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Randomized Double-Blind Factorial
Trial of Three Treatments To Reduce the Prevalence of Precancerous
Gastric Lesions
Wei-cheng You, Linda
M. Brown, Lian Zhang, Ji-you Li, Mao-lin
Jin, Yun-shen Chang, Jun-ling Ma, Kai-feng
Pan, Wei-dong Liu, Yuanreng Hu, Susan
Crystal-Mansour, David Pee, William J. Blot,
Joseph F. Fraumeni, Jr., Guang-wei Xu, Mitchell
H. Gail
Affiliations of authors: Peking
University School of Oncology, Beijing Cancer Hospital and Beijing
Institute for Cancer Research, Beijing, China (WY, LZ, JL, MJ, YC, JM,
KP, GX); Division of Cancer Epidemiology and Genetics, National Cancer
Institute, Bethesda, MD (LMB, JFF, MHG); Linqu County Public Health
Bureau, Shandong, China (WL); Westat, Rockville, MD (YH, SCM);
Information Management Services, Rockville, MD (DP); International
Epidemiology Institute, Ltd., Rockville, MD, and Vanderbilt
University, Nashville, TN (WJB)
Correspondence to: Mitchell Gail, MD, PhD, National Cancer Institute,
6120 Executive Blvd., EPS 8032, Bethesda, MD 20892-7244 (e-mail: gailm@mail.nih.gov
).
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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.
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