title: The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905.
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
  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.
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Larissa J
authors.initials: LJ
authors.lastname: Lee
authors.affiliation: Department of Gynecologic Oncology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Elena
authors.initials: E
authors.lastname: Ratner
authors.affiliation: Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Uduman
authors.affiliation: Statistical Center, Radiation Therapy Oncology Group (RTOG), Philadelphia, Pennsylvania, United States of America.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Winter
authors.affiliation: Department of Gynecologic Oncology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Marta
authors.initials: M
authors.lastname: Boeke
authors.affiliation: Department of Radiation Oncology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina, United States of America.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Greven
authors.affiliation: Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Stephanie
authors.initials: S
authors.lastname: King
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Burke
authors.affiliation: Department of Radiation Oncology, Benefis Sletten Cancer Institute, Great Falls, Montana, United States of America.
authors.forename: Kelly
authors.initials: K
authors.lastname: Underhill
authors.affiliation: Department of Radiation Oncology, Wayne State University Karamanos Cancer Center, Detroit, Michigan, United States of America.
authors.forename: Harold
authors.initials: H
authors.lastname: Kim
authors.affiliation: Radiation Oncology, South Carolina Oncology Associates, Columbia, South Carolina, United States of America.
authors.forename: Raleigh J
authors.initials: RJ
authors.lastname: Boulware
authors.affiliation: Department of Chronic Disease and Epidemiology, Yale University, New Haven, Connecticut, United States of America; Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Pathology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Vinita
authors.initials: V
authors.lastname: Parkash
authors.affiliation: Department of Chronic Disease and Epidemiology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Lingeng
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, University of Utah Huntsman Cancer Hospital, Salt Lake City, Utah, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Gaffney
authors.affiliation: Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States of America.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Dicker
authors.affiliation: Department of Therapeutic Radiology, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Joanne
authors.initials: J
authors.lastname: Weidhaas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012307:Risk Factors; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
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