title: LGR5 rs17109924 is a predictive genetic biomarker for time to recurrence in patients with colon cancer treated with 5-fluorouracil-based adjuvant chemotherapy.
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.
authors: Division of Clinical Oncology, Department of Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, Graz, Austria.
authors: J
authors: J
authors: Szkandera
authors: Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
authors: S
authors: S
authors: Herzog
authors: Division of Clinical Oncology, Department of Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, Graz, Austria.
authors: M
authors: M
authors: Pichler
authors: Division of Clinical Oncology, Department of Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, Graz, Austria.
authors: V
authors: V
authors: Stiegelbauer
authors: Division of Clinical Oncology, Department of Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, Graz, Austria.
authors: M
authors: M
authors: Stotz
authors: Division of Clinical Oncology, Department of Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, Graz, Austria.
authors: R
authors: R
authors: Schaberl-Moser
authors: Division of Clinical Oncology, Department of Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, Graz, Austria.
authors: H
authors: H
authors: Samonigg
authors: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors: M
authors: M
authors: Asslaber
authors: Department of Pathology, General Hospital Graz West, Graz, Austria.
authors: S
authors: S
authors: Lax
authors: Department of Pathology, General Hospital of Leoben, Leoben, Austria.
authors: G
authors: G
authors: Leitner
authors: Clinical Institute of Medical and Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors: W
authors: W
authors: Renner
authors: Division of Clinical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors: H-J
authors: HJ
authors: Lenz
authors: Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
authors: A
authors: A
authors: Berghold
authors: Division of Clinical Oncology, Department of Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, Graz, Austria.
authors: A
authors: A
authors: Gerger
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled; D005472:Fluorouracil