Abstract
Objective
To assess the effects of
Helicobacter pylori
treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer.
Design
Blinded randomized placebo controlled trial.
Setting
Linqu County, Shandong province, China.
Participants
3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to
H pylori
were randomly assigned to
H pylori
treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107
H pylori
seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design.
Interventions
H pylori
treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003).
Main outcome measures
Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease.
Results
151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of
H pylori
treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for
H pylori
treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of
H pylori
treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease.
Conclusions
H pylori
treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years.
H pylori
treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer.
Trial registration
ClinicalTrials.gov
NCT00339768
.
Mass eradication of Helicobacter pylori to reduce gastric cancer incidence and mortality: a long-term cohort study on Matsu Islands
