Carcinogen DNA adducts and the risk of colon cancer: case-control study
Carcinogen DNA adducts and the risk of colon cancer: case-control study
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DOI：
10.1080/13547500701775449
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发表时间：
2008-03-01
期刊：
影响因子：
2.6
通讯作者：
Mohamed, G.
中科院分区：
文献类型：
--
作者：
Al-Saleh, I.;Arif, J.;Mohamed, G.
结直肠癌占费萨尔国王专科医院和研究中心所有肿瘤的8.5%。环境和饮食致癌物，如多环芳烃（PAHs）和杂环胺（HCAs）长期以来一直被怀疑在结肠癌病因学中发挥重要作用。我们设计了一项病例对照研究来检验DNA加合物的存在是否在结肠癌的病因学中发挥作用的假设。应用~（32）P-后标记技术对24例结肠癌和20例非癌组织进行了DNA加合物的测定。来自19名医院患者的正常组织作为对照。癌组织和非癌组织中每10（10）个核苷酸的加合物平均水平分别为151.75 +/- 217.27和114.81 +/- 186.10;然而，仅癌组织中的加合物显著高于对照（每10（10）个核苷酸32.78 +/- 57.51），p值为0.017。没有发现BPDE-DNA加合物。没有发现尿可替宁作为烟草烟雾的标志物和1-羟基芘作为个人的多环芳烃和DNA加合物的内部剂量的指标之间的关系。在逻辑回归模型中，只有癌组织中的加合物与随后的结肠癌风险相关，在校正年龄和在当前地区生活的持续时间后，比值比为3.587（95%置信区间0.833-15.448），但具有临界显著性（p = 0.086）。虽然很难从一个小的数据集得出一个明确的结论，但我们的初步结果表明DNA加合物在结肠癌发生过程中的潜在作用。需要更大样本量的额外研究来证实我们的初步发现。同样重要的是要确定这些未知的DNA加合物的结构特征，以便更好地了解环境致癌物是否在结肠癌的病因学中发挥作用。
Colorectal cancer represents 8.5% of all tumours at the King Faisal Specialist Hospital & Research Centre. Environmental and dietary carcinogens such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) have long been suspected to play a prominent role in colon cancer aetiology. We designed a case-control study to test the hypothesis of whether or not the presence of DNA adducts can play a role in the aetiology of colon cancer. DNA adducts were measured in 24 cancerous and 20 non-cancerous tissue samples of newly diagnosed colon cancer patients by 32 P-post-labelling technique. Normal tissue from 19 hospital patients served as controls. The mean levels of adducts per 10(10) nucleotides in cancerous and non-cancerous tissue were 151.75 +/- 217.27 and 114.81 +/- 186.10, respectively; however, only adducts in cancerous tissue were significantly higher than controls (32.78 +/- 57.51 per 10(10) nucleotides) with p-values of 0.017. No BPDE-DNA adducts were found. No relationship was found between urinary cotinine as a marker of tobacco smoke and 1-hydroxypyrene as an indicator of an individual's internal dose of PAHs and DNA adducts. In a logistic regression model, only adducts in cancerous tissue were associated with the subsequent risk of colon cancer, with an odds ratio of 3.587 (95% confidence interval 0.833-15.448) after adjustment for age and the duration of living in the current region, but of a borderline significance (p = 0.086). Although it is difficult to arrive at a definite conclusion from a small dataset, our preliminary results suggest the potential role of DNA adducts in the colon carcinogenesis process. Additional studies with larger sample sizes are needed to confirm our preliminary finding. It is also important to identify the structural characterization of these unknown DNA adducts in order to have a better understanding of whether or not environmental carcinogens play a role in the aetiology of colon cancer.