title: The cyclin D1 (CCND1) rs9344 G>A polymorphism predicts clinical outcome in colon cancer patients treated with adjuvant 5-FU-based chemotherapy.
abstract: Recent evidence indicates a potential prognostic and predictive value for germline polymorphisms in genes involved in cell cycle control. We investigated the effect of cyclin D1 (CCND1) rs9344 G>A in stage II/III colon cancer patients and validated the findings in an independent study cohort. For evaluation and validation set, a total of 264 and 234 patients were included. Patients treated with 5-fluorouracil-based chemotherapy, carrying the CCND1 rs9344 A/A genotype had significantly decreased time-to-tumor recurrence (TTR) in univariate analysis and multivariate analysis (hazard ratio (HR) 2.47; 95% confidence interval (CI) 1.16-5.29; P=0.019). There was no significant association between CCND1 rs9344 G>A and TTR in patients with curative surgery alone. In the validation set, the A allele of CCND1 rs9344 G>A remained significantly associated with decreased TTR in univariate and multivariate analyses (HR 1.94; 95% CI 1.05-3.58; P=0.035). CCND1 rs9344 G>A may be a predictive and/or prognostic biomarker in stage II/III colon cancer patients, however, prospective trials are warranted to confirm our findings.
authors.affiliation: 1] Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria [2] Research Unit Genetic Epidemiology and Pharmacogenetics, Medical University of Graz, Graz, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Absenger
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Benhaim
authors.affiliation: 1] Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria [2] Research Unit Genetic Epidemiology and Pharmacogenetics, Medical University of Graz, Graz, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Szkandera
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.affiliation: Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Labonte
authors.affiliation: Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Pichler
authors.affiliation: 1] Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria [2] Research Unit Genetic Epidemiology and Pharmacogenetics, Medical University of Graz, Graz, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Stotz
authors.affiliation: Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Samonigg
authors.affiliation: 1] Research Unit Genetic Epidemiology and Pharmacogenetics, Medical University of Graz, Graz, Austria [2] Clinical Institute of Medical and Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Renner
authors.affiliation: 1] Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria [2] Research Unit Genetic Epidemiology and Pharmacogenetics, Medical University of Graz, Graz, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Gerger
authors.affiliation: 1] Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA [2] USC Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: C530104:CCND1 protein, human; D019938:Cyclin D1; D005472:Fluorouracil