Effects of Helicobacter pylori treatment on gastric cancer incidence and mortality in subgroups.

Among 2258 Helicobacter pylori-seropositive subjects randomly assigned to receive one-time H. pylori treatment with amoxicillin-omeprazole or its placebo, we evaluated the 15-year effect of treatment on gastric cancer incidence and mortality in subgroups defined by age, baseline gastric histopathology, and post-treatment infection status. We used conditional logistic and Cox regressions for covariable adjustments in incidence and mortality analyses, respectively. Treatment was associated with a statistically significant decrease in gastric cancer incidence (odds ratio = 0.36; 95% confidence interval [CI] = 0.17 to 0.79) and mortality (hazard ratio = 0.26; 95% CI = 0.09 to 0.79) at ages 55 years and older and a statistically significant decrease in incidence among those with intestinal metaplasia or dysplasia at baseline (odds ratio = 0.56; 95% CI = 0.34 to 0.91). Treatment benefits for incidence and mortality among those with and without post-treatment infection were similar. Thus H. pylori treatment can benefit older members and those with advanced baseline histopathology, and benefits are present even with post-treatment infection, suggesting treatment can benefit an entire population, not just the young or those with mild histopathology.

Fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality.

In the Shandong Intervention Trial, 2 weeks of antibiotic treatment for Helicobacter pylori reduced the prevalence of precancerous gastric lesions, whereas 7.3 years of oral supplementation with garlic extract and oil (garlic treatment) or vitamin C, vitamin E, and selenium (vitamin treatment) did not. Here we report 14.7-year follow-up for gastric cancer incidence and cause-specific mortality among 3365 randomly assigned subjects in this masked factorial placebo-controlled trial. Conditional logistic regression was used to estimate the odds of gastric cancer incidence, and the Cox proportional hazards model was used to estimate the relative hazard of cause-specific mortality. All statistical tests were two-sided. Gastric cancer was diagnosed in 3.0% of subjects who received H pylori treatment and in 4.6% of those who received placebo (odds ratio = 0.61, 95% confidence interval = 0.38 to 0.96, P = .032). Gastric cancer deaths occurred among 1.5% of subjects assigned H pylori treatment and among 2.1% of those assigned placebo (hazard ratio [HR] of death = 0.67, 95% CI = 0.36 to 1.28). Garlic and vitamin treatments were associated with non-statistically significant reductions in gastric cancer incidence and mortality. Vitamin treatment was associated with statistically significantly fewer deaths from gastric or esophageal cancer, a secondary endpoint (HR = 0.51, 95% CI = 0.30 to 0.87; P = .014).

Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions.

BACKGROUND: Randomized trials have yielded mixed results on the effects of treatment for Helicobacter pylori and little information on the effects of vitamins or garlic supplements on precancerous gastric lesions. We conducted a randomized trial to test the effects of one-time H. pylori treatment and long-term vitamin or garlic supplements in reducing the prevalence of advanced precancerous gastric lesions. METHODS: Most of the adults aged 35-64 years in 13 randomly selected villages in Linqu County, Shandong Province, China, were identified and given baseline endoscopies in 1994. In 1995, 3365 eligible subjects were randomly assigned in a factorial design to three interventions or placebos: amoxicillin and omeprazole for 2 weeks in 1995 (H. pylori treatment); vitamin C, vitamin E, and selenium for 7.3 years (vitamin supplement); and aged garlic extract and steam-distilled garlic oil for 7.3 years (garlic supplement). Subjects underwent endoscopies with biopsies in 1999 and 2003, and the prevalence of precancerous gastric lesions was determined by histopathologic examination of seven standard biopsy sites. The 3365 eligible randomized subjects represented 93.5% of those with baseline endoscopy and included all baseline histologic categories except gastric cancer. Only 0.18% had normal gastric mucosa. Logistic regression was used to estimate the intervention effects on the odds of advanced precancerous gastric lesions, and t-tests were used to assess effects on histologic severity. All statistical tests were two-sided. RESULTS: H. pylori treatment resulted in statistically significant decreases in the combined prevalence of severe chronic atrophic gastritis, intestinal metaplasia, dysplasia, or gastric cancer in 1999 (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.62 to 0.95) and in 2003 (OR = 0.60; 95% CI = 0.47 to 0.75), and had favorable effects on the average histopathologic severity and on progression and regression of precancerous gastric lesions in 2003. H. pylori treatment did not reduce the combined prevalence of dysplasia or gastric cancer. However, fewer subjects receiving H. pylori treatment (19/1130; 1.7%) than receiving placebo (27/1128; 2.4%) developed gastric cancer (adjusted P = .14). No statistically significant favorable effects were seen for garlic or vitamin supplements. CONCLUSION: H. pylori treatment reduces the prevalence of precancerous gastric lesions and may reduce gastric cancer incidence, but further data are needed to prove the latter point. Long-term vitamin or garlic supplementation had no beneficial effects on the prevalence of precancerous gastric lesions or on gastric cancer incidence.

