title: Polymorphisms in microRNA genes as predictors of clinical outcomes in colorectal cancer patients.
abstract: Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies worldwide. It is routinely cured by a 5-fluorouracil (5-FU)-based chemotherapy which improves outcomes in patients. We investigated the effect of single nucleotide polymorphisms (SNPs) in two microRNA (miRNA)-encoding genes that have been previously reported as important in prognosis in patients with stage III CRC and treated with 5-FU-based chemotherapy. Two SNPs (rs4919510 in miR-608 and rs213210 in miR-219-1) were genotyped in 1083 CRC patients recruited in the Czech Republic to evaluate their effect on clinical outcomes. Carriers of the variant T allele in rs213210 and receiving 5-FU chemotherapy were associated with a significantly worse survival [hazard ratio (HR) = 2.18; 95% confidence interval (CI): 1.20-3.98; adjusted P = 0.01] and an increased risk of relapse (HR = 1.94; 95% CI: 1.16-3.25; adjusted P = 0.01). After further stratification for tumor grading, stage III patients carrying the G allele of rs4919510 and undergoing adjuvant chemotherapy were at decreased risk of relapse (HR = 0.44; 95% CI: 0.20-0.94; adjusted P = 0.03). The present study confirms that variations in miRNA-encoding genes may be an important factor for modulating CRC prognosis and predicting therapy response.
authors.affiliation: Genomic Variation in Human Population and Complex Diseases and Molecular and Genetic Epidemiology Units, Human Genetics Foundation, 10126 Turin, Italy, Department of Medical Sciences, University of Turin, 10126 Turin, Italy, barbara.pardini@hugef-torino.org.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pardini
authors.affiliation: Genomic Variation in Human Population and Complex Diseases and Molecular and Genetic Epidemiology Units, Human Genetics Foundation, 10126 Turin, Italy, Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Rosa
authors.affiliation: Genomic Variation in Human Population and Complex Diseases and Molecular and Genetic Epidemiology Units, Human Genetics Foundation, 10126 Turin, Italy, Department of Molecular Biology of Cancer, Institute of Experimental Medicine, 14200 Prague, Czech Republic.
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.affiliation: Department of Molecular Biology of Cancer, Institute of Experimental Medicine, 14200 Prague, Czech Republic, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, 12108 Prague, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Vymetalkova
authors.affiliation: Division of Cancer Prevention & Population Sciences, The University of Texas MD Anderson Cancer Center, 77030 Houston, TX, USA.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Division of Cancer Prevention & Population Sciences, The University of Texas MD Anderson Cancer Center, 77030 Houston, TX, USA.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Genomic Variation in Human Population and Complex Diseases and Molecular and Genetic Epidemiology Units, Human Genetics Foundation, 10126 Turin, Italy, Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
authors.forename: Cornelia
authors.initials: C
authors.lastname: di Gaetano
authors.affiliation: Department of Surgery, First Faculty of Medicine, Charles University, 12108 Prague, Czech Republic, Department of Oncology, Thomayer University Hospital, Prague, Czech Republic and.
authors.forename: Tomas
authors.initials: T
authors.lastname: Buchler
authors.affiliation: Department of Oncology, First Faculty of Medicine, Charles University, 12108 Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Novotny
authors.affiliation: Genomic Variation in Human Population and Complex Diseases and Molecular and Genetic Epidemiology Units, Human Genetics Foundation, 10126 Turin, Italy, Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matullo
authors.affiliation: Department of Molecular Biology of Cancer, Institute of Experimental Medicine, 14200 Prague, Czech Republic, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, 12108 Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C578248:MIRN219 microRNA, human; C000591804:MIRN608 microRNA, human; D035683:MicroRNAs; D005472:Fluorouracil