Global DNA methylation level in whole blood as a biomarker in head and neck squamous cell carcinoma.
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.


CONCLUSIONS
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.
Hsiung
Debra Ting
DT
Department of Genetics and Complex Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
Marsit
Carmen J
CJ
Houseman
E Andres
EA
Eddy
Karen
K
Furniss
C Sloane
CS
McClean
Michael D
MD
Kelsey
Karl T
KT
D000428:Alcohol Drinking; D015415:Biomarkers / Q000097:blood*; D001900:Boston; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking
D015415:Biomarkers