Martin Robert C G, Lan Qing, Hughes Kalista, Doll Mark A, Martini Benjamin D, Lissowska Jolanta, Zatonski Witold, Rothman Nathaniel, Hein David W
Department of Surgery, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.
J Surg Res. 2005 Mar;124(1):92-7. doi: 10.1016/j.jss.2004.09.009.
Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species, constituting a major cellular defense mechanism against agents that induce oxidative stress. A genetic polymorphism in the mitochondrial targeting sequence of this gene has been associated with increased cancer risk. This one base pair transition (-9 T>C) leads to a Val to Ala amino acid change in the mitochondrial targeting sequence. In addition, the MnSOD promoter contains an activator protein-2 (AP-2) binding site that modifies transcription of MnSOD. Mutations have been identified in the proximal region of the promoter in human tumor cell lines. One of these mutations (-102 C>T) has been shown to change the binding pattern of AP-2, leading to a reduction in transcriptional activity. The aim of our study was to investigate possible associations of the (-9 T>C) and (-102 C>T) polymorphisms with gastric cancer in a population-based case-control study conducted in Warsaw, Poland.
DNA was obtained from a population based case-control study of stomach cancer conducted in Warsaw, Poland, between 1994 and 1996. The MnSOD -9 T>C genotype was determined by PCR-RFLP assay. The MnSOD -102 C>T genotype was determined using a TaqMan allele discrimination assay.
The frequency of the -102 C>T polymorphism was 41% (38/91) in gastric cancer cases and 38% (50/130) in the controls (odds ratio [OR] 1.1, 95% confidence interval [CI] 0.6-2.1). The frequency of the -9 T>C polymorphism was 44% (202/464) in cases and 56% (262/464) in controls (OR 1.1; 95% CI 0.9-1.37). The lack of association was observed in both non-smokers (OR 1.5; 95% CI 0.7-2.34) and smokers (OR 1.1; 95% CI 0.7-1.7). Furthermore, the association was not significant when smokers were segregated by extent of smoking history.
The association of the manganese superoxide dismutase polymorphisms at -102 C>T and the -9 T>C were not found to be associated with gastric cancer in a Polish case-control study.
锰超氧化物歧化酶（MnSOD）在清除线粒体活性氧中起关键作用，是细胞抵御诱导氧化应激因子的主要防御机制。该基因线粒体靶向序列中的一个基因多态性与癌症风险增加有关。这种一个碱基对的转换（-9 T>C）导致线粒体靶向序列中的缬氨酸变为丙氨酸。此外，MnSOD启动子含有一个激活蛋白-2（AP-2）结合位点，可调节MnSOD的转录。在人类肿瘤细胞系的启动子近端区域已鉴定出突变。其中一个突变（-102 C>T）已被证明会改变AP-2的结合模式，导致转录活性降低。我们研究的目的是在波兰华沙进行的一项基于人群的病例对照研究中，调查（-9 T>C）和（-102 C>T）多态性与胃癌之间可能存在的关联。
DNA取自1994年至1996年在波兰华沙进行的一项基于人群的胃癌病例对照研究。通过PCR-RFLP分析确定MnSOD -9 T>C基因型。使用TaqMan等位基因鉴别分析确定MnSOD -102 C>T基因型。
-102 C>T多态性在胃癌病例中的频率为41%（38/91），在对照中的频率为38%（50/130）（优势比[OR] 1.1，95%置信区间[CI] 0.6 - 2.1）。-9 T>C多态性在病例中的频率为44%（202/464），在对照中的频率为56%（262/464）（OR 1.1；95% CI 0.9 - 1.37）。在非吸烟者（OR 1.5；95% CI 0.7 - 2.34）和吸烟者（OR 1.1；95% CI 0.7 - 1.7）中均未观察到关联。此外，当按吸烟史程度对吸烟者进行分类时，该关联也不显著。
在波兰的一项病例对照研究中，未发现锰超氧化物歧化酶-102 C>T和-9 T>C多态性与胃癌有关联。
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