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PLoS One. 2014 Apr 14;9(4):e94167. doi: 10.1371/journal.pone.0094167. eCollection 2014.

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

Author information

1
Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
2
Department of Gynecologic Oncology, Yale University, New Haven, Connecticut, United States of America.
3
Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, United States of America.
4
Statistical Center, Radiation Therapy Oncology Group (RTOG), Philadelphia, Pennsylvania, United States of America.
5
Department of Radiation Oncology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina, United States of America.
6
Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
7
Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
8
Department of Radiation Oncology, Benefis Sletten Cancer Institute, Great Falls, Montana, United States of America.
9
Department of Radiation Oncology, Wayne State University Karamanos Cancer Center, Detroit, Michigan, United States of America.
10
Radiation Oncology, South Carolina Oncology Associates, Columbia, South Carolina, United States of America.
11
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.
12
Department of Pathology, Yale University, New Haven, Connecticut, United States of America.
13
Department of Chronic Disease and Epidemiology, Yale University, New Haven, Connecticut, United States of America.
14
Department of Radiation Oncology, University of Utah Huntsman Cancer Hospital, Salt Lake City, Utah, United States of America.
15
Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States of America.
16
Department of Therapeutic Radiology, Yale University, New Haven, Connecticut, United States of America.

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%, pā€Š=ā€Š0.2). 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, pā€Š=ā€Š0.24), 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.

PMID:
24732316
PMCID:
PMC3986055
DOI:
10.1371/journal.pone.0094167
[Indexed for MEDLINE]
Free PMC Article

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