title: Involvement of DNA damage response pathways in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) has been known as one of the most lethal human malignancies, due to the difficulty of early detection, chemoresistance, and radioresistance, and is characterized by active angiogenesis and metastasis, which account for rapid recurrence and poor survival. Its development has been closely associated with multiple risk factors, including hepatitis B and C virus infection, alcohol consumption, obesity, and diet contamination. Genetic alterations and genomic instability, probably resulted from unrepaired DNA lesions, are increasingly recognized as a common feature of human HCC. Dysregulation of DNA damage repair and signaling to cell cycle checkpoints, known as the DNA damage response (DDR), is associated with a predisposition to cancer and affects responses to DNA-damaging anticancer therapy. It has been demonstrated that various HCC-associated risk factors are able to promote DNA damages, formation of DNA adducts, and chromosomal aberrations. Hence, alterations in the DDR pathways may accumulate these lesions to trigger hepatocarcinogenesis and also to facilitate advanced HCC progression. This review collects some of the most known information about the link between HCC-associated risk factors and DDR pathways in HCC. Hopefully, the review will remind the researchers and clinicians of further characterizing and validating the roles of these DDR pathways in HCC.
authors.affiliation: Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung City 801, Taiwan ; Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
authors.forename: Sheau-Fang
authors.initials: SF
authors.lastname: Yang
authors.affiliation: Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung City 831, Taiwan ; Cancer Center and Division of General & Gastroenterological Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan.
authors.forename: Chien-Wei
authors.identifier: 0000-0003-3177-2567
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung City 831, Taiwan ; Department of Pathology, Kaohsiung Armed Forces General Hospital, Kaohsiung City 802, Taiwan ; Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung City 804, Taiwan.
authors.forename: Ren-Jie
authors.initials: RJ
authors.lastname: Wei
authors.affiliation: Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung City 804, Taiwan.
authors.forename: Yow-Ling
authors.initials: YL
authors.lastname: Shiue
authors.affiliation: Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan ; Division of Hepato-Pancreatico-Biliary Surgery, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan.
authors.forename: Shen-Nien
authors.initials: SN
authors.lastname: Wang
authors.affiliation: Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung City 831, Taiwan.
authors.forename: Yao-Tsung
authors.identifier: 0000-0002-7780-7983
authors.initials: YT
authors.lastname: Yeh
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002869:Chromosome Aberrations; D018736:DNA Adducts / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics
chemical_list: D018736:DNA Adducts