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中国广西人群中 DNA 修复基因 XRCC7 多态性(rs#7003908 和 rs#10109984)与 AFB1 暴露相关的肝细胞癌。

DNA repair gene XRCC7 polymorphisms (rs#7003908 and rs#10109984) and hepatocellular carcinoma related to AFB1 exposure among Guangxi population, China.

机构信息

Department of Pathology Department of Medicine, Youjiang Medical College for Nationalities, Baise, Guangxi Zhuang Autonomous Region, China Department of Test Medicine, Southwest Hospital of Youjiang Medical College for Nationalities, Baise, Guangxi Zhuang Autonomous Region Department of Imaging Medicine (G2008) Department of Clinic Medicine (G2009), Youjiang Medical College for Nationalities, Baise, Guangxi Zhuang Autonomous Region, China.

出版信息

Hepatol Res. 2011 Nov;41(11):1085-93. doi: 10.1111/j.1872-034X.2011.00866.x. Epub 2011 Aug 26.

Abstract

AIM

The X-ray repair cross-complementing group 7 (XRCC7) plays an important role in the repair of DNA double-strand breaks by nonhomologous end-joining repair (NEJR) pathway. However, the role of XRCC7 polymorphisms (rs#7003908 and rs#10109984) possibly influencing NEJR capacity in hepatocellular carcinoma (HCC) induced by aflatoxin B1 (AFB1) has not been well elaborated.

METHODS

This hospital-based case-control study, including 348 patients with newly diagnosed HCC and 597 controls without any evidence of liver diseases, was conducted to elucidate the association between these two polymorphisms and the risk of HCC related to AFB1 exposure among a Guangxi population from a high AFB1-exposure area by means of TaqMAN-polymerase chain reaction technique.

RESULTS

We observed that HCC patients featured higher AFB1 exposure than control group (odds ratios [OR] = 6.49 and 6.75 for exposure years and exposure levels, respectively). Furthermore, these individuals with the genotypes of XRCC7 rs#7003908 G alleles (namely XRCC7-TG or -GG), compared the homozygote of XRCC7 rs#7003908 T alleles (XRCC7-TT), faced increasing risk of HCC (OR, 3.45 and 5.04; 95% confidence intervals [CIs], 2.40-4.94 and 3.28-7.76, respectively). We also found some evidence that this polymorphism interacted with AFB1-expousure years or levels in the process of HCC carcinogenesis. Additionally, XRCC7 rs#7003908 polymorphism was correlated with the levels of AFB1-DNA adducts (r = 0.142, P < 0.001). XRCC7 rs#10109984 polymorphism, however, did not modify the risk of HCC related to AFB1 exposure (P > 0.05).

CONCLUSION

These data suggest that XRCC7 rs#7003908 polymorphism may be one of the genetic modifiers for AFB1-related HCC among Guangxi population.

摘要

目的

X 射线修复交叉互补基因 7(XRCC7)在非同源末端连接修复(NHEJ)途径修复 DNA 双链断裂中发挥重要作用。然而,XRCC7 多态性(rs#7003908 和 rs#10109984)是否会影响黄曲霉毒素 B1(AFB1)诱导的肝癌(HCC)中的 NHEJ 能力尚未得到充分阐述。

方法

本病例对照研究以医院为基础,纳入 348 例新诊断 HCC 患者和 597 例无任何肝脏疾病证据的对照,采用 TaqMAN-聚合酶链反应技术,在广西一个来自高 AFB1 暴露地区的人群中,阐明这两种多态性与 AFB1 暴露相关 HCC 风险之间的关系。

结果

我们发现 HCC 患者的 AFB1 暴露水平高于对照组(暴露年限和暴露水平的比值比[OR]分别为 6.49 和 6.75)。此外,与 XRCC7 rs#7003908 T 等位基因纯合子(XRCC7-TT)相比,XRCC7 rs#7003908 G 等位基因(即 XRCC7-TG 或 -GG)的个体患 HCC 的风险增加(OR 分别为 3.45 和 5.04;95%置信区间[CI]分别为 2.40-4.94 和 3.28-7.76)。我们还发现一些证据表明,这种多态性在 HCC 癌变过程中与 AFB1 暴露年限或水平存在相互作用。此外,XRCC7 rs#7003908 多态性与 AFB1-DNA 加合物水平相关(r=0.142,P<0.001)。然而,XRCC7 rs#10109984 多态性并未改变 AFB1 暴露相关 HCC 的风险(P>0.05)。

结论

这些数据表明,XRCC7 rs#7003908 多态性可能是广西人群中 AFB1 相关 HCC 的遗传修饰因子之一。

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