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The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905 . 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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Outcome_Physical
overall endometrial cancer risk
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Outcome_Other
9708/9905 , miRNA expression
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Outcome_Other
status
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Outcome_Mortality
Overall survival rates
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Participant_Condition
endometrial cancer
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Participant_Sample-size
467
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Participant_Sex
women
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Participant_Condition
type 1 or 2 endometrial cancer
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Participant_Condition
tumor
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Participant_Sample-size
46
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Participant_Condition
type 1 endometrial cancer
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Participant_Condition
variant and wild-type alleles