Abstract. Non-melanoma skin cancer (NMSC) is classified among the ten most frequent cancers in Malaysia. A common polymorphism at codon 72 of the p53 tumor suppressor gene and its influence on cancer risk has been studied for different types of cancer with mixed and inconsistent results with limited published data on the Malaysian population so far. In the present study, the frequency of p53 codon 72 polymorphism in 60 patients with NMSC was investigated from archival formalin-fixed paraffin-embedded (FFPE) tissue obtained from Hospital Universiti Kebangsaan Malaysia (HUKM). Additionally, random amplified polymorhic DNA -polymorphic chain reaction (RAPD-PCR) was employed for preliminary biomarker development. NMSC FFPE samples (70%) possess Arg/Arg, 20% with Pro/Pro and 10% with Arg/ Pro. In total, there was no significant difference in the p53 codon 72 genotypes between histological types of NMSC, gender, race, tumor location and age group. However, there was an apparent age-associated increase in the Arg/Arg genotype but did not reach statistical significance (P= 0.235). NMSC types and demographic characteristics did not influence genotype distribution. On the other hand, BCC and SCC distributions are influenced by age group, race and tumor location.
IntroductionNon-melanoma skin cancer (NMSC) is the most common type of cancer among different populations worldwide.Consisting of two histological types i.e. basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), the BCC accounts for 80% and SCC for the rest (1). Regardless of its low clinical aggressiveness, due to its frequency and cost of treatment, it is a heavy public health burden (2). In Malaysia, official statistics rank NMSC among the ten most common types of cancer in adults (3). Exposure to sun is considered the main causative agent for NMSC (4). However, it cannot account for all of NMSC etiology since other physical and chemical agents, such as ionizing radiation, arsenic and coal tar products, as well as suppression of immune system in transplant patients, are verified causes of NMSC (5). Furthermore, genetic polymorphism is proposed to modify the risk of the disease (6).The p53 tumor suppressor protein plays an essential part in maintaining cellular integrity and tissue homeostasis through its ability to orchestrate the transcriptional activation of other genes (7). A critical region of p53 for signaling apoptosis lies between codons 64 and 92, encoding a proline-rich region of the gene homologous to an SH3 binding domain (8-10) in which there is a common polymorphism resulting in either an arginine (CGC) or a proline (CCC) at codon 72 of exon 4. This is a non-conservative amino acid change and results in a structural change in the protein as the p53Pro variant migrates more slowly than the p53Arg variant in sodium dodecyl sulfatepolyacrylamide gel electrophoresis (11). The two alleles of p53 differ biologically. p53Arg induces 5-10 times more apoptosis than p53Pro, which is explained in part by a higher ability of p53Arg to localize to the m...