Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India.
Mech Ageing Dev. 2012 Apr;133(4):127-32. doi: 10.1016/j.mad.2011.10.002. Epub 2011 Oct 12.
Carcinogens causes DNA damage, including oxidative lesions that are removed efficiently by the base excision repair (BER) pathway. Variations in BER genes may reduce DNA repair capacity, leading to development of urological cancers.
This study included 195 prostate cancer (PCa) and 212 bladder cancer (BC) patients and 250 controls who had been frequency matched by age, sex, and ethnicity. We genotyped XRCC1 Exon 6 (C>T), 9 (G>A), 10 (G>A), OGG1 Exon 7 (C>G) and APE1 Exon 5 (T>G) genes polymorphism using PCR-RFLP and ARMS.
GA of XRCC1 Exon 9 demonstrated increased risk with PCa as well as in BC (p=0.001; p=0.006). Similarly variant containing genotype revealed association with PCa (p=0.031). Haplotype of XRCC1 also associated with significant risk for PCa and BC. The APE1 GG genotype showed a decreased risk of BC (OR=0.25; p=0.017). Variant genotype GG of OGG1 demonstrated significant risk with BC (p=0.028).
Our observations suggested increased risk for PCa and BC in case of GA genotype for XRCC1, and variant GG in case of OGG1. However APE1 GG genotype conferred a protective association with BC susceptibility. Larger studies and the more SNPs in the same pathway are needed to verify these findings.
致癌物质会导致 DNA 损伤，包括可被碱基切除修复（BER）途径有效清除的氧化损伤。BER 基因的变异可能会降低 DNA 修复能力，从而导致泌尿系统癌症的发生。
本研究纳入了 195 例前列腺癌（PCa）患者、212 例膀胱癌（BC）患者和 250 例经年龄、性别和种族相匹配的对照者。我们采用 PCR-RFLP 和 ARMS 法对 XRCC1 外显子 6（C>T）、9（G>A）、10（G>A）、OGG1 外显子 7（C>G）和 APE1 外显子 5（T>G）基因多态性进行了基因分型。
XRCC1 外显子 9 的 GA 基因型与 PCa 以及 BC 均相关（p=0.001；p=0.006）。同样，含有变异型的基因型与 PCa 也存在关联（p=0.031）。XRCC1 的单体型也与 PCa 和 BC 的显著风险相关。APE1 的 GG 基因型显示出 BC 风险降低（OR=0.25；p=0.017）。OGG1 的变异型 GG 基因型与 BC 存在显著的风险相关（p=0.028）。
我们的观察结果表明，在 XRCC1 的 GA 基因型和 OGG1 的变异型 GG 基因型的情况下，PCa 和 BC 的风险增加。然而，APE1 的 GG 基因型与 BC 的易感性呈保护性相关。需要进行更大规模的研究，并对同一途径中的更多 SNP 进行验证，以证实这些发现。
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