title: MNS16A tandem repeats minisatellite of human telomerase gene: a risk factor for colorectal cancer.
abstract: Telomerase reactivation and expression of human telomerase gene [human telomerase reverse transcriptase (hTERT)] are hallmarks of unlimited proliferation potential of cancer cells. A polymorphic tandem repeats minisatellite of hTERT gene, termed MNS16A was reported to influence hTERT expression. To assess the role of MNS16A as potential biomarker for colorectal cancer (CRC), we investigated for the first time the association of MNS16A genotypes with risk of colorectal polyps and CRC. In the ongoing colorectal cancer study of Austria (CORSA), 3842 Caucasian participants were recruited within a large screening project in the province Burgenland including 90 CRC cases, 308 high-risk polyps, 1022 low-risk polyps and 1822 polyp free controls verified by colonoscopy. MNS16A genotypes were determined by polymerase chain reaction from genomic DNA. Associations of MNS16A genotypes with CRC risk were estimated by logistic regression analysis computing odds ratios (ORs) and 95% confidence intervals (CIs). We identified five different variable number of tandem repeats (VNTRs) of MNS16A including VNTR-364, a newly discovered rare variant. VNTR-274 allele was associated with a 2.7-fold significantly increased risk of CRC compared with the VNTR-302 wild-type (OR = 2.69; 95% CI = 1.11-6.50; P = 0.028). In our CORSA study, the medium length VNTR-274 was identified as risk factor for CRC. Although, this population-based study herewith reports the largest cohort size concerning MNS16A thus far, further large-scale studies in diverse populations are warranted to confirm hTERT MNS16A genotype as potential biomarker for assessment of CRC risk.
authors.affiliation: Department of Medicine I, Division: Institute of Cancer Research, Comprehensive Cancer Center, Medical University Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Hofer
authors.forename: Andreas
authors.initials: A
authors.lastname: Baierl
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Feik
authors.forename: Gerhard
authors.initials: G
authors.lastname: Führlinger
authors.forename: Gernot
authors.initials: G
authors.lastname: Leeb
authors.forename: Karl
authors.initials: K
authors.lastname: Mach
authors.forename: Klaus
authors.initials: K
authors.lastname: Holzmann
authors.forename: Michael
authors.initials: M
authors.lastname: Micksche
authors.forename: Andrea
authors.initials: A
authors.lastname: Gsur
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria / Q000453:epidemiology; D001483:Base Sequence; D003111:Colonic Polyps; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D020080:Tandem Repeat Sequences / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C509186:TERT protein, human; D019098:Telomerase