Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic.
Int J Cancer. 2012 Jan 15;130(2):338-48. doi: 10.1002/ijc.26006. Epub 2011 Apr 20.
Associations of transcript levels of oxidative stress-modifying genes SOD2, SOD3, NQO1 and NQO2 and their functional single nucleotide polymorphisms (SNPs) rs4880, rs1799895, rs2536512, rs699473, rs1800566 and rs1143684 with prognosis of breast cancer patients were studied. SNPs were assessed by allelic discrimination in a cohort of 321 breast cancer patients from the Czech Republic. Transcript levels were determined by real-time polymerase chain reaction (PCR) with absolute quantification in tumor and adjacent non-neoplastic control tissues. Both genotypes and transcript levels were then compared with available clinical data on patients. Patients carrying low activity allele Leu in NQO2 rs1143684 had a greater incidence of stage 0 or I disease (i.e., better prognosis) than patients with the Phe/Phe genotype. This association was more evident in patients without expression of progesterone receptors (p = 0.031). Patients carrying the Thr allele in SOD3 rs2536512 SNP had a significantly greater incidence of tumors expressing estrogen receptors than patients carrying the Ala/Ala genotype (p = 0.007). SOD3 transcript level was significantly higher in grade 1 or 2 tumors than in grade 3 tumors (p = 0.006). Patients carrying T allele in SOD3 rs699473 SNP had significantly poorer progression-free survival (PFS) than patients carrying the CC genotype (p = 0.038). The same applied to the subgroup of patients treated by hormonal regimens (p = 0.021). Patients carrying the high activity Ala/Ala genotype in SOD2 (rs4880) had significantly poorer PFS than Val allele carriers in the group treated by cyclophosphamide but not hormonal regimens (p = 0.004). Our results suggest that NQO2, SOD2 and SOD3 may significantly modify prognosis of breast cancer patients and that their significance should be further characterized.
研究了氧化应激修饰基因 SOD2、SOD3、NQO1 和 NQO2 的转录水平及其功能单核苷酸多态性（SNP）rs4880、rs1799895、rs2536512、rs699473、rs1800566 和 rs1143684 与乳腺癌患者预后的关系。在捷克共和国的一个 321 例乳腺癌患者队列中，通过等位基因鉴别评估了 SNP。通过肿瘤和相邻非肿瘤对照组织中的实时聚合酶链反应（PCR）进行绝对定量确定转录水平。然后将基因型和转录水平与患者的可用临床数据进行比较。与携带 NQO2 rs1143684 低活性等位基因 Leu 的患者相比，携带 Phe/Phe 基因型的患者的 0 期或 I 期疾病（即更好的预后）发生率更高。在缺乏孕激素受体表达的患者中，这种相关性更为明显（p = 0.031）。与携带 Ala/Ala 基因型的患者相比，携带 SOD3 rs2536512 SNP 的 Thr 等位基因的患者肿瘤表达雌激素受体的发生率显著更高（p = 0.007）。SOD3 转录水平在 1 级或 2 级肿瘤中显著高于 3 级肿瘤（p = 0.006）。与携带 CC 基因型的患者相比，携带 SOD3 rs699473 SNP 的 T 等位基因的患者无进展生存期（PFS）显著更差（p = 0.038）。对于接受激素治疗方案的患者亚组也同样适用（p = 0.021）。与携带 Val 等位基因的患者相比，在接受环磷酰胺治疗但不接受激素治疗方案的患者中，携带 SOD2（rs4880）高活性 Ala/Ala 基因型的患者 PFS 显著更差（p = 0.004）。我们的结果表明，NQO2、SOD2 和 SOD3 可能显著改变乳腺癌患者的预后，其意义应进一步阐明。
