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汉民族XRCC1基因399位密码子单核苷酸多态性与原发肝癌关系的研究

任翊 汪得胜 李卓 辛咏梅 殷继明 张斌 丁惠国 李宁

Journal of Hepatology|长期甲氨蝶呤治疗相关的肝纤维化风险可能被高估[J]. 临床肝胆病杂志, 2023, 39(2): 407-407. DOI: 10.3969/j.issn.1001-5256.2023.02.gwjpwzjj2.
引用本文: Journal of Hepatology|长期甲氨蝶呤治疗相关的肝纤维化风险可能被高估[J]. 临床肝胆病杂志, 2023, 39(2): 407-407. DOI: 10.3969/j.issn.1001-5256.2023.02.gwjpwzjj2.
Journal of Hepatology|Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated[J]. J Clin Hepatol, 2023, 39(2): 407-407. DOI: 10.3969/j.issn.1001-5256.2023.02.gwjpwzjj2.
Citation: Journal of Hepatology|Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated[J]. J Clin Hepatol, 2023, 39(2): 407-407. DOI: 10.3969/j.issn.1001-5256.2023.02.gwjpwzjj2.

汉民族XRCC1基因399位密码子单核苷酸多态性与原发肝癌关系的研究

详细信息
  • 中图分类号: R735.7

Study on the Relationship between Gene XRCC1 Codon 399 Single Nucleotide Polymorphisms and Primary Hepatic Carcinoma in Han Nationality

  • 摘要: 目的探讨汉民族XRCC1基因399位密码子单核苷酸多态性与原发肝癌之间的关系。方法原发肝癌患者50例,肝炎肝硬化患者61例,健康献血人员92例。针对XRCC1基因的10号外显子设计引物,PCR产物利用MspⅠ限制性酶切进行基因分型,基因型分成XRCC1 399Arg/Arg,399Arg/Gln,399Gln/Gln三种,分析XRCC1多态性与肝癌之间的关系。结果原发肝癌患者中XRCC1 399Arg/Arg 32例(64.0%),Arg/Gln 14例(28.0%),Gln/Gln 4例(8.0%);肝炎肝硬化患者中Arg/Arg 30例(49.2%),Arg/Gln 23例(37.7%),Gln/Gln 8例(13.1%);健康人群Arg/Arg 46例(50.0%),Arg/Gln 41例(44.5%),Gln/Gln 5例(5.5%)。以健康人群为对照组,XRCC1399Gln基因(基因型Arg/Gln和Gln/Gln)并不增加患肝癌的风险性(OR=0.563,95%CI:0.277-1.141,P=0.109);以肝炎肝硬化为对照组,XRCC1 399Gln基因同样与患肝癌的...

     

  • 据估计,长期暴露于甲氨蝶呤(MTX)导致严重肝纤维化的风险约为5%,这促使人们采取强化监测策略。然而,现有证据来源于回顾性研究,这些研究低估了肝病的风险因素。在Atallah等一项纵向队列研究中,使用两种非侵入性标志物评估了长期MTX治疗对肝纤维化的风险。

    在2014年—2021年,笔者从6个英国研究中心前瞻性招募了诊断为≥2年类风湿关节炎或银屑病的成年患者。MTX组包括接受MTX治疗≥6个月的患者,而未暴露组包括从未接受MTX的患者。所有的患者都进行了完整的肝脏分析,包括瞬时弹性成像(TE)和增强肝纤维化(ELF)标志物测量。

    共纳入999例患者,平均(60.8±12)岁,女性占62.3%。在976例有效TE值中,149例(15.3%)患者肝硬度≥7.9 kPa。在892例有效ELF值中,262例(29.4%)患者ELF≥9.8。年龄和BMI与肝硬度升高和肝纤维化独立相关。MTX累积剂量和持续时间都与肝硬度升高无关。糖尿病是与肝硬度≥7.9 kPa相关性最显著的危险因素(校正比值比=3.19,95%可信区间:1.95~5.20,P<0.001)。定期使用非甾体类抗炎药与ELF≥9.8的相关性最强(优势比=1.76,95%可信区间:1.20~2.56,P=0.003),表明类风湿性关节炎的关节炎症程度可能与作为肝纤维化的非侵入性标志物的ELF相混淆。

