title: Chronic inflammation-associated genomic instability paves the way for human esophageal carcinogenesis.
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.
authors.affiliation: Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515031, PR China.
authors.forename: Runhua
authors.initials: R
authors.lastname: Lin
authors.affiliation: Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515031, PR China.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515031, PR China.
authors.forename: Jiaxuan
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515031, PR China.
authors.forename: Dongping
authors.initials: D
authors.lastname: Tian
authors.affiliation: Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515031, PR China.
authors.forename: Zhijin
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515031, PR China.
authors.forename: Donglin
authors.initials: D
authors.lastname: Chen
authors.affiliation: Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515031, PR China.
authors.forename: Zexin
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Institute of Clinical Pathology, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515031, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Su
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D042822:Genomic Instability; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged
chemical_list: C468783:H2AX protein, human; D006657:Histones; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
keywords: DNA double-strand breaks; chronic inflammation; esophageal carcinogenesis; genomic instability; oxidative DNA damage