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The KRAS-Variant and miRNA Expression in RTOG Endometrial Cancer Clinical Trials 9708 and 9905
- Lee, Larissa J;
- Ratner, Elena;
- Uduman, Mohamed;
- Winter, Kathryn;
- Boeke, Marta;
- Greven, Kathryn M;
- King, Stephanie;
- Burke, Thomas W;
- Underhill, Kelly;
- Kim, Harold;
- Boulware, Raleigh J;
- Yu, Herbert;
- Parkash, Vinita;
- Lu, Lingeng;
- Gaffney, David;
- Dicker, Adam P;
- Weidhaas, Joanne
- Editor(s): Hawkins, Shannon M
- et al.
Abstract
Objective
To explore the association of a functional germline variant in the 3'-UTR of KRAS with endometrial cancer risk, as well as the association of microRNA (miRNA) signatures and the KRAS-variant with clinical characteristics and survival outcomes in two prospective RTOG endometrial cancer trials.Methods/materials
The association of the KRAS-variant with endometrial cancer risk was evaluated by case-control analysis of 467 women with type 1 or 2 endometrial cancer and 582 age-matched controls. miRNA and DNA were isolated for expression profiling and genotyping from tumor specimens of 46 women with type 1 endometrial cancer enrolled in RTOG trials 9708 and 9905. miRNA expression levels and KRAS-variant genotype were correlated with patient and tumor characteristics, and survival outcomes were evaluated by variant allele type.Results
The KRAS-variant was not significantly associated with overall endometrial cancer risk (14% controls and 17% type 1 cancers), although was enriched in type 2 endometrial cancers (24%, p = 0.2). In the combined analysis of RTOG 9708/9905, miRNA expression differed by age, presence of lymphovascular invasion and KRAS-variant status. Overall survival rates at 3 years for patients with the variant and wild-type alleles were 100% and 77% (HR 0.3, p = 0.24), respectively, favoring the variant.Conclusions
The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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