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

Abstract

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 ...

Risk Factors Associated with the Development of Intestinal Metaplasia in First-Degree Relatives of Gastric Cancer Patients

“…Although the exact reason for this clustering pattern remains elusive, we believed that environmental factors, particularly H. pylori infection and childhood living conditions, play an important role. Chang et al (22) reported that the prevalence of H. pylori infection was substantially higher in individuals with a history of gastric cancer in the siblings (adjusted OR, 5.3) when compared with those with parental history of gastric cancer (adjusted OR, 1.7) In our study, we noted that individuals living in rural areas and without in-house tap water supply in childhood had a higher risk of developing intestinal metaplasia. Moreover, the prevalence of intestinal metaplasia in the stomach tended to increase with the number of siblings in the family.…”

“…Because family members are generally considered to be at higher risk of harboring premalignant gastric lesions, it may account for the lower OR reported in this study than previous studies that used general population as controls (16,22).…”

Familial risk for gastric carcinoma: an updated study from Sweden

“…The high sibling risks may be owing to shared childhood environmental factors or to a recessive mode of inheritance, or both. A recent study by Chang et al (2002) showed that the prevalence of H. pylori infection was 89% when a sibling had a history of gastric cancer, giving an OR was 5.3; this was higher than the OR of 2.1 when a parent presented with gastric cancer. Thus subjects who had a sibling with gastric cancer had a higher risk of H. pylori infection than subjects with a parental history of gastric cancer.…”

Helicobacter pylori infection, but not genetic polymorphism of CYP2E1, is highly prevalent in gastric cancer patients younger than 40 years

“…Familial aggregation was reported to be specifi c for the intestinal type of gastric cancer in a patient with a positive family history [33]. Intrafamilial clustering of H. pylori infection was reported to have a crucial role in familial aggregation of gastric cancer [34].…”