The purpose of our study was to evaluate the frequency of hypermethylated tumor suppressor genes (TSGs) in peripheral blood, mouth and throat (M&T) rinsing fluid and nasopharyngeal (NP) swabs of nasopharyngeal carcinoma (NPC) patients. Six normal NP tissues, 43 M&T rinsing fluid, 37 NP swabs and 43 peripheral blood from healthy non-smokers and non-drinkers without a family history of NPC, and 30 NPC tumors and their matched body fluid were analyzed for the presence of hypermethylated p15, p16, Ras association domain family 1 (RASSF1A), E-cadherin, and death-associated protein kinase (DAPK) by methylation-specific PCR. Sequencing analysis was carried out on selected NPC tumors and body fluid samples. Twenty-nine (97%) tumors displayed methylation in at least 1 of the 5 genes. The methylation frequencies were 80% for p15, 77% for DAPK, 67% for RASSF1A, 53% for Ecadherin and 33% for p16. The frequency range of aberrant methylated genes in the body fluids were NP swabs (17-63%) and M&T rinsing fluid (17-50%). Methylation was found in <20% of peripheral blood for each respective gene. Methylation was, however, detected in 1 M&T rinsing fluid in which the primary tumor showed methylation free for RASSF1A. Key words: promoter hypermethylation; tumor suppressor gene; nasopharyngeal swab; M & T rinsing fluid; nasopharyngeal carcinomaNasopharyngeal carcinoma (NPC) is classified by WHO into 3 histologic types including the squamous cell carcinoma (Type I), non-keratinizing carcinoma (Type II) and undifferentiated carcinoma (Type III). Undifferentiated carcinoma is more prevalent in southern Chinese and Asians. The development of NPC might be attributable to a complex interaction of genetic factors, dietary exposure to chemical carcinogen and EBV infection. 1 Hypermethylation of CpG-island in promoter region of proven or candidate TSGs has been increasingly implicated as an early event in carcinogenesis. [2][3][4] Although promoter hypermethylation of many of these genes can be found in different histological types of cancers, the patterns of promoter hypermethylation are distinctly different in different cancers. 5 The reported frequencies of promoter methylation in NPC were 84% for RASSF1A, 80% for RARbeta2, 46% for p16, 17% for p15, 20% for p14, 20% for MGMT, and 3% for GSTP1. 6 In our previous study of DAPK, hypermethylation was found in 24 (75%) NPC primary tumors. 7 Our studies suggest promoter hypermethylation of TSGs are commonly found in NPC and play a significant role in the development of NPC.There is no accurate clinical screening method for NPC. Radiological imaging including CT or MRI scan and endoscopic guided nasopharyngeal (NP) biopsy for histological examination are expensive and invasive. These radiologic and surgical procedures are not suitable for screening of NPC, and they cannot be repeated serially in monitoring residual or recurrent tumor after treatment.We have previously done a population screening of 67,891 healthy southern Chinese with EBV serology, it has reasonably high sensitivity but has lo...

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