A novel C/T polymorphism in the core promoter of human de novo cytosine DNA methyltransferase 3B6 is associated with prognosis in head and neck cancer

• Published in: International journal of oncology Vol. 25; no. 4; p. 993
• Main Authors: Wang, Luo, Rodriguez, Marivonne, Kim, Edward S, Xu, Yunling, Bekele, Neby, El-Naggar, Adel K, Hong, Waun Ki, Mao, Li, Oh, Yun W
• Format: Journal Article
• Language: English
• Published: Greece 01.10.2004
• Subjects: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA Methyltransferase 3B; Female; Genotype; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - pathology; Humans; Male; Middle Aged; Polymorphism, Genetic; Prognosis; Promoter Regions, Genetic
• ISSN: 1019-6439

New biomarkers for head and neck squamous cell carcinoma (HNSCC) patients are being sought to help predict disease outcome, guide treatment, and develop new treatments. In the present study, the association between a novel functional C/T polymorphism in the core promoter of cytosine DNA methyltransferase (DNMT) 3B6 and overall survival of HNSCC patients was investigated. Genomic DNA was extracted from tumor tissue and leukocytes from each HNSCC patient. We used the PCR-restriction fragment length polymorphism (PCR-RFLP) assay to determine the DNMT3B genotype. Kaplan-Meier product-limit method and univariate/multivariate Cox proportional hazard models were used to correlate DNMT3B genotype with overall survival of HNSCC patients who underwent surgical resection. There was a marked association between DNMT3B C/T polymorphism and overall survival of HNSCC patients (P=0.004). The homozygotes (CC-genotype and TT-genotype) survived significantly longer than the heterozygotes (CT-type). The multivariate Cox proportional hazard modeling showed that HNSCC patients with CT-genotype had a hazard ratio of 4.829 over patients with CC-genotype or TT-genotype. A DNMT3B C/T polymorphism has been correlated with survival differences in HNSCC patients. If validated in larger studies, this polymorphism might be used to identify deleterious patterns of gene silencing by methylation in HNSCC.