Graff Rebecca E, Judson Gregory, Ahearn Thomas U, Fiorentino Michelangelo, Loda Massimo, Giovannucci Edward L, Mucci Lorelei A, Pettersson Andreas
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
Prostate. 2017 May;77(6):647-653. doi: 10.1002/pros.23312. Epub 2017 Jan 19.
Few studies have considered etiological differences across molecular subtypes of prostate cancer, despite potential to improve opportunities for precision prevention of a disease for which modifiable risk factors have remained elusive. Factors that lead to DNA double-strand breaks, such as oxidative stress, may promote the formation of the TMPRSS2:ERG gene fusion in prostate cancer. We tested the hypothesis that increasing levels of pre-diagnostic circulating antioxidants, which may reduce oxidative stress, are associated with lower risk of developing TMPRSS2:ERG positive prostate cancer.
We conducted a nested case-control study, including 370 cases and 2,470 controls, to evaluate associations between pre-diagnostic α- and β-carotene, α- and γ-tocopherol, β-cryptoxanthin, lutein, lycopene, retinol, and selenium with the risk of prostate cancer by ERG protein expression status (a marker of TMPRSS2:ERG). Multivariable unconditional polytomous logistic regression was used to calculate odds ratios and 95% confidence intervals.
We did not find any of the antioxidants to be significantly associated with the risk of prostate cancer according to ERG status.
The results do not support the hypothesis that circulating pre-diagnostic antioxidant levels protect against developing TMPRSS2:ERG positive prostate cancer. Additional studies are needed to explore mechanisms for the development of TMPRSS2:ERG positive disease. Prostate 77: 647-653, 2017. © 2017 Wiley Periodicals, Inc.
尽管有可能改善前列腺癌精准预防的机会，但很少有研究考虑前列腺癌分子亚型的病因差异，而前列腺癌的可改变风险因素一直难以捉摸。导致DNA双链断裂的因素，如氧化应激，可能促进前列腺癌中TMPRSS2:ERG基因融合的形成。我们检验了这样一个假设，即增加诊断前循环抗氧化剂水平（这可能降低氧化应激）与降低发生TMPRSS2:ERG阳性前列腺癌的风险相关。
我们进行了一项巢式病例对照研究，包括370例病例和2470例对照，以评估诊断前α-和β-胡萝卜素、α-和γ-生育酚、β-隐黄质、叶黄素、番茄红素、视黄醇和硒与ERG蛋白表达状态（TMPRSS2:ERG的标志物）相关的前列腺癌风险之间的关联。采用多变量无条件多分类逻辑回归计算比值比和95%置信区间。
根据ERG状态，我们未发现任何一种抗氧化剂与前列腺癌风险有显著关联。
结果不支持以下假设，即诊断前循环抗氧化剂水平可预防TMPRSS2:ERG阳性前列腺癌的发生。需要进一步研究来探索TMPRSS2:ERG阳性疾病的发病机制。《前列腺》77: 647 - 653, 2017。© 2017威利期刊公司。
