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.


CONCLUSIONS
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.
You
Wei-cheng
WC
Peking University School of Oncology, Beijing Cancer Hospital and Beijing Institute for Cancer Research, Beijing, China.
Brown
Linda M
LM
Zhang
Lian
L
Li
Ji-you
JY
Jin
Mao-lin
ML
Chang
Yun-shen
YS
Ma
Jun-ling
JL
Pan
Kai-feng
KF
Liu
Wei-dong
WD
Hu
Yuanreng
Y
Crystal-Mansour
Susan
S
Pee
David
D
Blot
William J
WJ
Fraumeni
Joseph F
JF
Xu
Guang-wei
GW
Gail
Mitchell H
MH
D000328:Adult; D000658:Amoxicillin / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage; D002681:China / Q000453:epidemiology; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005163:Factor Analysis, Statistical; D005260:Female; D005737:Garlic; D005773:Gastroscopy; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage; D008517:Phytotherapy; D011230:Precancerous Conditions / Q000453:epidemiology* / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D015995:Prevalence; D012643:Selenium / Q000008:administration & dosage; D012720:Severity of Illness Index; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D014810:Vitamin E / Q000008:administration & dosage
D014810:Vitamin E; D000658:Amoxicillin; D012643:Selenium; D009853:Omeprazole; D001205:Ascorbic Acid