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氧化应激相关酶基因多态性与非吸烟、非饮酒台湾女性乳腺癌易感性的关系:一项病例对照研究。

Oxidative stress-related enzyme gene polymorphisms and susceptibility to breast cancer in non-smoking, non-alcohol-consuming Taiwanese women: a case-control study.

机构信息

Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

出版信息

Ann Clin Biochem. 2012 Mar;49(Pt 2):152-8. doi: 10.1258/acb.2011.011098. Epub 2011 Nov 30.

Abstract

BACKGROUND

Mitochondrial manganese superoxide dismutase (MnSOD) converts superoxide anion into H(2)O(2), which is neutralized sequentially by either catalase (CAT) or glutathione peroxidase 1 (Gpx 1) into water or converted into highly reactive hypochlorous acid by myeloperoxidase (MPO). We hypothesize that gene variants for these enzymes might be associated with the risk of breast cancer in non-smoking, non-alcohol-consuming women.

METHODS

Genotypes of oxidative stress-related enzymes (MnSOD1183T>C, MPO-463G>A, GPx1Pro198Leu and CAT-262C>T) were analysed in 260 non-smoking and non-alcohol-consuming female patients with breast cancer and 224 habit-matched controls.

RESULTS

Subjects with the MnSOD1183T>C C carrier or those with the GPx1Pro198Leu CT genotype had significantly decreased age-adjusted risks (odds ratio [OR]: 0.56 and 0.16 with 95% confidence intervals [95% CI]: 0.38-0.83 and 0.08-0.29, respectively) for breast cancer. Certain combined genotypes of the polymorphisms also significantly modulated the age-adjusted risk.

CONCLUSIONS

We conclude that oxidative stress-related enzyme genetic variants, especially GPx1Pro198Leu CT, modify the risk of breast cancer development in non-smoking and non-alcohol-consuming women. The role of unidentified environmental factors predisposing to breast cancer development through an oxidative stress mechanism merits further investigation.

摘要

背景

线粒体锰超氧化物歧化酶(MnSOD)将超氧阴离子转化为 H₂O₂,然后过氧化氢被过氧化氢酶(CAT)或谷胱甘肽过氧化物酶 1(Gpx 1)依次中和为水,或被髓过氧化物酶(MPO)转化为高反应性次氯酸。我们假设这些酶的基因变异可能与不吸烟、不饮酒的女性患乳腺癌的风险相关。

方法

分析了 260 名不吸烟、不饮酒的女性乳腺癌患者和 224 名习惯匹配对照者的氧化应激相关酶(MnSOD1183T>C、MPO-463G>A、Gpx1Pro198Leu 和 CAT-262C>T)的基因型。

结果

MnSOD1183T>C C 携带者或 Gpx1Pro198Leu CT 基因型的受试者乳腺癌的年龄校正风险显著降低(比值比[OR]:0.56 和 0.16,95%置信区间[95%CI]:0.38-0.83 和 0.08-0.29)。某些多态性的组合基因型也显著调节了年龄校正的风险。

结论

我们得出结论,氧化应激相关酶遗传变异,特别是 Gpx1Pro198Leu CT,改变了不吸烟、不饮酒的女性乳腺癌的发病风险。需要进一步研究通过氧化应激机制导致乳腺癌发生的未知环境因素的作用。

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