Abstract
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.
Highlights
Esophageal cancer exhibits a common malignancy with a poor prognosis, ranking the 10th most common cancers and taking a toll of ~400,000 deaths in 2012 worldwide [1], and esophageal squamous cell carcinoma (ESCC), accounting for ~90% esophageal cancer, is the predominant histological subtype throughout the world [2]
To clarify the role of chronic inflammation during the course of esophageal carcinogenesis, we examined a total of 109 endoscopic esophageal biopsies from nontumor individuals (Table 1)
The present work was designed to evaluate the association between chronic inflammation-related DNA damage and esophageal premalignant lesions
Summary
Esophageal cancer exhibits a common malignancy with a poor prognosis, ranking the 10th most common cancers and taking a toll of ~400,000 deaths in 2012 worldwide [1], and esophageal squamous cell carcinoma (ESCC), accounting for ~90% esophageal cancer, is the predominant histological subtype throughout the world [2]. The hugest burden of ESCC occurs in the “Asian esophageal cancer belt”, which extends from Caspian littoral of Iran, east to China, and north to Russia [3]. Our previous epidemiological study has shown an extremely high incidence of ESCC (74.47/100,000) in Nan’ao Island of Shantou, an isolated Chaoshan littoral region of southern China, from 1995 to 2004 [4], highlighting an urgent need for deeper understanding of its pathogenesis. The development of ESCC is associated with esophageal squamous dysplasia. Esophageal squamous dysplasia is regarded as the precursor lesion and risk factor for ESCC. A 13-year prospective follow-up study has demonstrated that patients with mild, moderate, or severe dysplasia have a risk of ESCC that is increased by a factor of 2.9, 9.8, or 28.3, respectively [5]. It is of great importance to explore the underlying mechanisms for the development of esophageal dysplasia
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