Chronic inflammation-related DNA damage response: a driving force of gastric cardia carcinogenesis
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Runhua Lin1,2,*, Dejun Xiao1,4,*, Yi Guo3, Dongping Tian1,2, Hailong Yun1,2, Donglin Chen1,2 and Min Su1,2
1 Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, PR China
2 The Judicial Critical Center, Shantou University Medical College, Shantou, Guangdong, PR China
3 Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, PR China
4 Clinical Laboratory of Ganzhou People’s Hospital, Ganzhou, Jiangxi, PR China
* These authors contributed equally to this work
Min Su, email:
Keywords: chronic inflammation, DNA damage response, precancerous lesions, genomic instability, gastric cardia carcinogenesis
Received: November 10, 2014 Accepted: December 25, 2014 Published: December 30, 2014
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.
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