Rodrigues Patricia, Furriol Jessica, Bermejo Begoña, Chaves Felipe Javier, Lluch Ana, Eroles Pilar
Institute of Health Research INCLIVA, Av. Blasco Ibañez, 17, Valencia 46010, Spain.
Int J Mol Sci. 2012 Dec 5;13(12):16500-13. doi: 10.3390/ijms131216500.
Diverse polymorphisms have been associated with the predisposition to develop cancer. On fewer occasions, they have been related to the evolution of the disease and to different responses to treatment. Previous studies of our group have associated polymorphisms on genes related to oxidative stress (rs3736729 on GCLC and rs207454 on XDH) and DNA damage repair (rs1052133 on OGG1) with a predisposition to develop breast cancer. In the present work, we have evaluated the hypothesis that these polymorphisms also play a role in a patient's survival. A population-based cohort study of 470 women diagnosed with primary breast cancer and a median follow up of 52.44 months was conducted to examine the disease-free and overall survival in rs3736729, rs207454 and rs1052133 genetic variants. Adjusted Cox regression analysis was used to that end. The Kaplan-Meier analysis shows that rs3736729 on GCLC presents a significant association with disease-free survival and overall survival. The polymorphisms rs1052133 on OGG1 and rs207454 on XDH show a trend of association with overall survival. The analysis based on hormonal receptor status revealed a stronger association. The CC genotype on rs207454 (XDH) was significantly associated with lower time of disease free survival (p = 0.024) in progesterone receptor negative (PGR-) patients and rs3736729 (GCLC) was significantly associated with disease free survival (p = 0.001) and overall survival (p = 0.012) in the subgroup of estrogen receptor negative (ER-) patients. This work suggests that unfavorable genetic variants in the rs207454 (XDH) and rs3736729 (GCLC) polymorphisms may act as predictors of the outcome in negative progesterone receptor and negative estrogen receptor breast cancer patients, respectively.
多种多态性与患癌易感性相关。在较少情况下，它们与疾病的进展以及对治疗的不同反应有关。我们团队之前的研究已将与氧化应激相关基因（GCLC上的rs3736729和XDH上的rs207454）以及DNA损伤修复相关基因（OGG1上的rs1052133）的多态性与患乳腺癌的易感性联系起来。在本研究中，我们评估了这些多态性也在患者生存中起作用的假设。开展了一项基于人群的队列研究，纳入470例诊断为原发性乳腺癌的女性，中位随访时间为52.44个月，以研究rs3736729、rs207454和rs1052133基因变异的无病生存期和总生存期。为此采用了校正后的Cox回归分析。Kaplan-Meier分析表明，GCLC上的rs3736729与无病生存期和总生存期存在显著关联。OGG1上的rs1052133和XDH上的rs207454多态性显示出与总生存期的关联趋势。基于激素受体状态的分析显示出更强的关联性。rs207454（XDH）的CC基因型在孕激素受体阴性（PGR-）患者中与无病生存期较短显著相关（p = 0.024），而rs3736729（GCLC）在雌激素受体阴性（ER-）患者亚组中与无病生存期（p = 0.001）和总生存期（p = 0.012）显著相关。这项研究表明，rs207454（XDH）和rs3736729（GCLC）多态性中的不良基因变异可能分别作为孕激素受体阴性和雌激素受体阴性乳腺癌患者预后的预测指标。
