Abstract for presentation at 11th International Congress of Human Genetics

An absulate production of the huamn EGF gene regualtes by NFk-B binding site at position +62

  • Dr Majid Shahbazi, Genetics & immunology Unit, Medical Faculty, Golestan University of Medical Sciences, Gorgan, Iran, Iran
  • Dr Vera Pravica, 3.239 CID , School of life Sciences, Stopford Building, University of Manchester, Manchester M13 9PT, UK, United Kingdom
  • Dr Anthony Fryer, Center for Cell & Molecular Medicine, School of Postgraduate Medicine, Keel University, North Staffordshire Hospital, Stoke-on-, United Kingdom
  • Dr Richard Strange, Center for Cell & Molecular Medicine, School of Postgraduate Medicine, Keel University, North Staffordshire Hospital, Stoke-on-, United Kingdom
  • Dr Peter Hutchinson, Department of Dermatology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK, United Kingdom
  • Dr Joy Osborne, Department of Dermatology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK, United Kingdom
  • Dr John Lear, Department of Dermatology, North Staffordshire Hospital, Stoke-on-Trent, Staffordshire ST4 7PA, UK
  • Prof Ian Hutchinson, 3.239 CID , School of life Sciences, Stopford Building, University of Manchester, Manchester M13 9PT, UK

    • Epidermal growth factor (EGF) has been found to influence the growth and function of many mammalian cells. Human EGF is encoded by a single gene on chromosome 4q25-q27, and compromises 24 exons spanning nearly 120 kb.
    It is very important during embryogenesis and has a variety of biological activities in many different tissues t has been shown that unregulated expression of epidermal growth factor receptor (EGFR) is a common event in neoplastic transformation and is associated with melanocytic tumour progression. Many biological activities have been described for EGF, including mitogenesis, which is especially relevant to wound healing, tumourogenesis and proliferation of epidermal tissues. We have identified a single nucleotide change (G®A) at position +61 from the transcription start site of the EGF gene and established PCR-RFLP analysis for typing purposes. Allele frequencies in 99 individuals were 56% EGF +61*A and 44% EGF +61*G. Levels of EGF production in vitro were associated with the EGF genotype. Cells from A homozygous individuals produced significantly less EGF compared to cells from homozygous G (p=0.003) or heterozygous G/A (p<0.001) individuals. The affect of EGF production with at position +62 confirm by Gel shift and lucifrease assay at Hela and Cos-7 cells
    In this study we observed significant association between EGF genotype and the development of melanoma. By reason of EGF is involved tumourogenesis the polymorphism identified was tested as potential genetic marker for the detected intraindividual differences in melanoma growth in 100 melanoma patients. A highly significant correlation was observed (p<0.0001) between the presence of the *G allele and the development of melanoma Therefore, high EGF production more involved in melanoma development. Interestingly, high producer of EGF also significantly was seen association with Breslow thickness
    We predict that the polymorphism at position +61 will be a useful marker not only for melanoma but can also be used as a genetic marker in a wide range of studies into the physiological and pathological roles of the important multifunctional EGF and lead to the development of new treatment strategies.

    Conference Organiser - ICMS Pty Ltd