Catherine de Martel

Helicobacter pylori Infection and the Risk of Development of Esophageal Adenocarcinoma

BACKGROUND An increase in the incidence of esophageal adenocarcinoma has coincided with a decrease in the prevalence of Helicobacter pylori infection. Whether these 2 phenomena are associated is unknown. METHODS We conducted a nested case-control study of 128,992 members of an integrated health care system who had participated in a multiphasic health checkup (MHC) during 1964-1969. During follow-up, 52 patients developed esophageal adenocarcinoma. Three randomly chosen control subjects from the MHC cohort were matched to each case subject, on the basis of age at the MHC, sex, race, and the date and site of the MHC. Data on cigarette smoking, alcohol consumption, body mass index (BMI), and education level were obtained at the MHC. Serum samples collected at the MHC were tested for IgG antibodies to H. pylori and to the H. pylori CagA protein. RESULTS Subjects with H. pylori infections were less likely than uninfected subjects to develop esophageal adenocarcinoma (odds ratio [OR], 0.37 [95% confidence interval (CI), 0.16-0.88]). This significant association was restricted to case subjects and control subjects <50 years old at the MHC (OR, 0.20 [95% CI, 0.06-0.68]). In patients with H. pylori infections, the OR for those who tested positive for IgG antibodies to the CagA protein was similar to that for those who tested negative for it. BMI >/=25 and cigarette smoking were strong independent risk factors for development of esophageal adenocarcinoma. CONCLUSION The absence of H. pylori infection, independent of cigarette smoking and BMI, is associated with a markedly increased risk of development of esophageal adenocarcinoma.

Helicobacter pylori Infection and Development of Pancreatic Cancer

Background: Infection with Helicobacter pylori is an established risk factor for gastric cancer. Results from two studies suggest that it may also be a risk factor for pancreatic cancer. Methods: We conducted a nested case control study among 128,992 adult subscribers to the Kaiser Permanente Medical Care Program who had been enrolled in a multiphasic health checkup from 1964 to 1969. Serum collected during the checkup was maintained frozen, and subjects were followed for cancer. Cases consisted of 104 randomly selected subjects among 507 who developed pancreatic cancer in the cohort. Controls consisted of 262 pancreatic cancer–free subjects from a pool of 730 controls previously tested for studies conducted on this cohort. Controls were individually matched to cases on age, gender, race, site, and date of multiphasic health checkup. Control sera were compared with cases for antibodies to H. pylori and the CagA protein. The effects of smoking, alcohol consumption, obesity, and years of education were also investigated. Results: Neither H. pylori [odds ratio (OR), 0.85; 95% confidence interval (95% CI), 0.49-1.48] nor its CagA protein (OR, 0.96; 95% CI, 0.48-1.92) was associated with subsequent development of pancreatic cancer. Smoking (OR, 2.09; 95% CI, 1.17-3.74) and greater number of years of education (OR, 2.13; 95% CI, 1.23-3.69) were risk factors for pancreatic cancer, whereas alcohol consumption and obesity were not. Conclusion: Our results suggest that H. pylori infection is not associated with development of pancreatic cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1188–94)

Serum Ghrelin Levels and Risk of Subsequent Adenocarcinoma of the Esophagus

OBJECTIVE:Several large studies have shown a negative association between Helicobacter pylori (H. pylori) infection and esophageal adenocarcinoma. Diminution of gastric ghrelin secretion by H. pylori could protect against esophageal malignancy by decreasing appetite, food intake, and acid production, thereby decreasing weight and gastroesophageal reflux.METHODS:We evaluated the association of ghrelin with esophageal adenocarcinoma using a population from a previous nested case-control study. Among 128,992 enrolled in a multiphasic health checkup (MHC) between 1964 and 1969, 52 patients developed esophageal adenocarcinoma by the year 2000. Three random controls from the MHC cohort were matched to each case by age, sex, race, and the date and site of their MHC. Serum samples collected at the MHC had been previously tested for IgG antibodies against H. pylori and the CagA protein. Serum ghrelin concentrations were determined by a commercial EIA on 52% of the initial subjects (31 cases and 79 controls).RESULTS:A concentration of ghrelin greater than 3,200 pg/mL at MHC (fourth quartile) was associated with a lower risk of esophageal cancer (H. pylori and body mass index [BMI] adjusted OR = 0.18 [CI 0.04–0.78]). This inverse association was seen only in overweight subjects (BMI ≥ 25, P value for interaction = 0.09). The effects of H. pylori and ghrelin were independent.CONCLUSION:Contrary to the original hypothesis, high rather than low serum ghrelin was associated with protection against esophageal adenocarcinoma but only among overweight subjects.

Opisthorchis viverrini , Clonorchis sinensis and Cholangiocarcinoma

Opisthorchis viverrini ( O. viverrini ) and Clonorchis sinensis ( C. sinensis ) are trematode liver flukes, members of the Opisthorchiidae family, found in specific endemic areas in Eastern Asia and the Russian Federation. Both species are similar in morphology, life cycle, and mode of transmission, which is mainly through the traditional consumption of raw or undercooked freshwater fish. After years of chronic infection, the damage caused by the parasites may lead to bile duct cancer cholangiocarcinoma, the second most common primary liver cancer after hepatocellular carcinoma with very poor prognosis. Although highly effective treatment exists, reinfection is frequent, and prevention using information, education, and communication or environmental control remains challenging.

Validation of the blood quininium resin test for assessing gastric hypochlorhydria

Although gastric hypochlorhydria is a risk factor for gastroenteritis and for gastric cancer, no reliable, inexpensive, noninvasive test exists for screening or epidemiologic studies. We aimed 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 80 mg/kg of quininium resin twice, once with and once without acid suppression. Gastric pH was monitored for 75 minutes; serum samples were obtained at times 0 and 75 minutes. The bQRT levels were compared to gastric pH, controlling for omeprazole use and H. pylori infection. Subjects with a median recorded pH ≥3.5 were considered hypochlorhydric. Using a bQRT level of 10 as a cutoff for hypochlorhydria, the sensitivity and specificity of the bQRT were 100% and 37.5%, respectively. The bQRT predicted omeprazole use more accurately than pH monitoring. In conclusions, The bQRT has a high sensitivity for hypochlorhydria, making it potentially useful in populations with a high prevalence of hypochlorhydria. In its current formulation, the bQRTs low specificity makes it less useful in low-risk population.