XPD 密码子 312 和 751 多态性、AFB1 暴露与肝细胞癌风险。
XPD codon 312 and 751 polymorphisms, and AFB1 exposure, and hepatocellular carcinoma risk.
机构信息
Department of Pathology, Youjiang Medical College for Nationalities, Baise, Guangxi Zhuang Autonomous Region, PR China.
出版信息
BMC Cancer. 2009 Nov 17;9:400. doi: 10.1186/1471-2407-9-400.
BACKGROUND
Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of hepatocellular carcinoma (HCC) related to the exposure of aflatoxin B1 (AFB1). In this study, we have focused on the polymorphisms of xeroderma pigmentosum complementation group D (XPD) codon 312 and 751 (namely Asp312Asn and Lys751Gln), involved in nucleotide excision repair.
METHODS
We conducted a case-control study including 618 HCC cases and 712 controls to evaluate the associations between these two polymorphisms and HCC risk for Guangxi population by means of TaqMan-PCR and PCR-RFLP analysis.
RESULTS
We found that individuals featuring the XPD genotypes with codon 751 Gln alleles (namely XPD-LG or XPD-GG) were related to an elevated risk of HCC compared to those with the homozygote of XPD codon 751 Lys alleles [namely XPD-LL, adjusted odds ratios (ORs) were 1.75 and 2.47; 95% confidence interval (CIs) were 1.30-2.37 and 1.62-3.76, respectively]. A gender-specific role was evident that showed an higher risk for women (adjusted OR was 8.58 for XPD-GG) than for men (adjusted OR = 2.90 for XPD-GG). Interestingly, the interactive effects of this polymorphism and AFB1-exposure information showed the codon 751 Gln alleles increase the risk of HCC for individuals facing longer exposure years (Pinteraction = 0.011, OR = 0.85). For example, long-exposure-years (> 48 years) individuals who carried XDP-GG had an adjusted OR of 470.25, whereas long-exposure-years people with XDP-LL were at lower risk (adjusted OR = 149.12). However, we did not find that XPD codon 312 polymorphism was significantly associated with HCC risk.
CONCLUSION
These findings suggest that XPD Lys751Gln polymorphism is an important modulator of AFB1 related-HCC development in Guangxi population.
背景
DNA 修复基因中的遗传多态性可能会影响个体 DNA 修复能力的个体差异，而这种差异可能与黄曲霉毒素 B1（AFB1）暴露相关的肝细胞癌（HCC）风险有关。在这项研究中，我们专注于核苷酸切除修复中涉及的 Xeroderma pigmentosum complementation group D（XPD）密码子 312 和 751 的多态性（即 Asp312Asn 和 Lys751Gln）。
方法
我们进行了一项病例对照研究，包括 618 例 HCC 病例和 712 例对照，通过 TaqMan-PCR 和 PCR-RFLP 分析评估这两种多态性与广西人群 HCC 风险之间的关系。
结果
我们发现，与 XPD 密码子 751 赖氨酸等位基因（即 XPD-LL）的纯合子相比，携带 XPD 密码子 751 谷氨酸等位基因（即 XPD-LG 或 XPD-GG）的个体患 HCC 的风险更高[分别为调整后的比值比（ORs）为 1.75 和 2.47；95%置信区间（CIs）分别为 1.30-2.37 和 1.62-3.76]。有明显的性别特异性作用，女性的风险更高（XPD-GG 的调整 OR 为 8.58），而男性的风险较低（XPD-GG 的调整 OR = 2.90）。有趣的是，该多态性与 AFB1 暴露信息的交互作用表明，密码子 751 谷氨酸等位基因增加了面临较长暴露年限的个体患 HCC 的风险（P 交互=0.011，OR=0.85）。例如，携带 XDP-GG 的长暴露年限（>48 年）个体的调整 OR 为 470.25，而长暴露年限（>48 年）的 XDP-LL 个体的风险较低（调整 OR=149.12）。然而，我们没有发现 XPD 密码子 312 多态性与 HCC 风险显著相关。
结论
这些发现表明，XPD Lys751Gln 多态性是广西人群 AFB1 相关 HCC 发生的重要调节因子。
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