Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, China.
Int J Gynecol Cancer. 2011 Nov;21(8):1407-13. doi: 10.1097/IGC.0b013e31823122c6.
8-Hydroxydeoxyguanosine (8-OHdG) is an oxidized nucleoside that can lead to misincorporation of bases. Human 8-oxoguanine DNA glycosylase (hOGG1) is the key defense enzyme against mutation by the cellular 8-OHdG in duplex DNA. The present study was aimed to explore whether the hOGG1 gene variants play an important role in the carcinogenesis of epithelial ovarian cancer (EOC).
Germ line variants in 5'-untranslated region (c.-18G>T, c.-23A>G, c.-45G>A, and c.-53G>C) and c.977C>G (Ser326Cys) polymorphism in exon7 of the hOGG1 gene in 420 sporadic EOCs and 840 controls were detected. Immunohistochemical and promoter luciferase activity assays were used to explore the effect of c.-18G>T variant on hOGG1 expression.
In contrast to type I EOC cases, patients with type II EOC were usually older, already in the advanced stage, and exhibited a common protein 53 (p53) overexpression. The frequencies of genotypes c.-18G/T and c.977G/G in hOGG1 were significantly high in the patients with type II EOC (odds ratio, 2.83; 95% confidence interval, 1.45-5.52; odds ratio, 1.66; 95% confidence interval, 1.26-2.17) but not in the patients with type I EOC. The average level of hOGG1 protein in the normal tissues adjacent to the type II EOC-carried c.-18G/T was lower than that with c.-18G/G (P = 0.01). The luciferase activity in the c.-18T allele was lower than that in the c.-18G allele (P = 0.001).
The genotypes of c.-18G/T in 5'-untranslated region and c.977G/G in exon7 of the hOGG1 gene would confer risk to type II EOC.
8-羟基脱氧鸟苷（8-OHdG）是一种氧化核苷，可导致碱基错误掺入。人 8-氧鸟嘌呤 DNA 糖基化酶（hOGG1）是细胞内 8-OHdG 在双链 DNA 中引起突变的关键防御酶。本研究旨在探讨 hOGG1 基因变异是否在卵巢上皮性癌（EOC）的发生中起重要作用。
在 420 例散发性 EOC 病例和 840 例对照中，检测 hOGG1 基因 5'-非翻译区（c.-18G>T、c.-23A>G、c.-45G>A 和 c.-53G>C）和外显子 7 中的 c.977C>G（Ser326Cys）多态性的种系变异。免疫组织化学和启动子荧光素酶活性测定用于研究 c.-18G>T 变异对 hOGG1 表达的影响。
与 I 型 EOC 病例相比，II 型 EOC 患者通常年龄较大，已处于晚期，并表现出常见的蛋白 53（p53）过度表达。在 II 型 EOC 患者中，hOGG1 的 c.-18G/T 和 c.977G/G 基因型的频率明显较高（比值比，2.83；95%置信区间，1.45-5.52；比值比，1.66；95%置信区间，1.26-2.17），但在 I 型 EOC 患者中则不然。与 c.-18G/G 相比，携带 c.-18G/T 的 II 型 EOC 附近正常组织中的 hOGG1 蛋白平均水平较低（P=0.01）。c.-18T 等位基因的荧光素酶活性低于 c.-18G 等位基因（P=0.001）。
hOGG1 基因 5'-非翻译区的 c.-18G/T 基因型和外显子 7 的 c.977G/G 基因型可能会增加 II 型 EOC 的发病风险。
