Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2958-68. doi: 10.1158/1055-9965.EPI-10-0364. Epub 2010 Sep 17.
Evidence for an association between selenium status and prostate cancer risk is still inconclusive. Anticarcinogenic effects of selenium are supposedly mediated through cellular protective and redox properties of selenoenzymes in vivo. We evaluated the association between serum selenium status and prostate cancer risk in a population with relative low selenium concentrations considering effect modification by genetic variants in selenoprotein genes.
A case-control study of 248 incident prostate cancer cases and 492 matched controls was nested within the EPIC-Heidelberg cohort. Baseline blood samples were analyzed for serum selenium and selenoprotein P concentrations and glutathione peroxidase activity. Genotyping was carried out for SEP15 (rs5859, rs540049), SEPP1 (rs3877899, rs7579), GPX1 (rs1050450), and GPX4 (rs713041). Conditional logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI).
The OR for prostate cancer was 0.89 (95% CI, 0.79-1.01) per 10 μg/L increase of serum selenium concentration. This association was modified by rs1050450 (C>T) in GPX1 (P(interaction) = 0.03), with carriers of one or two T alleles having a significantly reduced OR of 0.87 (95% CI, 0.76-0.99). Furthermore, there was an association between rs7579 genotype in SEPP1 and prostate cancer risk (OR, 1.72; 95% CI, 0.99-2.98).
Our results support a role of selenium and polymorphisms in selenoenzymes in prostate cancer etiology, which warrants confirmation in future studies.
These findings might help to explain biological effects of selenium in prostate cancer development in order to overcome inconsistencies arising from former studies.
关于硒状态与前列腺癌风险之间的关联，目前尚无定论。硒的抗癌作用据推测是通过体内硒酶的细胞保护和氧化还原特性介导的。我们评估了在硒浓度相对较低的人群中，考虑到硒蛋白基因遗传变异的作用修饰，血清硒状态与前列腺癌风险之间的关联。
这项病例对照研究包括 248 例新发前列腺癌病例和 492 例匹配对照，嵌套在 EPIC-Heidelberg 队列中。基线血样用于分析血清硒和硒蛋白 P 浓度以及谷胱甘肽过氧化物酶活性。对 SEP15（rs5859、rs540049）、SEPP1（rs3877899、rs7579）、GPX1（rs1050450）和 GPX4（rs713041）进行基因分型。使用条件逻辑回归计算调整后的比值比（OR）和 95%置信区间（95%CI）。
血清硒浓度每增加 10μg/L，前列腺癌的 OR 为 0.89（95%CI，0.79-1.01）。这种关联受到 GPX1 中 rs1050450（C>T）的修饰（P(交互) = 0.03），携带一个或两个 T 等位基因的个体的 OR 显著降低至 0.87（95%CI，0.76-0.99）。此外，SEPP1 中的 rs7579 基因型与前列腺癌风险之间存在关联（OR，1.72；95%CI，0.99-2.98）。
我们的结果支持硒和硒酶的多态性在前列腺癌病因学中的作用，这需要在未来的研究中得到证实。
这些发现可能有助于解释硒在前列腺癌发展中的生物学作用，以克服以前研究中出现的不一致性。
