OGG1、XRCC3 和 XRCC7 这些 DNA 修复基因是否会影响北印度人群患膀胱癌的易感性？

Do DNA repair genes OGG1, XRCC3 and XRCC7 have an impact on susceptibility to bladder cancer in the North Indian population?

机构信息

Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India.

出版信息

Mutat Res. 2009 Nov-Dec;680(1-2):56-63. doi: 10.1016/j.mrgentox.2009.09.008. Epub 2009 Oct 6.

DOI:10.1016/j.mrgentox.2009.09.008

PMID:19815090

Abstract

OBJECTIVE

Polymorphisms in DNA repair genes may be associated with altered DNA repair capacity, thereby influencing an individual's susceptibility to smoking-related cancers such as bladder cancer. Therefore, we sought to examine the correlation between single nucleotide polymorphisms in DNA repair genes and bladder cancer.

METHODOLOGY

We undertook a case-control study of 212 urothelial bladder cancer (UBC) cases and 250 controls to investigate the association between OGG1 (C1245G rs1052133), XRCC3 (C18067T, rs861539) and XRCC7 (G6721T, rs7003908) polymorphisms and bladder cancer susceptibility by PCR-RFLP and the ARMS method. We also investigated gene-environment interactions.

RESULTS

The OGG1 GG genotype was associated with an elevated risk of urothelial bladder cancer (UBC) (OR, 2.10; p, 0.028). XRCC7 + 6721 GG was also associated with increased susceptibility to UBC (OR, 4.45; p, 0.001). In a recessive model, the OGG1 GG genotype showed an increased risk of TaG(2,3) + T1G(1-3) tumors. Additionally, the OGG1 GG genotype in non-smokers represented a 2.46-fold greater risk (OR, 2.46; p, 0.035) in bladder cancer patients. Subsequent analysis demonstrated more pronounced association of XRCC7 with smokers (OR, 4.39; p, 0.001). XRCC7 also showed increased association with TaG(2,3) + T1G(1-3) tumors and muscle invasive tumors (OR, 3.16; p, 0.001 and OR, 4.24; p, 0.001, respectively). Multiple Cox regression analysis in non-muscle invasive bladder tumor (NMIBT) patients demonstrated an association of the OGG1 GG polymorphism with a high risk of recurrence in patients on cystoscopic surveillance (HR, 4.04; p, 0.013). Subsequently, shorter recurrence-free survival (log rank p, 0.024; CC/GG, 42/24) was observed.

CONCLUSION

Our data suggest association of a variant (GG) genotype of OGG1 with increased UBC susceptibility and a high risk of tumor recurrence in NMIBT patients on cystoscopic surveillance. XRCC7 G allele carriers (TG+GG) are also at an elevated risk for susceptibility to UBC as evidenced by a high odds ratio throughout the analysis.

摘要

目的

DNA 修复基因中的多态性可能与 DNA 修复能力的改变有关，从而影响个体对与吸烟相关的癌症（如膀胱癌）的易感性。因此，我们试图研究 DNA 修复基因中单核苷酸多态性与膀胱癌之间的相关性。

方法

我们进行了一项病例对照研究，共纳入 212 例尿路上皮膀胱癌（UBC）病例和 250 例对照，采用 PCR-RFLP 和 ARMS 法研究 OGG1（C1245G rs1052133）、XRCC3（C18067T、rs861539）和 XRCC7（G6721T、rs7003908）多态性与膀胱癌易感性的关系，并探讨了基因-环境相互作用。

结果

OGG1 GG 基因型与尿路上皮膀胱癌（UBC）的发病风险升高相关（OR，2.10；p，0.028）。XRCC7+6721 GG 基因型也与 UBC 的易感性增加相关（OR，4.45；p，0.001）。在隐性模型中，OGG1 GG 基因型的 TaG（2,3）+T1G（1-3）肿瘤风险增加。此外，非吸烟者中 OGG1 GG 基因型的膀胱癌患者患病风险增加 2.46 倍（OR，2.46；p，0.035）。进一步分析显示，XRCC7 与吸烟者的相关性更为显著（OR，4.39；p，0.001）。XRCC7 还与 TaG（2,3）+T1G（1-3）肿瘤和肌肉浸润性肿瘤的相关性增加（OR，3.16；p，0.001 和 OR，4.24；p，0.001）。非肌肉浸润性膀胱癌（NMIBT）患者的多变量 Cox 回归分析显示，OGG1 GG 多态性与膀胱镜监测患者的高复发风险相关（HR，4.04；p，0.013）。随后观察到无复发生存率较短（对数秩检验 p，0.024；CC/GG，42/24）。