Department of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA.
Cancer Prev Res (Phila). 2011 Nov;4(11):1761-9. doi: 10.1158/1940-6207.CAPR-10-0343. Epub 2011 Sep 6.
The threat of prostate cancer and the significant and often negative impact of its treatment underscore the importance of prevention. High-grade prostatic intraepithelial neoplasia (HGPIN) has been identified as a potential premalignant lesion marking an increased risk of prostate cancer and substantial evidence suggests that men with HGPIN are in need of prostate cancer prevention. In vitro, in vivo, epidemiologic, and clinical trial evidence that selenium supplementation protects against prostate cancer motivated the study we report here: a double-blind, randomized, placebo-controlled trial of selenium 200 (μg/d) as selenomethionine in men with HGPIN. The primary endpoint was progression of HGPIN to prostate cancer over a 3-year period. This National Cancer Institute Intergroup trial was coordinated by the Southwest Oncology Group (SWOG). Of 619 enrolled patients, 423 randomized men with HGPIN (212 selenium and 211 placebo) were eligible (by central pathology review) and included in the primary analysis. Three-year cancer rates were 36.6% (placebo) versus 35.6% (selenium; P = 0.73, adjusted). The majority of patients who developed cancer on trial (70.8%, selenium and 75.5%, placebo) had a Gleason score of 6 or less than 6; there were no differences in Gleason scores between the two arms. Subset analyses included the finding of a nonsignificantly reduced prostate cancer risk (relative risk = 0.82; 95% CI: 0.40-1.69) in selenium versus placebo patients in the lowest quartile of baseline plasma selenium level (<106 ng/mL). Overall, and in all other subsets defined by baseline blood selenium levels, selenium supplementation had no effect on prostate cancer risk. The 36% prostate cancer rate in men with HGPIN indicates the association of this lesion with an elevated prostate cancer risk. Future study in this setting should focus on selenium-deficient populations and selenium pharmacogenetics.
前列腺癌的威胁以及其治疗的显著且常常是负面的影响突出了预防的重要性。高级别前列腺上皮内瘤变（HGPIN）已被确定为一种潜在的癌前病变，标志着前列腺癌风险增加，大量证据表明 HGPIN 男性需要进行前列腺癌预防。体外、体内、流行病学和临床试验证据表明，硒补充剂可预防前列腺癌，这激发了我们在此报告的研究：一项针对 HGPIN 男性的硒 200（μg/d）作为硒代蛋氨酸的双盲、随机、安慰剂对照试验。主要终点是在 3 年内 HGPIN 进展为前列腺癌。这项由美国国家癌症研究所（National Cancer Institute）组织的多中心临床试验由西南肿瘤协作组（Southwest Oncology Group，SWOG）协调。在 619 名入组患者中，有 423 名 HGPIN 随机男性（212 名硒组和 211 名安慰剂组）符合（经中心病理复查）并纳入主要分析。3 年癌症发生率为 36.6%（安慰剂）与 35.6%（硒；P = 0.73，调整后）。试验中发生癌症的大多数患者（硒组 70.8%，安慰剂组 75.5%）的 Gleason 评分为 6 或更低；两组之间的 Gleason 评分没有差异。亚组分析包括在基线血浆硒水平最低（<106ng/mL）的 quartile 中，与安慰剂相比，硒组前列腺癌风险显著降低（相对风险=0.82；95%置信区间：0.40-1.69）。总体而言，以及在根据基线血硒水平定义的所有其他亚组中，硒补充剂对前列腺癌风险没有影响。HGPIN 男性 36%的前列腺癌发生率表明该病变与前列腺癌风险增加相关。在这种情况下，未来的研究应集中在缺硒人群和硒药物遗传学上。
