Helicobacter pylori. 3,4 Such infection is a causative factor in gastric carcinogenesis, and H. pylori infection is associated with a 2-fold increased risk of developing gastric adenocarcinoma. 5,6 A positive family history is also associated with an increased risk of gastric cancer. 7-10 The possible causes of familial aggregation of gastric cancer are common genetic backgrounds and common environmental risk factors including H. pylori infection, excessive intake of salt and N-nitroso compounds and a deficiency of dietary antioxidants among patients with gastric cancer and their family members. Among these risk factors, intrafamilial clustering of H. pylori infection is regarded as a leading cause of gastric carcinogenesis. This association is significantly greater for H. pylori strains that possess the cytotoxin-associated gene cagA, [11][12][13] a key gene of the so-called "pathogenicity island". 14 The first aim of our study was to examine the prevalence of H. pylori infection in offspring and siblings of patients with gastric cancer to evaluate its role in intrafamilial aggregation of gastric cancer. The second aim was to investigate the relationship between CagA or vacuolating cytotoxin (VacA) seropositivity as virulence markers of H. pylori strains and H. pylori infection in relatives of cancer patients. Finally, we examined the frequency of gastric precancerous lesion, atrophic gastritis and/or intestinal metaplasia in the H. pyloriinfected relatives of cancer patients. MATERIAL AND METHODS Recruitment of relatives of cancer patients and controlsFrom November 2000 to March 2002, we recruited subjects who wished to receive routine upper gastrointestinal endoscopy and evaluation ...