The Relationship Between Single-Nucleotide Polymorphisms, the Expression of DNA Damage Response Genes, and Hepatocellular Carcinoma in a Polish Population

被引:19
作者
Krupa, Renata [1 ]
Czarny, Piotr [2 ]
Wigner, Paulina [1 ]
Wozny, Joanna [3 ]
Jablkowski, Maciej [3 ]
Kordek, Radzislaw [4 ]
Szemraj, Janusz [2 ]
Sliwinski, Tomasz [1 ]
机构
[1] Univ Lodz, Dept Mol Genet, Lodz, Poland
[2] Med Univ Lodz, Dept Med Biochem, Mazowiecka 6-8, PL-92215 Lodz, Poland
[3] Med Univ Lodz, Dept Infect & Liver Dis, Lodz, Poland
[4] Med Univ Lodz, Dept Pathol, Lodz, Poland
关键词
DNA damage response; single-nucleotide polymorphism; mRNA expression; hepatitis C virus; hepatitis B virus; hepatocellular carcinoma; BASE EXCISION-REPAIR; POLY(ADP-RIBOSE) POLYMERASE PARP; BREAST-CANCER RISK; HEPATITIS-C VIRUS; OXIDATIVE-STRESS; LIGASE-III; LUNG-CANCER; UPDATED METAANALYSIS; ESOPHAGEAL CANCER; XRCC1;
D O I
10.1089/dna.2017.3664
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The molecular mechanism of hepatocellular carcinoma (HCC) is related to DNA damage caused by oxidative stress products induced by hepatitis B virus (HBV) or C (HCV) infection and exposure to environmental pollutants. Single-nucleotide polymorphisms (SNPs) of DNA damage response (DDR) genes may influence individual susceptibility to environmental risk factors and affect DNA repair efficacy, which, in turn, can influence the risk of HCC. The study evaluates a panel of 15 SNPs in 11 DDR genes (XRCC1, XRCC3, XPD, MUTYH, LIG1, LIG3, hOGG1, PARP1, NFIL1, FEN1, and APEX1) in 65 HCC patients, 50 HBV-and 50 HCVinfected non-cancerous patients, and 50 healthy controls. It also estimates the mRNA expression of nine DDR genes in cancerous and adjacent healthy liver tissues. Two of the investigated polymorphisms (rs1052133 and rs13181) were associated with HCC risk. For all investigated genes, the level of mRNA was significantly lower in HCC cancer tissue than in non-cancerous liver tissue. Seven of the investigated polymorphisms were statistically related to gene expression in cancer tissues. The disruption of DDR genes may be responsible for hepatocellular transformation in HCV-infected patients.
引用
收藏
页码:693 / 708
页数:16
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