Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).
Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).
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DOI：
10.1001/jama.2008.864
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发表时间：
2009-01-07
影响因子：
120.7
通讯作者：
Coltman, Charles A., Jr.
中科院分区：
文献类型：
--
作者：
Lippman, Scott M.;Klein, Eric A.;Goodman, Phyllis J.;Lucia, M. Scott;Thompson, Ian M.;Ford, Leslie G.;Parnes, Howard L.;Minasian, Lori M.;Gaziano, J. Michael;Hartline, Jo Ann;Parsons, J. Kellogg;Bearden, James D., III;Crawford, E. David;Goodman, Gary E.;Claudio, Jaime;Winquist, Eric;Cook, Elise D.;Karp, Daniel D.;Walther, Philip;Lieber, Michael M.;Kristal, Alan R.;Darke, Amy K.;Arnold, Kathryn B.;Ganz, Patricia A.;Santella, Regina M.;Albanes, Demetrius;Taylor, Philip R.;Probstfield, Jeffrey L.;Jagpal, T. J.;Crowley, John J.;Meyskens, Frank L., Jr.;Baker, Laurence H.;Coltman, Charles A., Jr.
对两个随机对照试验(RCT)以及支持性流行病学和临床前的二次分析表明，硒和维生素E在预防前列腺癌方面具有潜力。确定在相对健康的男性中，硒或维生素E或两者都可以预防前列腺癌，毒性很小或没有毒性。计划中的32,400名男性以双盲方式随机服用硒、维生素E、硒加维生素E和安慰剂。参与者被招募并在美国、加拿大和波多黎各的社区实践、当地医院和医疗保健组织以及三级癌症中心进行跟踪。基线资格包括50岁或50岁以上(非裔美国人)或55岁或55岁以上(所有其他人)，血清前列腺特异性抗原(PSA)≤4 ng/mL，以及直肠指检(DRE)不怀疑前列腺癌。在2001至2004年间，35,533名男性(由于应计比率快于预期，比计划多10%)被随机分配到四个研究小组，这四个小组在所有潜在的重要风险因素方面都得到了很好的平衡。口服硒(L-硒蛋氨酸200微克/天)和匹配的维生素E安慰剂、维生素E(400IU/天的所有RAC-α-生育酚醋酸酯)和匹配的硒安慰剂，或两者结合或安慰剂+安慰剂，计划至少7年至最长12年。前列腺癌(由常规社区诊断标准确定)和预先指定的次要结果，包括肺癌、结直肠癌和全身癌症。在数据和安全监测委员会的建议下，研究补充剂在计划的7年中期分析中被停止，因为证据令人信服地表明，任何一种研究试剂(P<；0.0001)都没有好处，也没有可能对计划的程度有好处，并进行了额外的随访。截至2008年10月23日，总体随访的中位数为5.46年(范围为4.17至7.33)。与安慰剂(n=416)相比，前列腺癌的风险比(前列腺癌数量，99%可信区间[CI])：维生素E(n=473；CI，0.91-1.41)为1.13，硒(n=432，CI，0.83-1.30)为1.04，联合用药(n=437，CI，0.83-1.31)为1.05。在任何预先指定的癌症终点中，没有显著差异(所有p值均为0.15)。服用维生素E组患前列腺癌(P=0.06；相对危险度[RR]=1.13；99%CI，0195-1.35)和服用硒组患2型糖尿病(P=0.16；RR=1.07；99%CI，0.94-1.22)无显著增加，但联合用药组未观察到。在所使用的剂量和配方中，单独或联合使用硒或维生素E并不能预防前列腺癌。
Secondary analyses of two randomized controlled trials (RCTs) and supportive epidemiologic and preclinical indicated the potential of selenium and vitamin E for preventing prostate cancer. To determine whether selenium or vitamin E or both could prevent prostate cancer with little or no toxicity in relatively healthy men. Randomization of a planned 32,400 men to selenium, vitamin E, selenium plus vitamin E, and placebo in a double-blinded fashion. Participants were recruited and followed in community practices, local hospitals and HMOs, and tertiary cancer centers in the United States, Canada and Puerto Rico. Baseline eligibility included 50 years or older (African American) or 55 years or older (all others), a serum prostate-specific antigen (PSA) ≤ 4 ng/mL, and a digital rectal examination (DRE) not suspicious for prostate cancer. Between 2001 and 2004, 35,533 men (10% more than planned because of a faster-than-expected accrual rate) were randomly assigned to the four study arms, which were well balanced with respect to all potentially important risk factors. Oral selenium (200 µg/day from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/day of all rac-α-tocopheryl acetate) and matched selenium placebo, or the two combined or placebo plus placebo for a planned minimum of 7 and maximum of 12 years. Prostate cancer (as determined by routine community diagnostic standards) and prespecified secondary outcomes including lung, colorectal and overall cancer. Study supplements were discontinued at the recommendation of the Data and Safety Monitoring Committee at a planned 7-year interim analysis because the evidence convincingly demonstrated no benefit from either study agent (p < 0.0001) and no possibility of a benefit to the planned degree with additional follow-up. As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17 and 7.33). Hazard ratios (number of prostate cancers, 99% confidence intervals [CIs]) for prostate cancer were 1.13 for vitamin E (n=473; CI, 0.91–1.41), 1.04 for selenium (n=432; CI, 0.83–1.30), and 1.05 for the combination (n=437; CI, 0.83–1.31) compared with placebo (n=416). There were no significant differences (all p-values > 0.15) in any prespecified cancer endpoints. There were nonsignificant increased risks of prostate cancer in the vitamin E arm (p=0.06; relative risk [RR]=1.13; 99% CI, 0l95–1.35) and of Type 2 diabetes mellitus in the selenium arm (p=0.16; RR=1.07; 99% CI, 0.94–1.22), but they were not observed in the combination arm. Selenium or vitamin E, alone or in combination, did not prevent prostate cancer in this population at the doses and formulations used.
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影响因子：
10.3
作者：
Kirsh, VA;Hayes, RB;Peters, U
通讯作者：
Peters, U
影响因子：
158.5
作者：
Bertagnolli, Monica M.;Eagle, Craig J.;Hawk, Ernest T.
通讯作者：
Hawk, Ernest T.
影响因子：
6.2
作者：
Hoffman, RM;Gilliland, FD;Potosky, AL
通讯作者：
Potosky, AL
影响因子：
6.6
作者：
Harlan, SR;Cooperberg, MR;Carroll, PR
通讯作者：
Carroll, PR
影响因子：
3.3
作者：
Meyskens, Frank L., Jr.;McLaren, Christine E.;Gerner, Eugene W.
通讯作者：
Gerner, Eugene W.