11.05.2022 | Research Letter
Association between genetic polymorphisms of base excision repair pathway and glioma susceptibility in Chinese children
verfasst von:
Yong-Ping Chen, Yu-Xiang Liao, Zhen-Jian Zhuo, Li Yuan, Hui-Ran Lin, Lei Miao, Xia Li, Xiao-Kai Huang, Jing-Ying Zhou, Jun Bian, Jing He
Erschienen in:
World Journal of Pediatrics
|
Ausgabe 9/2022
Einloggen, um Zugang zu erhalten
Excerpt
Glioma is an aggressive malignant primary tumor in the central nervous system [
1,
2]. Although the pathogenesis of glioma is unclear, the only identified environmental risk factor is ionizing radiation [
3]. However, other factors also may alter the glioma risk, among which gene polymorphisms may play prominent role in glioma susceptibility. Base excision repair (BER) is a DNA repair mechanism that maintains genome integrity and guarantees DNA base modification properly. Many significant and common proteins involved in the BER pathway are associated with cancer. They are poly (ADP-ribose) polymerase 1 (PARP1), human 8-oxo-guanine DNA glycosylase (hOGG1), flap endonuclease 1 (FEN1), apurinic/apyrimidinic endonuclease 1 (APEX1 or APE1), DNA ligase III (LIG3), and X-ray repair cross-complementing group 1 (XRCC1). PARP1 can regulate proteins by poly(ADP-ribosyl)ation and can repair damaged DNA by recruiting and modifying DNA repair complexes.
OGG1 gene is composed of six introns and seven exons, encoding HOGG1, which can initiate the BER pathway by hydrolyzing the glycosidic bond to produce abasic sites. FEN1 is a critical enzyme of the RAD2 structure-specific nuclease family that displays a variety of endonuclease and exonuclease activities and provides relevant biological functions. APEX1 is a multifunctional protein that has an essential role in cell proliferation, apoptosis, and differentiation as a transcription co-activator. LIG3 can participate in DNA double-strand broken repair due to strong binding activity, with the majority in the nucleus and the minority in mitochondria. XRCC1 interacts with LIG3 and PARP to form complexes, playing a substantial role in the BER pathway. DNA repair mechanisms have been expected to be promising and critical targets to treat glioma. The primary therapy for glioma is DNA alkylation but produces N7-methylguanine and N3-methyladenine, removal by BER [
4]. Given the importance of the BER pathway in DNA repair and that DNA repair is closely associated with glioma, the genetic variants in BER genes may confer glioma risk. However, the relationship between BER gene polymorphisms and glioma risk has not been fully understood. …