title: Genetic and expressional variations of APEX1 are associated with increased risk of head and neck cancer.
abstract: The aetiology of head and neck cancer (HNC) has been shown to be associated with genetic and certain environmental factors that produce DNA damage. Base excision repair (BER) genes are responsible for repair of DNA damage caused by reactive oxygen species and other electrophiles and therefore are good candidate susceptibility genes for HNC. Apurinic/apyrimidinic endonuclease-1 (APEX1) proteins have important functions in the BER pathway. In this case-control study, all exons of the    APEX1    gene and its exon/intron boundaries were amplified in 300 HNC cases and 300 matched healthy controls and then analysed by single-stranded conformational polymorphism. Amplified products showing altered mobility patterns were sequenced and analysed. To confirm our observations, we examined    APEX1    expression at mRNA level on 50 head and neck squamous cell carcinoma (HNSCC) and 50 normal control samples by quantitative real-time polymerase chain reaction. At germ line level, three novel mutations (13T > G, Ser129Arg and Val131Gly) of APEX1 were observed. The homozygous and heterozygous genotypes of APEX1 13T > G, Ser129Arg and Val131Gly appear to be significantly involved in the development of HNC. In the case of expressional level,    APEX1    mRNA expression was positively correlated with tumour size, clinical stage and positive lymph node metastasis. Statistical analysis showed a significantly higher    APEX1    mRNA level in HNC tumour tissue than in control samples. Our study demonstrated that    APEX1    mutations and deregulation of    APEX1    are associated with increased risk of HNC in the Pakistani population.
authors: Cancer Genetics Lab, Department of Biosciences, COMSATS Institute of Information Technology, Park Road Chak shazad, Islamabad, Pakistan.
authors: Ishrat
authors: I
authors: Mahjabeen
authors: Ruqia Mehmood
authors: RM
authors: Baig
authors: Maimoona
authors: M
authors: Sabir
authors: Mahmood Akhtar
authors: MA
authors: Kayani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004249:DNA Damage; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D059647:Gene-Environment Interaction; D005819:Genetic Markers; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010154:Pakistan; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D005819:Genetic Markers; D012333:RNA, Messenger; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase