Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens
Autor: | Francesca Migheli, Gabriella Fontanini, Angela Lopomo, Massimo Seccia, Adele Servadio, Annalisa Legitimo, Elisa Sensi, Rita Consolini, Massimo Chiarugi, Fabio Coppedè, Giuseppe Zocco, Lucia Migliore, Alessandra Failli, Roberto Spisni |
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Rok vydání: | 2014 |
Předmět: |
Male
Cancer Research Colon Colorectal cancer folate metabolism Biology hMLH1 CDKN2A Folic Acid Intestinal mucosa medicine Humans Epigenetics Intestinal Mucosa Promoter Regions Genetic Homocysteine neoplasms Molecular Biology Aged Aged 80 and over Colorectal Cancer Polymorphism Genetic DNA methylation epigenetics Rectum RASSF1A Methylation Middle Aged medicine.disease MTRR digestive system diseases APC Vitamin B 12 Colorectal Cancer epigenetics DNA methylation folate metabolism polymorphisms APC MGMT CDKN2A hMLH1 RASSF1A Case-Control Studies Methylenetetrahydrofolate reductase Cancer research biology.protein Female Colorectal Neoplasms polymorphisms MGMT Biomarkers Metabolic Networks and Pathways Research Paper |
Zdroj: | Epigenetics. 9:621-633 |
ISSN: | 1559-2308 1559-2294 |
Popis: | We evaluated the promoter methylation levels of the APC, MGMT, hMLH1, RASSF1A and CDKN2A genes in 107 colorectal cancer (CRC) samples and 80 healthy adjacent tissues. We searched for correlation with both physical and pathological features, polymorphisms of folate metabolism pathway genes (MTHFR, MTRR, MTR, RFC1, TYMS, and DNMT3B), and data on circulating folate, vitamin B12 and homocysteine, which were available in a subgroup of the CRC patients. An increased number of methylated samples were found in CRC respect to adjacent healthy tissues, with the exception of APC, which was also frequently methylated in healthy colonic mucosa. Statistically significant associations were found between RASSF1A promoter methylation and tumor stage, and between hMLH1 promoter methylation and tumor location. Increasing age positively correlated with both hMLH1 and MGMT methylation levels in CRC tissues, and with APC methylation levels in the adjacent healthy mucosa. Concerning gender, females showed higher hMLH1 promoter methylation levels with respect to males. In CRC samples, the MTR 2756AG genotype correlated with higher methylation levels of RASSF1A, and the TYMS 1494 6bp ins/del polymorphism correlated with the methylation levels of both APC and hMLH1. In adjacent healthy tissues, MTR 2756AG and TYMS 1494 6bp del/del genotypes correlated with APC and MGMT promoter methylation, respectively. Low folate levels were associated with hMLH1 hypermethylation. Present results support the hypothesis that DNA methylation in CRC depends from both physiological and environmental factors, with one-carbon metabolism largely involved in this process. |
Databáze: | OpenAIRE |
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