Elevated polycyclic aromatic hydrocarbon-DNA adducts in benign prostate and risk of prostate cancer in African Americans.
Elevated polycyclic aromatic hydrocarbon-DNA adducts in benign prostate and risk of prostate cancer in African Americans.
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DOI：
10.1093/carcin/bgs326
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发表时间：
2013
期刊：
影响因子：
4.7
通讯作者：
D. Tang;Oleksandr N. Kryvenko;Yun Wang;M. Jankowski;S. Trudeau;A. Rundle;B. Rybicki
中科院分区：
文献类型：
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作者：
D. Tang;Oleksandr N. Kryvenko;Yun Wang;M. Jankowski;S. Trudeau;A. Rundle;B. Rybicki
致癌物-DNA 加合物是 DNA 损伤的标志物，能够诱导癌基因和抑癌基因突变，从而导致癌变。我们之前已经表明，前列腺癌病例中的多环芳烃 (PAH)-DNA 加合物水平因细胞组织学而异，并且较高的加合物水平与生化复发相关。一项巢式病例对照研究在 6692 名具有组织病理学良性前列腺标本的男性历史队列中进行。通过免疫组织化学法测定 536 例前列腺癌病例对照对（59% 白人和 41% 非裔美国人）良性前列腺样本中的 PAH-DNA 加合物水平。我们估计了与较高加合物水平相关的后续前列腺癌的总体和种族分层风险。加合物水平升高（定义为高于对照组中位数）的男性患前列腺癌的风险略有增加[比值比 (OR) = 1.28，95% 置信区间 (CI) = 0.98-1.67，P = 0.07]。种族分层后，加合物水平升高与非裔美国男性的风险增加显着相关（OR = 1.56，CI = 1.00-2.44，*P = 0.05），但与白人男性无关（OR = 1.14，CI = 0.82-1.59，P = 0.45）。在入组后 1-4 年诊断的病例中，PAH-DNA 加合物水平升高与 60% 的前列腺癌风险增加显着相关（OR = 1.60，CI = 1.07-2.41），在随访的前 4 年内观察到非洲裔美国人的风险更大（OR = 4.71，CI = 1.97-11.26，***P = 0.0005）。按年龄或肿瘤等级分层的分析显示，风险没有额外的显着异质性。仅在非裔美国人中发现良性前列腺中高 PAH-DNA 加合物水平会增加前列腺癌风险；随访 4 年内风险最大，可能反映了组织学上尚未检测到的致癌过程。
Carcinogen-DNA adducts, a marker of DNA damage, are capable of inducing mutations in oncogenes and tumor suppressor genes, resulting in carcinogenesis. We have shown previously that polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels in prostate cancer cases vary by cellular histology and that higher adduct levels are associated with biochemical recurrence. A nested case-control study was conducted in a historical cohort of 6692 men with histopathologically benign prostate specimens. PAH-DNA adduct levels were determined by immunohistochemistry in benign prostate specimens from 536 prostate cancer case-control pairs (59% White and 41% African American). We estimated the overall and race-stratified risk of subsequent prostate cancer associated with higher adduct levels. Prostate cancer risk for men with elevated adduct levels (defined as greater than control group median) was slightly increased [odds ratio (OR) = 1.28, 95% confidence interval (CI) = 0.98-1.67, P = 0.07]. After race stratification, elevated adduct levels were significantly associated with increased risk in African American men (OR = 1.56, CI = 1.00-2.44, *P = 0.05) but not White men (OR = 1.14, CI = 0.82-1.59, P = 0.45). Elevated PAH-DNA adduct levels were significantly associated with 60% increased risk of prostate cancer among cases diagnosed 1-4 years after cohort entry (OR = 1.60, CI = 1.07-2.41) with a greater risk observed in African Americans within the first 4 years of follow-up (OR = 4.71, CI = 1.97-11.26, ***P = 0.0005). Analyses stratified by age or tumor grade revealed no additional significant heterogeneity in risk. Increased prostate cancer risk associated with high PAH-DNA adduct levels in benign prostate was found only in African Americans; risk was greatest within 4 years of follow-up, possibly reflecting a carcinogenic process not yet histologically detectable.