Chronic inflammation-associated genomic instability paves the way for human esophageal carcinogenesis.
Chronic inflammation-associated genomic instability paves the way for human esophageal carcinogenesis.
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DOI：
10.18632/oncotarget.8356
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发表时间：
2016-04-26
期刊：
影响因子：
--
通讯作者：
Su M
中科院分区：
文献类型：
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作者：
Lin R;Zhang C;Zheng J;Tian D;Lei Z;Chen D;Xu Z;Su M
慢性炎症与癌症发展的风险增加有关，而慢性炎症与食管癌发生之间的联系迄今仍不清楚。本研究旨在探讨慢性炎症与DNA损伤的关系，以及DNA损伤在食管癌发生过程中的可能作用。对来自潮汕沿岸的109例食管鳞状细胞癌（ESCC）患者的内镜下食管活检组织进行了检查，以评估慢性炎症与组织学严重程度之间的关系，并收集了204例ESCC患者的食管非肿瘤样本。免疫组化检测DNA氧化损伤和DNA双链断裂。慢性炎症程度与食管癌前病变呈显著正相关（rs = 0.37，P < 0.01）。免疫组化分析显示，DNA氧化损伤水平与慢性炎症程度呈正相关（rs = 0.21，P < 0.05）。DNA氧化损伤程度与组织学严重程度呈正相关（rs = 0.49，P < 0.01）。发现DSB的范围随炎症程度和癌前病变的进展而进行性增加（P < 0.001）。总的来说，这些研究结果提供了证据，慢性炎症相关的基因组不稳定性与食管癌的发生，并建议食管癌的早期检测和干预的可能性。
Chronic inflammation is associated with increased risk of cancer development, whereas the link between chronic inflammation and esophageal carcinogenesis is still obscure heretofore. This study aimed to investigate the relationship between chronic inflammation and DNA damage, as well as the possible role of DNA damage in esophageal carcinogenic process. Endoscopic esophageal biopsies from 109 individuals from Chaoshan littoral, a high-risk region for esophageal squamous cell carcinoma (ESCC), were examined to evaluate the association between chronic inflammation and histological severity, while additional 204 esophageal non-tumor samples from patients with ESCC were collected. Immunohistochemistry was performed to detect the oxidative DNA damage and DNA double-strand breaks (DSBs). Significantly positive correlation was observed between degree of chronic inflammation and esophageal precursor lesions (rs = 0.37, P < 0.01). Immunohistochemical analysis showed that oxidative DNA damage level was positively correlated with the degree of chronic inflammation (rs = 0.21, P < 0.05). Moreover, the level of oxidative DNA damage positively correlated with histological severity (rs = 0.49, P < 0.01). We found that the extent of DSBs was progressively increased with inflammation degree (P < 0.01) and the progression of precancerous lesions (P < 0.001). Collectively, these findings provide evidence linking chronic inflammation-associated genomic instability with esophageal carcinogenesis and suggest possibilities for early detection and intervention of esophageal carcinogenesis.