DNA promoter methylation and head and neck cancer survival

B106

Background: An estimated 34,360 new squamous cell carcinoma of the head and neck (SCCHN) cancers and 7,550 deaths will occur in the U.S. in 2007, accounting for 3-5% of all malignancies. About 30-50% of SCCHN patients will develop a recurrence and/or a second primary tumor during the follow up. It is important to define early predictors of cancer recurrence at time of diagnosis.
 >Methods: 89 subjects undergoing surgical resection of their first primary tumors were enrolled, after informed consent, at the University of Pittsburgh; patient demographic, smoking and alcohol use, clinical treatment and follow-up information were collected with a standardized questionnaire. HPV status was known for all the tumors DNA from tumors was extracted, and methylation-specific PCR was used for the analysis of MGMT and CDKN2A promoter methylation.
 >Results: Themean age of thepatients was 62.3 + 12.9 years; 64.0% of them were males. Average follow up was 65.2 + 49.0 months. 30.3% of the tumors showed MGMT promoter methylation and 11.5% showed CDKN2A methylation. MGMT promoter methylation was significantly associated with both recurrence (p=0.03) and overall survival (p=0.02). A non-significant inverse association of promoter hypermethylation and both recurrence and survival was observed for CDKN2A. Only 3.3% of the samples showed hypermethylation of both MGMT and CDKN2A. All of the HPV-positive tumors carried non-methylated CDKN2A promoters. This is likely related to the fact that HPV positive tumors are more likely to over-express p16.
 >Conclusions: MGMT promoter hypermethylation is a predictor of SCCHN outcome, possibly because of its role in apoptotic and DNA repair. Further studies are needed to investigate the interaction between promoter hypermethylation of MGMT, CDKN2A, and HPV infection and their combined effect on SCCHN outcome.