Promoter hypermethylation of tumour suppressor genes in tumour cells from patients with head and neck cancer

Abstract

Head and neck cancer is a group of malignancies of the upper respiratory tract, its main risk factors being attributed to tobacco and alcohol consumption and human papillomavirus (HPV) infection. Promoter hypermethylation is one of the major mechanisms in the transcriptional inactivation of tumour suppressor genes (TSGs) in human cancer. In this study, aberrant methylation in the promoter regions of five TSGs and the prevalence of HPV was analysed in order to evaluate the role of epigenetic changes in head and neck carcinogenesis, and to clarify its causative relation with HPV infection and smoking behaviour. Brushing specimens collected from the tumour or oral mucosa from 38 cases with head and neck cancer and 42 controls were included in the study and tested for HPV infection. 34% of cancer patients and 12% of controls were infected by HPV. Brushings from 31 tumours and 11 control samples were analysed by means of methylation-specific PCR. Hypermethylation of at least one gene was detected in 71% of tumours. Epigenetic changes were more frequent in smokers than in never-smokers (p = 0.047), and in cancer cases hypermethylation was more prevalent in late-stage tumours. The study shows a significant role of epigenetic changes in head and neck carcinogenesis. Analysis of promoter hypermethylation of selected TSGs in oral brushing specimens from high-risk cases can serve as a simple method for early prediction of head and neck cancer risk. Keywords: head and neck cancer, tumour suppressor genes, DNA hypermethylation, HPV