Am J Cancer Res. 2012;2(3):298-308. Epub 2012 Apr 21.
Epithelial ovarian cancer is a malignancy with high rate of death due to an advanced disease at diagnosis and frequent relapse after chemotherapy. Nowadays, there is a lack of knowledge for clear risk factors and predictive and/or prognostic genetic markers although genomic alterations such as mutations in p53, PTEN, BRCA1/BRCA2, HER2, KRAS and PI3K genes have been associated to this pathology. A genomic variant in the 3' untraslated region of cancer related gene KRAS, is able to disrupt the let-7 miRNA binding site. The SNP, commonly named KRAS-LCS6, determines the substitution of the more abundant T-allele to a G-allele which was observed to increase the KRAS expression and in turn to activate the downstream pathway at higher levels if compared to the T-allele. In this study we assessed the role of the KRAS-LCS6 polymorphism (rs61764370) in 97 early (stages I and II) and 232 advanced (stages III and IV) ovarian cancer patients in order to associate this SNP to any physiopathological characteristic of the patients cohort, including progression free survival and overall survival, with a follow up data longer than ten years. Our data indicate that KRAS-LCS6 polymorphism is not relevant in ovarian cancer, in fact, in our cohort of patients, is not associated to any outcome or physiopathological characteristic.
上皮性卵巢癌是一种恶性肿瘤，由于诊断时疾病已处于晚期以及化疗后频繁复发，死亡率很高。尽管 p53、PTEN、BRCA1/BRCA2、HER2、KRAS 和 PI3K 等基因的突变与这种病理学有关，但目前对于明确的风险因素以及预测和/或预后遗传标志物的了解仍然不足。癌症相关基因 KRAS 的 3'非翻译区的基因组变异能够破坏 let-7 miRNA 结合位点。这种常见的 SNP 被命名为 KRAS-LCS6，它决定了更丰富的 T 等位基因被 G 等位基因取代，与 T 等位基因相比，这会增加 KRAS 的表达，并反过来以更高的水平激活下游途径。在这项研究中，我们评估了 KRAS-LCS6 多态性（rs61764370）在 97 例早期（I 期和 II 期）和 232 例晚期（III 期和 IV 期）卵巢癌患者中的作用，以将该 SNP 与患者队列的任何生理病理特征相关联，包括无进展生存期和总生存期，并进行了超过十年的随访数据。我们的数据表明，KRAS-LCS6 多态性与卵巢癌无关，实际上，在我们的患者队列中，它与任何结果或生理病理特征都没有关联。
