Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker

Autor: Corrado Zenesini, Vittorio Simeon, Francesca Maffei, Juan Manuel Zolezzi Moraga, Giulia Sammarini, Patrizia Hrelia, Sabrina Angelini, Davide Festi, Gloria Ravegnini, Muriel Assunta Musti
Přispěvatelé: Ravegnini, Gloria, Zolezzi Moraga, Juan Manuel, Maffei, Francesca, Musti, Muriel, Zenesini, Corrado, Simeon, Vittorio, Sammarini, Giulia, Festi, Davide, Hrelia, Patrizia, Angelini, Sabrina
Rok vydání: 2015
Předmět:
Male
Colorectal cancer
SEPT9 methylation
micronuclei
genetic polymorphisms
colorectal cancer
lcsh:Chemistry
Gene Frequency
INDEL Mutation
Genotype
Odds Ratio
genetic polymorphism
Promoter Regions
Genetic
lcsh:QH301-705.5
Spectroscopy
Aged
80 and over
General Medicine
Methylation
Middle Aged
Computer Science Applications
Adenomatous Polyposis Coli
Micronucleus test
DNA methylation
Female
Colorectal Neoplasms
Biology
Polymorphism
Single Nucleotide
Catalysis
Article
Inorganic Chemistry
Folic Acid
Cell Line
Tumor
medicine
Biomarkers
Tumor
Humans
Physical and Theoretical Chemistry
Allele
Molecular Biology
Allele frequency
Alleles
Micronuclei
Chromosome-Defective
Aged
Organic Chemistry
Promoter
DNA Methylation
medicine.disease
Molecular biology
digestive system diseases
lcsh:Biology (General)
lcsh:QD1-999
ROC Curve
Case-Control Studies
Cancer research
Septins
Zdroj: International Journal of Molecular Sciences
Volume 16
Issue 12
Pages 28486-28497
International Journal of Molecular Sciences; Volume 16; Issue 12; Pages: 28486-28497
International Journal of Molecular Sciences, Vol 16, Iss 12, Pp 28486-28497 (2015)
ISSN: 1422-0067
Popis: One challenge in colorectal cancer (CRC) is identifying novel biomarkers to be introduced in screening programs. The present study investigated the promoter methylation status of the SEPT9 gene in peripheral blood samples of subjects’ positive fecal occult blood test (FOBT). In order to add new insights, we investigated the association between SEPT9 promoter methylation and micronuclei frequency, and polymorphisms in the folate-related pathway genes. SEPT9 promoter methylation, micronuclei frequency, and genotypes were evaluated on 74 individuals’ FOBT positive. Individuals were subjected to a colonoscopy that provided written informed consent for study participation. SEPT9 promoter methylation status was significantly lower in the CRC group than controls (p = 0.0006). In contrast, the CaCo2 cell-line, analyzed as a tissue specific model of colon adenocarcinoma, showed a significantly higher percentage of SEPT9 promoter methylation compared to the CRC group (p <
0.0001). Linear regression analysis showed an inverse correlation between micronuclei frequency and the decrease in the methylation levels of SEPT9 promoter region among CRC patients (β = −0.926, p = 0.0001). With regard to genotype analysis, we showed the involvement of the DHFR polymorphism (rs70991108) in SEPT9 promoter methylation level in CRC patients only. In particular, the presence of at least one 19 bp del allele significantly correlates with decreased SEPT9 promoter methylation, compared to the 19 bp ins/ins genotype (p = 0.007). While remaining aware of the strengths and limitations of the study, this represents the first evidence of a novel approach for the early detection of CRC, using SEPT9 promoter methylation, micronuclei frequency and genotypes, with the potential to improve CRC risk assessment.
Databáze: OpenAIRE
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