Krupa Renata, Czarny Piotr, Wigner Paulina, Wozny Joanna, Jablkowski Maciej, Kordek Radzislaw, Szemraj Janusz, Sliwinski Tomasz
1 Department of Molecular Genetics, University of Lodz , Lodz, Poland .
2 Department of Medical Biochemistry, Medical University of Lodz , Lodz, Poland .
DNA Cell Biol. 2017 Aug;36(8):693-708. doi: 10.1089/dna.2017.3664. Epub 2017 Jun 9.
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 HCV-infected 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.
肝细胞癌（HCC）的分子机制与乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）感染以及暴露于环境污染物所诱导的氧化应激产物导致的DNA损伤有关。DNA损伤反应（DDR）基因的单核苷酸多态性（SNP）可能影响个体对环境风险因素的易感性，并影响DNA修复效率，进而可能影响HCC的风险。该研究评估了65例HCC患者、50例HBV感染的非癌患者、50例HCV感染的非癌患者以及50例健康对照中11个DDR基因（XRCC1、XRCC3、XPD、MUTYH、LIG1、LIG3、hOGG1、PARP1、NFIL1、FEN1和APEX1）中的15个SNP。该研究还估计了9个DDR基因在癌性和相邻健康肝组织中的mRNA表达。所研究的两个多态性（rs1052133和rs13181）与HCC风险相关。对于所有研究的基因，HCC癌组织中的mRNA水平显著低于非癌肝组织。所研究的7个多态性与癌组织中的基因表达在统计学上相关。DDR基因的破坏可能是HCV感染患者肝细胞转化的原因。
