Yuan Cunzhong, Liu Xiaoyan, Liu Xiaolin, Yang Ning, Liu Zhenping, Yan Shi, Shen Keng, Kong Beihua
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China; Gynecologic Oncology Key Laboratory of Shandong Province, Qilu Hospital of Shandong University, Ji'nan, Shandong, P.R. China.
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
PLoS One. 2015 Sep 30;10(9):e0138692. doi: 10.1371/journal.pone.0138692. eCollection 2015.
GADD45A (growth arrest and DNA damage 45 A) is the first stress-inducible gene identified to be a target of p53. However, no studies to date have assessed variants of the GADD45 gene and their potential relationship to tumor susceptibility. We investigated the association of the GADD45A (1506T>C) polymorphism with ovarian cancer development in 258 ovarian cancer patients and 332 age-matched healthy women as controls using sequence analysis. We found a statistically significant difference in the GADD45A (1506T>C) genotype distributions between the case and control groups (TT vs. TC vs. CC, P = 0.0021) and found that variant 1506T>C was significantly associated with an increased risk of ovarian cancer (P<0.001, OR = 1.71, 95% CI [1.28-2.29]). We observed a statistically significant effect between tumor histology (P = 0.032) and CA125 status (P = 0.021). Carrying the C allele (TC+CC) was associated with an increased risk of positive CA125 (OR = 3.20, 95% CI [1.15-8.71). Carrying the T allele (TT+TC) showed a significant correlation with both higher GADD45A mRNA expression and longer ovarian cancer RFS (relapse-free survival) and OS (overall survival). We are the first group to demonstrate that the GADD45A (1506T>C) polymorphism is associated with ovarian cancer susceptibility and prognosis. These data suggest that GADD45A (1506T>C) is a new tumor susceptibility gene and could be a useful molecular marker for assessing ovarian cancer risk and for predicting ovarian cancer patient prognosis.
生长停滞和DNA损伤诱导蛋白45A（GADD45A）是首个被鉴定为p53靶点的应激诱导基因。然而，迄今为止尚无研究评估GADD45基因的变异及其与肿瘤易感性的潜在关系。我们采用序列分析方法，对258例卵巢癌患者和332例年龄匹配的健康女性作为对照进行研究，以探讨GADD45A（1506T>C）多态性与卵巢癌发生的关联。我们发现病例组和对照组之间GADD45A（1506T>C）基因型分布存在统计学显著差异（TT与TC与CC，P = 0.0021），并发现1506T>C变异与卵巢癌风险增加显著相关（P<0.001，OR = 1.71，95%CI[1.28 - 2.29]）。我们观察到肿瘤组织学（P = 0.032）和CA125状态（P = 0.021）之间存在统计学显著影响。携带C等位基因（TC + CC）与CA125阳性风险增加相关（OR = 3.20，95%CI[1.15 - 8.71]）。携带T等位基因（TT + TC）与更高的GADD45A mRNA表达以及更长的卵巢癌无复发生存期（RFS）和总生存期（OS）均显示出显著相关性。我们是首个证明GADD45A（1506T>C）多态性与卵巢癌易感性及预后相关的研究团队。这些数据表明，GADD45A（1506T>C）是一个新的肿瘤易感基因，可能是评估卵巢癌风险和预测卵巢癌患者预后的有用分子标志物。
