Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study
Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study
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DOI：
10.1093/carcin/bgi267
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发表时间：
2006-04-01
期刊：
影响因子：
4.7
通讯作者：
Vogel, U
中科院分区：
文献类型：
--
作者：
Ravn-Haren, G;Olsen, A;Vogel, U
乳腺癌可能与氧化应激有关。据报道，乳腺癌患者的抗氧化酶活性低于健康对照，GPX 1 Pro 198 Leu多态性与肺癌和乳腺癌的风险相关。本巢式病例对照研究的目的是确定是否GPX 1 Pro 198 Leu和谷胱甘肽过氧化物酶（GPX）活性在前瞻性收集的血液样本中与绝经后妇女乳腺癌的风险和GPX活性水平是否与其他已知的乳腺癌危险因素。我们将377例女性乳腺癌病例与377例对照组进行了匹配，所有对照组都在57000名丹麦人的前瞻性“饮食，癌症和健康”研究中。GPX 1 Pro 198 Leu变异T等位基因携带者患乳腺癌的风险是非携带者的1.43倍（95%CI = 1.07-1.92）。与对照组相比，病例组的诊断前GPX活性往往较低。GPX活性与饮酒量呈正相关（P < 0.0001），变异T等位基因每增加一个拷贝，GPX活性降低5%（P = 0.0003）。酒精摄入量与C等位基因GPX活性增加相关，但与T等位基因无关。这项前瞻性研究的结果表明，GPX 1 Pro 198 Leu相关的GPX活性降低与丹麦女性患乳腺癌的风险较高有关。
Breast cancer may be related to oxidative stress. Breast cancer patients have been reported to have lower antioxidant enzyme activity than healthy controls and the polymorphism GPX1 Pro198Leu has been associated with risk of lung and breast cancer. The purpose of the present nested case-control study was to determine whether GPX1 Pro198Leu and glutathione peroxidase (GPX) activity in prospectively collected blood samples are associated with breast cancer risk among postmenopausal women and whether GPX activity levels are associated with other known breast cancer risk factors. We matched 377 female breast cancer cases with 377 controls all nested within the prospective 'Diet, Cancer and Health' study of 57 000 Danes. Carriers of the variant T-allele of GPX1 Pro198Leu were at 1.43-fold higher risk of breast cancer compared with non-carriers (95% CI = 1.07-1.92). Pre-diagnostic GPX activity tended to be lower in cases compared with controls. GPX activity was positively correlated with intake of alcohol (P < 0.0001) and the catalytic activity was lowered 5% for each additional copy of the variant T-allele (P = 0.0003). Alcohol intake was correlated with increased GPX activity for the C-allele but not for the T-allele. Results from this prospective study suggest that the GPX1 Pro198Leu-associated lowered GPX activity is associated with higher breast cancer risk among Danish women.