Folic acid for the prevention of colorectal adenomas - A randomized clinical trial
Folic acid for the prevention of colorectal adenomas - A randomized clinical trial
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DOI：
10.1001/jama.297.21.2351
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发表时间：
2007-06-06
影响因子：
120.7
通讯作者：
Greenberg, E. Robert
中科院分区：
文献类型：
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作者：
Cole, Bernard F.;Baron, John A.;Greenberg, E. Robert
实验室和流行病学数据表明，叶酸可能对大肠有抗肿瘤作用。目的评价补充叶酸预防结直肠腺瘤的安全性和有效性。设计、环境和参与者：1994年7月6日至2004年10月1日期间在9个临床中心进行的一项双盲、安慰剂对照、双因素、3期随机临床试验。参与者包括1021名近期有结直肠腺瘤病史且没有浸润性大肠癌病史的男性和女性。干预参与者按1:1的比例随机分配，接受1mg /d叶酸（n= 516）或安慰剂（n= 505），并分别随机接受阿司匹林（81或325 mg/d）或安慰剂。随访包括2个结肠镜监测周期（第一次间隔为3岁，第二次间隔为3或5年后）。主要结局指标主要结局指标为至少1例结直肠腺瘤的发生。次要结果是发生晚期病变（类似于25%的绒毛特征，高度发育不良，大小类似于1厘米，或浸润性癌症）和腺瘤多样性（0,1 -2，或类似于3个腺瘤）。结果在前3年中，987名参与者（96.7%）接受了结肠镜随访，叶酸组（n= 221）和安慰剂组（n= 206）至少1个结直肠腺瘤的发生率分别为44.1%和42.4%(未调整风险比[RR]， 1.04； 95%可信区间[CI]， 0.90-1.20； P=。58)。叶酸组至少1个晚期病变的发生率为11.4% (n= 57)，安慰剂组为8.6% (n= 42)(未校正RR， 1.32; 95% CI, 0.90-1.92； P=。15)。共有607名参与者（59.5%）接受了第二次随访，叶酸组（n= 127）至少1个结直肠腺瘤的发生率为41.9%，安慰剂组（n= 113）为37.2%(未调整RR， 1.13; 95% CI, 0.93-1.37； P=。23);叶酸组至少1个晚期病变的发生率为11.6% (n= 35)，安慰剂组为6.9% (n= 21)(未调整RR， 1.67; 95% CI, 1.00-2.80； P=。05)。叶酸与患有3个或更多腺瘤和非结直肠癌的高风险相关。性别、年龄、吸烟、饮酒、体重指数、基线血浆叶酸或阿司匹林分配没有显著影响。结论叶酸1 mg/d不能降低结直肠腺瘤的风险。需要进一步的研究来调查叶酸补充剂是否可能增加结直肠肿瘤的风险。
Context Laboratory and epidemiological data suggest that folic acid may have an antineoplastic effect in the large intestine. Objective To assess the safety and efficacy of folic acid supplementation for preventing colorectal adenomas. Design, Setting, and Participants A double-blind, placebo-controlled, 2-factor, phase 3, randomized clinical trial conducted at 9 clinical centers between July 6, 1994, and October 1, 2004. Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma. Intervention Participants were randomly assigned in a 1: 1 ratio to receive 1 mg/d of folic acid ( n= 516) or placebo ( n= 505), and were separately randomized to receive aspirin ( 81 or 325 mg/d) or placebo. Follow-up consisted of 2 colonoscopic surveillance cycles ( the first interval was at 3 years and the second at 3 or 5 years later). Main Outcome Measures The primary outcome measure was occurrence of at least 1 colorectal adenoma. Secondary outcomes were the occurrence of advanced lesions (similar to 25% villous features, high-grade dysplasia, size similar to 1 cm, or invasive cancer) and adenoma multiplicity ( 0, 1-2, or similar to 3 adenomas). Results During the first 3 years, 987 participants ( 96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1% for folic acid ( n= 221) and 42.4% for placebo ( n= 206) ( unadjusted risk ratio [ RR], 1.04; 95% confidence interval [ CI], 0.90-1.20; P=. 58). Incidence of at least 1 advanced lesion was 11.4% for folic acid ( n= 57) and 8.6% for placebo ( n= 42) ( unadjusted RR, 1.32; 95% CI, 0.90-1.92; P=. 15). A total of 607 participants ( 59.5%) underwent a second follow-up, and the incidence of at least 1 colorectal adenoma was 41.9% for folic acid ( n= 127) and 37.2% for placebo ( n= 113) ( unadjusted RR, 1.13; 95% CI, 0.93-1.37; P=. 23); and incidence of at least 1 advanced lesion was 11.6% for folic acid ( n= 35) and 6.9% for placebo ( n= 21) ( unadjusted RR, 1.67; 95% CI, 1.00-2.80; P=. 05). Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers. There was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate, or aspirin allocation. Conclusions Folic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia.