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Pharmacogenomics J. 2015 Oct;15(5):391-6. doi: 10.1038/tpj.2015.2. Epub 2015 Feb 10.

LGR5 rs17109924 is a predictive genetic biomarker for time to recurrence in patients with colon cancer treated with 5-fluorouracil-based adjuvant chemotherapy.

Author information

1
Division of Clinical Oncology, Department of Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, Graz, Austria.
2
Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
3
Institute of Pathology, Medical University of Graz, Graz, Austria.
4
Department of Pathology, General Hospital Graz West, Graz, Austria.
5
Department of Pathology, General Hospital of Leoben, Leoben, Austria.
6
Clinical Institute of Medical and Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
7
Division of Clinical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.

Abstract

We recently found variants in cancer stem cell genes (CD44, ALCAM and LGR5) significantly associated with increased time to recurrence (TTR) in patients with stage III and high-risk stage II colon cancer treated with 5-fluorouracil (5-FU)-based chemotherapy. In this study, we validated these genetic biomarkers in a large and independent patient cohort (n=599). Patients who received 5-FU-based adjuvant chemotherapy (n=391) carrying at least one C allele in LGR5 rs17109924 had a significantly increased TTR compared with patients carrying the homozygous T/T variant (HR 0.38, 95%CI 0.19-0.79; P=0.006). In patients treated with surgery alone (n=208), no association between LGR rs17109924 and TTR was found (P=0.728). In the multivariate Cox-analysis, LGR5 rs17109924 remained statistically significant (HR 0.38, 95%CI 0.18-0.78; P=0.008) for patients who received adjuvant chemotherapy. We confirmed in a large and independent study cohort that LGR5 rs17109924 is a predictive genetic biomarker for TTR in patients with colon cancer treated with 5-FU-based adjuvant chemotherapy.

PMID:
25665511
PMCID:
PMC4762902
DOI:
10.1038/tpj.2015.2
[Indexed for MEDLINE]
Free PMC Article

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