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The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905.

  • Author(s): 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
  • 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.

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