The effect of folic acid on the development of stomach and other gastrointestinal cancers.
OBJECTIVE
To evaluate the roles of folic acid and beta-carotene in the chemoprevention of gastric and other gastrointestinal (GI) cancers.


METHODS
In a randomized, double-blind, placebo-controlled trial, a total of 216 patients with atrophic gastritis were randomly assigned to one of the four groups: (1) folate (FA, 20 mg per day plus vitamin B(12) 1 mg, intramuscularly, per month for one year, then 20 mg two times a week plus 1 mg per three months for the next year); (2) natural beta-carotene (N-betaC, 30 mg per day for first year, then 30 mg two times a week for the next); (3) synthetic beta-carotene (S-betaC, administered as in N-betaC); and (4) placebo. Follow-ups continued from 1994 to 2001.


RESULTS
A total of 7 new cases of gastrointestinal cancers were diagnosed with 3 stomach, 1 colon and 1 esophageal cancers occurring in the placebo group; 1 stomach cancer in both of the N-betaC and S-betaC groups, and no cancer occurring in FA group. In terms of GI cancers, there was a significant reduction in the FA group, compared with the placebo group (P = 0.04). A similar trend was observed in both N-betaC and S-betaC groups (P = 0.07 - 0.08). Taken together, the three intervention groups displayed a highly significant decrease in occurrence (P = 0.004, vs placebo), and a lower risk for GI cancers (OR = 0.12; 95% confidence interval, 0.03 - 0.51). For development of gastric cancer, any one of the three active-treated groups did not reach statistically significant reduction. The FA group showed obvious improvement of the gastric mucosal lesions with more patients displaying lesions reversed or stable atrophy and inflammation (P = 0.04), reversed intestinal metaplasia (P = 0.06) at the end of follow-up, and reversed displasia (P = 0.017) at 12 months. Two cases of false jaundice were found in beta-carotene groups with no influence on administration, and no side-effects were reported in FA group.


CONCLUSIONS
This trial revealed the interventional effect of folic acid on the development of GI cancers, a similar effect of beta-carotene was also detected. Also, folic acid may be of use to treat atrophic gastritis by preventing or reversing the precancerous lesions.
Zhu
Shunshi
S
Department of Gastroenterology, The Ninth People's Hospital, Shanghai Second Medical University, Shanghai 200011, China.
Mason
Joel
J
Shi
Yao
Y
Hu
Yunbiao
Y
Li
Rongrong
R
Wahg
Min
M
Zhou
Yihe
Y
Jin
Guanqiu
G
Xie
Yuye
Y
Wu
Guiquan
G
Xia
Dehuang
D
Qian
Zhenhua
Z
Sohg
Hailian
H
Zhang
Lidong
L
Russell
Robert
R
Xiao
Shudong
S
D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D005753:Gastric Mucosa / Q000473:pathology; D005770:Gastrointestinal Neoplasms / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D013274:Stomach Neoplasms / Q000517:prevention & control*; D019207:beta Carotene / Q000627:therapeutic use
D016588:Anticarcinogenic Agents; D019207:beta Carotene; D005492:Folic Acid