The beta-carotene and retinol efficacy trial:: Incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping β-carotene and retinol supplements
The beta-carotene and retinol efficacy trial:: Incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping β-carotene and retinol supplements
复制标题
DOI：
10.1093/jnci/djh320
复制
发表时间：
2004-12-01
期刊：
影响因子：
--
通讯作者：
Williams, JH
中科院分区：
文献类型：
--
作者：
Goodman, GE;Thornquist, MD;Williams, JH
背景：β -胡萝卜素和视黄醇功效试验（CARET）测试了每日β -胡萝卜素（30毫克）和视黄醇棕榈酸酯（25 000国际单位）对18314名因吸烟或接触石棉而有肺癌高风险的参与者肺癌、其他癌症发病率和死亡的影响。CARET于1996年1月提前停止，因为被随机分配接受积极干预的参与者发现，与安慰剂组的参与者相比，肺癌发病率增加28%，死亡率增加17%，心血管疾病死亡率更高。方法：干预结束后，CARET参与者将研究维生素退还给他们的研究中心，并提供最终的血液样本。他们继续每年通过电话和邮件进行自我报告。自我报告的癌症终点通过病理报告确认，死亡终点通过死亡证明确认。所有统计检验均为双侧检验。结果：随访至2001年12月31日，与安慰剂组相比，积极干预组干预后肺癌和全因死亡率的相对危险度分别为1.12（95%可信区间[CI] = 0.97 ~ 1.31）和1.08 （95% CI = 0.99 ~ 1.17）。平滑的肺癌发病率和全因死亡率的相对风险曲线表明，在干预后随访期间，相对风险保持在1.0以上。相比之下，心血管疾病死亡率的相对风险在干预停止后迅速下降到1.0。在干预后阶段，女性的肺癌死亡率（1.33比1.14；P.36）、心血管疾病死亡率（1.44比0.93；P.03）和全因死亡率（1.37比0.98;P = .001）的相对风险高于男性。结论：先前报道的p -胡萝卜素和棕榈酸视黄酯对吸烟者和职业接触石棉的个体肺癌发病率和全因死亡率的不良影响在停止给药后仍然存在，尽管它们不再具有统计学意义。计划亚组分析表明，肺癌的过度风险主要局限于女性，心血管疾病死亡率主要局限于女性和前吸烟者。
Background: The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the effect of daily beta-carotene (30 mg) and retinyl palmitate (25 000 IU) on the incidence of lung cancer, other cancers, and death in 18 314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure. CARET was stopped ahead of schedule in January 1996 because participants who were randomly assigned to receive the active intervention were found to have a 28% increase in incidence of lung cancer, a 17% increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group. Methods: After the intervention ended, CARET participants returned the study vitamins to their study center and provided a final blood sample. They continue to be followed annually by telephone and mail self-report. Self-reported cancer endpoints were confirmed by review of pathology reports, and death endpoints were confirmed by review of death certificates. All statistical tests were two-sided. Results: With follow-up through December 31, 2001, the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 (95% confidence interval [CI] = 0.97 to 1.31) and 1.08 (95% CI = 0.99 to 1.17), respectively. Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up. By contrast, the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped. During the post-intervention phase, females had larger relative risks of lung cancer mortality (1.33 versus 1.14; P.36), cardiovascular disease mortality (1.44 versus 0.93; P.03), and all-cause mortality (1.37 versus 0.98; P = .001) than males. Conclusions: The previously reported adverse effects of P-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant. Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females, and cardiovascular disease mortality primarily to females and to former smokers.