p16INK4a gene promoter hypermethylation in mucosa as a prognostic factor for patients with colorectal cancer.

Molecular Medicine
Yvonne WettergrenBengt Gustavsson

Abstract

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...Continue Reading

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Citations

Nov 7, 2012·International Journal of Oncology·Torbjörn K NilssonXiao-Feng Sun
Sep 14, 2011·Clinical Medicine Insights. Oncology·Kristoffer Derwinger, Bengt Gustavsson
Apr 15, 2011·Journal of Biomedicine & Biotechnology·Lucia MiglioreFabio Coppedè
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Mar 23, 2018·Clinical Epigenetics·Muriel X G DrahtKim M Smits
Jul 1, 2020·Cells·Klara CervenaVeronika Vymetalkova

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