Aberrant p16 promoter hypermethylation in bronchial mucosae as a biomarker for the early detection of lung cancer

摘要

Lung cancer is the leading cause of cancer related death in the world and its mortality could be greatly reduced by diagnosis and treatment in its early stages. Effective tools for the early detection of lung cancer and its high risk factors remain a major challenge. Biomarkers that detect lung cancer in its early stages or identify its pretumour lesions, enabling early therapeutic intervention, would be invaluable to improve its dismal prognosis.DNA methylation plays an essential role in normal development and maintaining genomic stability. Alterations in methylation patterns frequently occur in tumour cells and hypermethylation in the promoter region of tumour suppressor genes, associated with epigenetically mediated gene silencing, is a common feature of human cancers. Previous studies in cancer epigenesis have demonstrated that a number of tumour suppressor genes, such as p16, APC, FIHT, RARβ, MGMT, DAPK, CDH13, RASSFIA, TIMP-3 and GSTP1, are hypermethylated in lung cancer. Aberrant promoter hypermethylation of p16, a well known tumour suppressor gene, has been detected in a variety of malignancies, including lung cancer patients prior to its clinical evidence, and is an early event in lung carcinogenesis and may be used as a biomarker for its early diagnosis. However, few studies have analysed control cases to assess its clinical usefulness.