Global DNA Methylation Level in Whole Blood as a Biomarker in Head and Neck Squamous Cell Carcinoma
- 1 January 2007
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Epidemiology, Biomarkers & Prevention
- Vol. 16 (1), 108-114
- https://doi.org/10.1158/1055-9965.epi-06-0636
Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is commonly associated with tobacco and alcohol exposures, although dietary factors, particularly folate, and human papillomavirus, are also risk factors. Epigenetic alterations are increasingly implicated in the initiation and progression of cancer. Genome-wide (global) hypomethylation seems to occur in early neoplasia and is a feature of genomic DNA derived from solid tumor tissues, including HNSCC. This study aimed to determine whether global methylation in DNA derived from whole blood, a proxy tissue, is associated with HNSCC and to assess potential modification of this property by environmental or behavioral risk factors. Methods: Global DNA methylation levels were assessed using a modified version of the combined bisulfite restriction analysis of the LRE1 sequence in a population-based case-control study of HNSCC from the Boston area. Results: Hypomethylation lead to a significant 1.6-fold increased risk for disease (95% confidence interval, 1.1-2.4), in models controlled for other HNSCC risk factors. Smoking showed a significant differential effect (P < 0.03) on blood relative methylation between cases and controls. Furthermore, in cases, variant genotype in the MTHFR gene and low folate intake showed relationships with decreased global methylation, whereas in controls, antibody response to human papillomavirus 16 was associated with an increased global methylation level. Discussion: DNA hypomethylation in nontarget tissue was independently associated with HNSCC and had a complex relationship with the known risk factors associated with the genesis of HNSCC. (Cancer Epidemiol Biomarkers Prev 2007;16(1):108–14)Keywords
This publication has 50 references indexed in Scilit:
- The epigenetic progenitor origin of human cancerNature Reviews Genetics, 2006
- Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinomaInternational Journal of Experimental Pathology, 2005
- Epidemiology of head and neck cancer: Magnitude of the problemCancer and Metastasis Reviews, 2005
- Novel markers for poor prognosis in head and neck cancerInternational Journal of Cancer, 2004
- Distinctive pattern of LINE-1 methylation level in normal tissues and the association with carcinogenesisOncogene, 2004
- The history of cancer epigeneticsNature Reviews Cancer, 2004
- DNA methylation in cancer: too much, but also too littleOncogene, 2002
- A bird's eye view of global methylationNature Genetics, 2000
- DNA Methylation in Folate Deficiency: Use of CpG MethylaseBiochemical and Biophysical Research Communications, 1993
- The effect of joint exposure to alcohol and tobacco on risk of cancer of the mouth and pharynxJournal of Chronic Diseases, 1972