Abstract
Gastric cardia cancer (GCC) is a highly aggressive disease associated with chronic inflammation. To investigate the relationship between DNA damage response (DDR) and chronic inflammation, we collected 100 non-tumor gastric cardia specimens of Chaoshan littoral, a high-risk region for esophageal and gastric cardia cancer. A significantly higher proportion of severe chronic inflammation was found in dysplastic epithelia (80.9%) in comparison with that in non-dysplastic tissues (40.7%) (P<0.001). Immunohistochemical analysis demonstrated that DNA damage response was parallel with the chronic inflammation degrees from normal to severe inflammation (P<0.05). We found that DNA damage response was progressively increased with the progression of precancerous lesions (P<0.05). These findings provide pathological evidence that persistent chronic inflammation-related DNA damage response may be a driving force of gastric cardia carcinogenesis. Based on these findings, DNA damage response in non-malignant tissues may become a promising biomedical marker for predicting malignant transformation in the gastric cardia.
Highlights
Gastric cancer represents the fourth most common cancer and second leading cause of cancer-related death worldwide, taking a toll of approximately 738,000 people in 2008 alone [1]
Our results revealed that severe chronic inflammation was more frequently observed in dysplastic tissues (80.9%), such as low-grade intraepithelial neoplasia (LGIN) and highgrade intraepithelial neoplasia (HGIN) in comparison with that in non-dysplastic tissues (40.7%) (P
We observed that dysplastic epithelial cells of the gastric cardia were frequently accompanied by severe chronic inflammation characterized by macrophage and lymphocyte infiltration, prompting us to seek the underlying mechanisms bridging the gap between chronic inflammation and gastric cardia carcinogenesis
Summary
Gastric cancer represents the fourth most common cancer and second leading cause of cancer-related death worldwide, taking a toll of approximately 738,000 people in 2008 alone [1]. It was once considered as a single entity. The vast majority of cancers originating from gastric cardia are adenocarcinomas based on histopathological features These epidemiological and histopathological characteristics confer uniqueness to GCC as a clinical entity. The gastro-esophageal junction (including the proximal gastric cardia region) is an anatomical location with a remarkably high and rapidly rising incidence of adenocarcinoma [4,5,6], while the underlying mechanisms for the development of GCC are poorly understood [7]
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