Bica Claudia Giuliano, da Silva Leonardo Leiria de Moura, Toscani Nadima Vieira, Zettler Cláudio Galleano, Gottlieb Maria Gabriela do Valle, Alexandre Cláudio Osmar Pereira, Graudenz Márcia Silveira, Mânica da Cruz Ivana Beatrice
Programa de Pós-Graduação em Patologia, Universidade Federal de Ciências Médicas de Porto Alegre, Rua Sarmento Leite, 245, Porto Alegre 90050-170, Brazil.
Cancer Genet Cytogenet. 2010 Jan 15;196(2):153-8. doi: 10.1016/j.cancergencyto.2009.09.011.
We studied the possible association between Ala16Val manganese-dependent superoxide dismutase (MnSOD) gene genotypes and breast cancer lymph node status because previous investigations suggested an association between the AA genotype and breast cancer. We included 281 women (188 controls and 93 cases of invasive breast cancer with axillary lymph node metastasis (LN+) and without lymph node metastasis (LN-). DNA was extracted from paraffin-embedded tumor tissue or peripheral blood leukocytes, and MnSOD polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism techniques. In addition, the immunohistochemical profile (p53, Ki-67 and estrogen/progesterone receptors) was also compared between invasive breast cancer groups and different MnSOD genotypes. The frequency of the VV genotype was higher in the LN+ group than in the control and LN- groups (chi(2)=5.081, P=0.02). Subjects with LN+ breast cancer (LN+ group) showed a higher incidence of VV genotype carriers associated with positive Ki-67 marker. Subjects with LN+ breast cancer (LN+ group) showed a higher incidence of VV genotype carriers associated with negative p53 marker. Despite the fact that the AA genotype is well established as being associated with an increased risk of breast cancer, the VV genotype may be associated with a higher metastatic potential, suggesting that MnSOD imbalance is the condition associated with carcinogenesis.
我们研究了丙氨酸16缬氨酸锰依赖性超氧化物歧化酶（MnSOD）基因基因型与乳腺癌淋巴结状态之间可能存在的关联，因为先前的研究表明AA基因型与乳腺癌之间存在关联。我们纳入了281名女性（188名对照者以及93例伴有腋窝淋巴结转移（LN+）和无淋巴结转移（LN-）的浸润性乳腺癌患者）。从石蜡包埋的肿瘤组织或外周血白细胞中提取DNA，并通过聚合酶链反应-限制性片段长度多态性技术确定MnSOD多态性。此外，还比较了浸润性乳腺癌组与不同MnSOD基因型之间的免疫组化特征（p53、Ki-67和雌激素/孕激素受体）。LN+组中VV基因型的频率高于对照组和LN-组（χ2=5.081，P=0.02）。伴有LN+乳腺癌的受试者（LN+组）中，与Ki-67标记阳性相关的VV基因型携带者发生率更高。伴有LN+乳腺癌的受试者（LN+组）中，与p53标记阴性相关的VV基因型携带者发生率更高。尽管AA基因型已被充分证实与乳腺癌风险增加相关，但VV基因型可能与更高的转移潜能相关，这表明MnSOD失衡是与致癌作用相关的情况。
