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OGG1基因Ser326Cys多态性与肺癌腺癌之间存在有限关联。

A limited association of OGG1 Ser326Cys polymorphism for adenocarcinoma of the lung.

作者信息

Ito Hidemi, Hamajima Nobuyuki, Takezaki Toshiro, Matsuo Keitaro, Tajima Kazuo, Hatooka Shunzo, Mitsudomi Tetsuya, Suyama Motokazu, Sato Shigeki, Ueda Ryuzo

机构信息

Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.

出版信息

J Epidemiol. 2002 May;12(3):258-65. doi: 10.2188/jea.12.258.

Abstract

The 8-oxoguanine DNA glycosylase (OGG1) repairs DNA by removing 8-hydroxyguanine, a highly mutagenic oxidative DNA adduct. Recently, the gene for OGG1 was cloned and several polymorphisms have been reported. Because environmental carcinogens produce 8-hydroxyguanine residues that potentially cause oncogenic mutations by mismatching to this modified base, the capacity to repair these lesions can be involved in cancer susceptibility. This study investigated the association between OGG1 Ser326Cys polymorphism and risk of the lung adenocarcinoma for Japanese by a prevalent case-control study in Japan. The subjects comprised 138 cases and 241 non-cancer outpatients as controls. OGG1 gene polymorphism was genotyped by a PCR-CTPP (polymerase chain reaction with confronting two-pair primers) method. The distribution of OGG1 Ser326Cys genotype among controls (Ser/Ser, 28.3%; Ser/Cys, 49.2%; and Cys/Cys, 22.5%) was not different from that among cases (Ser/Ser, 29.0%; Ser/Cys, 51.4%; and Cys/Cys, 24.0%). The sex-age adjusted odds ratio (OR) was 1.06 with 95% confidence interval (CI) 0.64-1.76 for Ser/Cys genotype and 0.81 with 0.44-1.52 for Cys/Cys genotype. The ORs according to the interval between diagnosis and study enrollment were also examined because the polymorphism was a potential prognostic factor of lung cancer. The ORs of Ser/Cys and Cys/Cys genotypes in the cases less than 3 years after diagnosis were higher than overall ORs; 1.86 (95%CI, 0.91-3.77), and 1.46 (0.64-3.35), respectively. The OR for smoking was not statistically different among genotype, though the sample size was too small to detect even a moderate interaction. This study supported the first study by Sugimura et al (Cancer Epidemiol Biomarkers Prev, 1999; 8: 669-674), that the association of OGG1 Ser326Cys polymorphism was limited for the risk of lung adenocarcinoma.

摘要

8-氧代鸟嘌呤DNA糖基化酶(OGG1)通过去除8-羟基鸟嘌呤来修复DNA,8-羟基鸟嘌呤是一种具有高度诱变作用的氧化性DNA加合物。最近,OGG1基因被克隆出来,并且已经报道了几种多态性。由于环境致癌物会产生8-羟基鸟嘌呤残基,这些残基可能通过与这种修饰碱基错配而导致致癌突变,因此修复这些损伤的能力可能与癌症易感性有关。本研究通过在日本进行的一项现患病例对照研究,调查了日本人群中OGG1基因Ser326Cys多态性与肺腺癌风险之间的关联。研究对象包括138例病例和241名非癌症门诊患者作为对照。采用聚合酶链反应-对抗双引物法(PCR-CTPP)对OGG1基因多态性进行基因分型。对照组中OGG1基因Ser326Cys基因型的分布(Ser/Ser,28.3%;Ser/Cys,49.2%;Cys/Cys,22.5%)与病例组(Ser/Ser,29.0%;Ser/Cys,51.4%;Cys/Cys,24.0%)没有差异。调整性别和年龄后的优势比(OR),Ser/Cys基因型为1.06,95%置信区间(CI)为0.64 - 1.76;Cys/Cys基因型为0.81,95%CI为0.44 - 1.52。由于该多态性是肺癌的一个潜在预后因素,因此还根据诊断与研究入组之间的时间间隔对OR进行了检查。诊断后不到3年的病例中,Ser/Cys和Cys/Cys基因型的OR高于总体OR;分别为1.86(95%CI,0.91 - 3.77)和1.46(0.64 - 3.35)。尽管样本量过小,甚至无法检测到中等程度的相互作用,但不同基因型之间吸烟的OR在统计学上没有差异。本研究支持了Sugimura等人的第一项研究(《癌症流行病学、生物标志物与预防》,1999年;8:669 - 674),即OGG1基因Ser326Cys多态性与肺腺癌风险的关联有限。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95fa/10499484/2583554346f7/je-12-258-g001.jpg

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