Abstract
BackgroundAlthough TP53 mutations in human tumours generally have been extensively studied, the significance of p53 in the aetiology of head and neck cancers is still incompletely characterized. In recent years, considerable interest has been focused on mutant forms of p53, the abnormal protein product of TP53 alleles with missense mutation that often accumulate in cancer cells.MethodsWe compared the nature of TP53 mutations in primary 46 head and neck squamous cell carcinomas (HNSCC) analyzed by PCR-SSCP and sequencing, immunohistochemistry, and using structural information available at IARC p53 database.ResultsSequencing confirmed 36 TP53 mutations in 23 tumours of the 39 mutations in 26 tumours found by PCR-SSCP. Only half (17) putatively affect the function of p53 protein. Of these 8 were in the L2 domain, three affected the LSH motif and three the L3 domain. Three were in other domains. Codon 259 (GAC > GAA) which is a very rare mutation was found in 4 samples in our study. There were indications of p53 aberrations being associated with the combined effect of smoking, alcohol and work history. Patients with a negative family history of cancer had more often TP53 mutations than patients with a positive family history (71% vs. 46%).ConclusionsOur study contributes to the knowledge of cumulative chemical exposure and p53 aberrations in head and neck cancer, an area where literature is scarce.
Highlights
Carcinomas of the head and neck are among the most common types of cancer [1] and as such represent a major health problem
The 46 head and neck cancers analyzed in this paper provide a significant addition the data in IARC TP53 mutation database, especially due to the known environmental exposures
Mutations in the TP53 gene in head and neck tumours Judging by singlestrand conformation polymorphism (SSCP) the TP53 gene was mutated in a total of 26 primary tumours (57%) in the 46 head and neck squamous cell carcinomas (HNSCC) patients with altogether 39 TP53 mutations
Summary
Carcinomas of the head and neck are among the most common types of cancer [1] and as such represent a major health problem. It is difficult to distinguish the effects and risks of individual carcinogens from all other exposures, it is clear that head and neck squamous cell carcinoma (HNSCC) is epidemiologically strongly associated with alcohol consumption and exposure to tobacco smoke [2]. Associations between head and neck cancer risk and exposures to other environmental and occupational factors have been proposed [5]. Putative occupational risk factors include nickel refining, woodworking, and exposure to textile fibres. TP53 mutations in human tumours generally have been extensively studied, the significance of p53 in the aetiology of head and neck cancers is still incompletely characterized. Considerable interest has been focused on mutant forms of p53, the abnormal protein product of TP53 alleles with missense mutation that often accumulate in cancer cells
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