DNA methylation in high-grade anal neoplasia

  • Research type

    Research Study

  • Full title

    DNA methylation as a biomarker to detect high grade anal intraepithelial neoplasia (HGAIN)

  • IRAS ID

    132370

  • Contact name

    Mayura Nathan

  • Contact email

    mayura.nathan@homerton.nhs.uk

  • Sponsor organisation

    Homerton University Hospital

  • Research summary

    e incidence of anal cancer has been increasing over the past few decades. Anal cancer has a precancerous stage known as high grade anal intraepithelial neoplasia (HGAIN), and it is possible that early treatment of HGAIN could prevent cancer from developing. However, there is currently no effective screening mechanism to detect HGAIN, and a suitable biomarker is yet to be discovered. Human papilloma virus (HPV) infection is thought to be present in around 90% of anal cancers. Testing for high risk HPV is well established for cervical screening, but is not feasible in anal cancer because almost all individuals who are at high risk of disease have HPV infection. One possibility is looking at DNA methylation (a mechanism used to regulate genes) of high risk HPV types to identify individuals with HGAIN. Our group has shown that DNA methylation of HPV16 can identify the presence of high grade cervical intraepithelial neoplasia (the precursor disease for cervical cancer) and cervical cancer. We plan to study HPV methylation and candidate human gene methylation in anal tissue with various degrees of anal intraepithelial neoplasia (AIN) and anal cancer.

    We will compare HPV (and other candidate genes) DNA methylation in anal tissue from patients with normal histology, AIN1, AIN2, AIN3 and anal carcinoma, to see if DNA methylation is able to distinguish normal tissue from HGAIN and anal carcinoma. We will also evaluate whether HPV DNA methylation is able to predict whether or not HGAIN will go on to develop into cancer. Tissue will be provided anonymously from existing stores of surplus tissue (from men and women aged 18 and above) that has been removed for diagnostic purposes, from Barts Health NHS Trust. Laboratory work will be performed in Professor Lorincz’s lab at Queen Mary University of London.

  • REC name

    London - Camden & Kings Cross Research Ethics Committee

  • REC reference

    13/LO/1519

  • Date of REC Opinion

    20 Sep 2013

  • REC opinion

    Favourable Opinion