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p16(INK4a) Gene Pro...
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Wettergren, Yvonne,1957Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences,University of Gothenburg
(author)
p16(INK4a) Gene Promoter Hypermethylation in Mucosa as a Prognostic Factor for Patients with Colorectal Cancer.
- Article/chapterEnglish2008
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LIBRIS-ID:oai:gup.ub.gu.se/70798
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https://gup.ub.gu.se/publication/70798URI
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https://doi.org/10.2119/2007-00096.WettergrenDOI
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https://research.chalmers.se/publication/70798URI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Low gene expression of folylpolyglutamate synthase (FPGS) in colorectal mucosa correlates with low folate levels and poor survival of colorectal cancer (CRC) patients. Because gene-specific hypermethylation is affected by the folate level, the hypermethylation status in mucosa may also be linked to clinical outcome of CRC patients. The tumor suppressor gene p16INK4a (p16) regulates the cell cycle and angiogenic switch. In human neoplastic tissues, the main mechanism of p16 inactivation is promoter methylation. The aim of the study was to determine whether hypermethylation of the p16 promoter could be detected in mucosa of CRC patients (n = 181) and to analyze if hypermethylation was related to survival. The relation between p16 hypermethylation and expression of FPGS and two other folate-associated genes, reduced folate carrier 1 (RFC-1), and thymidylate synthase (TS), was analyzed (n = 63). The results showed that p16 was hypermethylated in 65 (36%) of the mucosa samples and that hypermethylation was age-related (P = 0.029). After adjustment for known risk factors, Cox regression analysis showed that Dukes' A-C patients with p16 hypermethylation in mucosa had an increased risk of cancer-related death (hazard ratio = 2.9, P= 0.007) and shorter disease-free survival (hazard ratio = 2.5, P = 0.015) compared with patients with no p16 hypermethylation. RFC-1 and FPGS gene expression levels were significantly correlated in patients lacking p16 hypermethylation in mucosa (P = 0.0003), but not at all correlated in patients having hypermethylation in mucosa (P = 1.0). In conclusion, p16 hypermethylation in mucosa of CRC patients was identified as an independent prognostic parameter for cancer-specific survival as well as an independent predictor of DFS. The results suggest that there might be a connection between folate-associated gene expression and p16 methylation status.
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Odin, Elisabeth,1955Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences,University of Gothenburg(Swepub:gu)xodiel
(author)
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Nilsson, Staffan,1956Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, matematisk statistik,Department of Mathematical Sciences, Mathematical Statistics,Chalmers tekniska högskola,Chalmers University of Technology,University of Gothenburg(Swepub:cth)staffan
(author)
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Carlsson, Göran,1951Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences,University of Gothenburg(Swepub:gu)xcagor
(author)
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Gustavsson, Bengt,1947Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences,University of Gothenburg(Swepub:gu)xguben
(author)
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Göteborgs universitetInstitutionen för kliniska vetenskaper
(creator_code:org_t)
Related titles
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In:Molecular medicine14:7-8, s. 412-4211076-15511528-3658
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