    笔者认为,先前可能高估了MTX本身导致的肝纤维化风险,有必要考虑修改MTX目前的监测准则。

    摘译自ATALLAH E, GROVE JI, CROOKS C, et al. Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated[J]. J Hepatol, 2023. DOI: 10.1016/j.jhep.2022.12.034. [Oline ahead of print]

    (吉林大学第一医院  肝胆胰内科  纪竹慧  辛桂杰  报道)

  • [1]Charames GS, Bapat B.Genomic instability and cancer[J].CurrMol Med, 2003, 3 (7) ∶589-596.
    [2]Ankathil R, Jyothish B, Madhavan J, et al.Deficient DNA repaircapacity:a predisposing factor and high risk predictive marker in fa-milial colorectal cancer[J].J Exp Clin Cancer Res, 1999, 18 (1) ∶33-37.
    [3]Goode EL, Ulrich CM, Potter JD.Polymorphisms in DNA repairgenes and associations with cancer risk[J].Cancer Epidemiol Bio-markers Prev, 2002, 11 (12) ∶1513-1530.
    [4] Moullan N, Cox DG, Ang埁le S, et al.Polymorphisms in the DNArepair gene XRCC1, breast cancer risk, and response toradiotherapy[J].Cancer Epidemiol Biomarkers Prev, 2003, 12 (11Pt1) ∶1168-1174.
    [5]Yeh CC, Sung FC, Rang R, et al.Polymorphisms of the XRCC1, XRCC3, &XPD genes, and colorectal cancer risk:a case-controlstudy in Taiwan[J].BMC Cancer, 2005, 28 (5) ∶12.
    [6]DianovaⅡ, Sleeth KM, Allinson SL, et al.XRCC1-DNA poly-merase beta interaction is required for efficient base excisionrepair[J].Nucleic Acids Res, 2004, 32 (8) ∶2550-2555.
    [7]Beernink PT, Hwang M, Ramirez M, et al.Specificity of protein in-teractions mediated by BRCTdomains of the XRCC1 DNArepair pro-tein[J].J Biol Chem, 2005, 280 (34) ∶30206-30213.
    [8]Caldecott KW.XRCC1 and DNA strand break repair[J].DNA Re-pair, 2003, 2 (9) ∶955-969.
    [9]Ladiges W, Wiley J, MacAuley A.Polymorphisms in the DNArepairgene XRCC1 and agerelated diseases[J].Mech Ageing Dev, 2003, 124 (1) ∶27-32.
    [10]Abdel-Rahman SZ, Soliman AS, Bondy ML, et al.Inheritance ofthe 194Trp and the 399Gln variant alleles of the DNA repair geneXRCC1 are associated with increased risk of early-onset colorectalcarcinoma in Egypt[J].Cancer Lett, 2000, 159 (1) ∶79-86.
    [11]Mort R, Mol L, McEwan C, et al.Lack of involvement of nucleo-tide excision repair gene polymorphisms in colorectal cancer[J].Br JCancer, 2003, 89 (2) ∶333-337.
    [12]Yu MW, Yang SY, Pan IJ, et al.Polymorphisms in XRCC1 andglutathione S-transferase genes and hepatitis B-related hepatocel-lular carcinoma[J].J Natl Cancer Inst, 2003, 95 (19) ∶1485-1488.
    [13]Long XD, Ma Y, Wei YP, et al.The polymorphisms of GSTM1, GSTT1, HYL1*2, and XRCC1, and aflatoxin B1-related hepato-cellular carcinoma in Guangxi population, China[J].Hepatol Res, 2006, 36 (1) ∶48-55.
    [14]Lee JM, Lee YC, Yang SY, et al.Genetic polymorphisms ofXRCC1 and risk of the esophageal cancer[J].Int J Cancer, 2001, 95 (4) ∶240-246.
    [15]Xing D, Qi J, Miao X, et al.Polymorphisms of DNA repair genesXRCC1 and XPD and their associations with risk of esophageal squa-mous cell carcinoma in a Chinese population[J].Int J Cancer, 2002, 100 (5) ∶600-605.
    [16]Hu Z, Ma H, Chen F, et al.XRCC1 polymorphisms and cancerrisk:a meta-analysis of 38 case-control studies[J].Cancer Epi-demiol Biomarkers Prev, 2005, 14 (7) ∶1810-1818.
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  • 出版日期:  2008-05-20
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