KRas-LCS6 Polymorphism Does Not Impact on Outcomes in Ovarian Cancer

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.

Keywords: KRAS; LCS6; let-7; miRNA; ovarian cancer; rs61764370.