Relation between food reinforcement and dopamine genotypes and its effect on food intake in smokers.

BACKGROUND: Food reinforcement and dopaminergic activity may influence food consumption, but research on whether they interact has not been performed. OBJECTIVE: We assessed the effects of food reinforcement and the interaction of food reinforcement with the dopamine transporter (SLC6A3) genotype and the dopamine D(2) receptor (DRD(2)) genotype on energy consumption. DESIGN: We studied food-consumption and reinforcing-value-of-food tasks in 88 smokers of European ancestry before they enrolled in smoking-cessation treatment. In the food-consumption task, subjects tasted and consumed 8 snack foods ad libitum. The reinforcing-value-of-food task assessed how hard subjects would work for food. RESULTS: Significant interactions between dopamine genotypes and food reinforcement were observed. Subjects high in food reinforcement who lacked an SLC6A3*9 allele consumed significantly more calories (>150 kcal; P = 0.015) than did subjects low in food reinforcement or those high in food reinforcement who carried at least one SLC6A3*9 allele. Similarly, subjects high in food reinforcement who carried at least one DRD(2)*A1 allele consumed >130 kcal more (P = 0.021) than did subjects low in food reinforcement or those high in food reinforcement who lacked a DRD(2)*A1 allele. There was also a main effect of food reinforcement on energy intake (P = 0.005), with subjects high in food reinforcement consuming 104 kcal (or 30%) more than did subjects low in food reinforcement. CONCLUSIONS: Food reinforcement has a significant effect on energy intake, and the effect is moderated by the dopamine loci SLC6A3 and DRD(2).

Food hedonics and reinforcement as determinants of laboratory food intake in smokers.

Both the hedonic ratings and the reinforcing value of food have been considered to be determinants of food intake. The objective of this study was to compare the pleasurable ratings and the reinforcing value of food as determinants of energy intake. Seventy-four smokers were studied in food consumption and reinforcing value of food tasks prior to enrolling in a smoking-cessation treatment program. For the food consumption task, the participants tasted and consumed food ad lib from eight snack foods. The reinforcing value of the food task assessed how hard subjects would work for a preferred snack food. Results showed that food reinforcement was related to laboratory food intake, with those high in food reinforcement consuming significantly more calories (+114.4 kcal, P<.01) than did the participants low in food reinforcement. Food reinforcement was related to food intake for the preferred food as well as to total energy intake. Hedonics for the preferred food was related to food reinforcement but not to either measure of laboratory energy intake. In multiple-regression models, food reinforcement and the interaction of food reinforcement by sex were significant predictors of energy intake for the preferred food and for total energy intake, along with baseline hunger. In conclusion, energy intake in smokers in a laboratory setting is more strongly related to food reinforcement than to the hedonic ratings of food.

Changes in food reward following smoking cessation: a pharmacogenetic investigation.

RATIONALE: Despite the high prevalence and public health significance of weight gain following smoking cessation, little is known about the underlying bio-behavioral mechanisms or effective therapies. OBJECTIVES: We evaluated the effects of bupropion on food reward following smoking abstinence and the moderating influence of genotype. METHODS: Seventy-one smokers of European ancestry were genotyped for the dopamine D2 receptor ( DRD2) Taq1 polymorphism and randomized to treatment with bupropion (300 mg) or placebo for smoking cessation. Subjects participated in two behavioral laboratory sessions during which the rewarding value of food was assessed using a behavioral economics measure: session 1 occurred prior to medication and before cessation of smoking; session 2 occurred following 3 weeks of medication and 1 week of sustained abstinence. RESULTS: Carriers of the DRD2 A1 minor allele exhibited significant increases in the rewarding value of food following abstinence from smoking, and these effects were attenuated by bupropion treatment ( P=0.03 for medication by genotype interaction). Further, higher levels of food reward at session 2 (post-quit) predicted a significant increase in weight by 6-month follow-up in the placebo group, but not in the bupropion-treated group ( P=0.006 for medication by food reward interaction). CONCLUSIONS: These results provide new evidence that the increase in body weight that occurs following smoking cessation is related to increases in food reward, and that food reward is partly determined by genetic factors. Bupropion's efficacy in attenuating abstinence-induced weight gain may be attributable, in part, to decreasing food reward.