| This dissertation is composed of three independent studies: (1) To assess the relationship between absence of H. pylori infection and development of esophageal adenocarcinoma, we conducted a nested case-control study among 128,992 members of an integrated health care system who had participated in a multiphasic health checkup between 1964 and 1969. During follow-up, 52 patients developed esophageal adenocarcinoma. Subjects with H. pylori infection were less likely than uninfected subjects to develop esophageal adenocarcinoma [odds ratio (OR) 0.37, CI (0.16--0.88)]. This significant association was restricted to case-control sets younger than 50 years at enrollment [OR 0.20, 95% CI (0.06--0.68)]. OR were similar for CagA positive and CagA negative H. pylori infection. Body mass index greater than 25 and cigarette smoking were strong independent risk factors for esophageal adenocarcinoma. (2) To evaluate the sensitivity and specificity of the blood Quininium Resin Test (bQRT) for hypochlorhydria against pH monitoring, twelve fasting adult volunteers---seven with and five without H. pylori infection---ingested 80mg/kg of quininium resin twice, with and without acid suppression. The bQRT levels were compared to gastric pH, controlling for omeprazole use and H. pylori infection. Using a bQRT level of 10 as a cutoff for hypochlorhydria, the sensitivity and specificity of the bQRT were 100% and 37.5%, respectively. However, the bQRT predicted omeprazole use more accurately than pH monitoring. (3) To investigate the role of sex as a risk factor for H. pylori infection, a meta-analysis of population-based seroprevalence surveys was undertaken. In adult populations, the test of heterogeneity was non significant and male gender was significantly associated with H. pylori infection (summary OR 1.16 [95%CI 1.11--1.22]). In pediatric populations, the test of heterogeneity was of borderline significance, and the summary OR computed using a random effect model was close to 1 (summary OR 1.03 [95%CI, 0.91--1.17]). Differential antibiotic exposure or differential protective immunity between genders may explain the different results observed between children and adult studies.; These three projects---which span the spectrum of epidemiologic designs (observational study, clinical trial, and meta-analysis), data sources, and analytic methods---reflect a broad application of principles of infectious diseases epidemiology. |
