home
RRP ISA Survey Results


    "Genetics of Papilloma-induced Voice Disturbance" Report

    by Farrel Buchinsky, MD
    February 8, 2007
    We all know that RRP is caused by HPV 6 or 11, and in rare cases 16. Yet many millions of people are exposed to the two viruses and they do not get RRP. So then what is it about the thousands of people with RRP, that their exposure turns into a disease? Furthermore, why do some people just have a “little brush” with RRP while other suffer a crushingly aggressive course? My colleagues and I at the Center for Genomic Sciences at the Allegheny Singer Research Institute in Pittsburgh looked at the available evidence and decided that there must be a genetic susceptibility to the disease.

    www.ncbi.nlm.nih.gov/entrez/query.fcgi

    The Center for Genomic Sciences had state-of-the-art genetic analysis capabilities and the RRP Task Force had access to many patients. Thus a collaboration was formed to enroll patients and their parents to determine the genetic factors that make one susceptible to RRP.

    In 2003 the National Institute on Deafness and Other Communication Disorders (NIDCD) funded the study. Slowly but surely the number of trios (patient + mother + father) grew albeit not as quickly as was needed. Then in 2005 the International RRP ISA sponsored a temporary worker to specifically help would-be Task Force collaborators obtain regulatory approval from their institutions. Obtaining a separate institutional authorization at each and every hospital has been the biggest impediment to enrollment.

    www.ncbi.nlm.nih.gov/entrez/query.fcgi

    Thanks to the support of the ISA, approval was received at additional hospitals and has now reached at total of 19 institutions across the Americas.

    Institutions with IRB Approval
    (ordered by date of authorization)
    Allegheny General Hospital, Pittsburgh
    Children's Hospital of the King's Daughters , Norfolk
    Children's Hospital of Wisconsin, Milwaukee
    Children's National Medical Center, Washington
    Cincinnati Children's Hospital Medical Center , Cincinnati
    Johns Hopkins Children's Center, Baltimore
    Children's Medical Center of Dallas, Dallas
    Children's Hospital of Philadelphia, Philadelphia
    SUNY Upstate Medical Center, Syracuse
    The Hospital for Sick Children, Toronto
    Children's Hospital of Alabama, Birmingham
    University of California - San Francisco, San Francisco
    Children's Hospital of Pittsburgh, Pittsburgh
    Le Bonheur Children's Medical Center, Memphis
    Children's Healthcare of Atlanta at Egleston, Atlanta
    Bastian Voice Institute, Downers Grove
    University of Mississippi Medical Center, Jackson
    British Columbia's Children's Hospital, Vancouver
    Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo

    Also in 2005 we obtained approval to recruit patients and their parents directly through the support groups. Direct enrollment was made possible by advances in technology that enabled us to obtain enough DNA from someone swishing mouthwash, spitting it into a tube and mailing it to our center. Previously we had to rely on blood draws since the more convenient methods yielded too little DNA to work with at that time. The enrollment rapidly rose. As of November 2006, over 500 people have participated in the study with 202 of those people either having RRP currently or at some time in the past. The other 300 people are parents (and some siblings) of the 193 people with RRP.

    The first gene that was investigated was, EVER1 which had been shown to be mutated in a skin disease called Epidermodysplasia Verruciformis (EV). While the rare skin condition is not caused by HPV 6 and 11, it is caused by an unusual susceptibility to HPV 5 and 8. We looked at the DNA of all the patients we had at the time (+35 from Drs Steinberg and Abramson) to see if any of them had the mutations that were described for the skin disease. Not one person had the mutation. We concluded that the mutations causing EV was not the cause of susceptibility to RRP.

    www.ncbi.nlm.nih.gov/entrez/query.fcgi

    We looked at other aspects of the EVER1 gene apart from the described mutations but found no convincing answers. There are many other genes that we want to explore since we know that the proteins they encode have something to do with the way HPV lives in human cells. However, our focus is on a genome-wide approach. We have already analyzed the first few people on a chip that looks at 6000 different spots in the human genome (collection of all of one’s genetic code). The field of genetic discovery is rapidly advancing. It is now possible to look at not just 6000 spots at a time but to analyze 100,000 or 300,000 or even 500,000 of the 3 billion spots that exist in the human genome. Getting so much information from each person will greatly speed up the process and increases chances of discovering the underlying genetic susceptibility. Statistical techniques have been developed that help us make sense of the overwhelming amount of data. One thing is clear though; in order to take advantage of the science and technology the number of enrollees needs to increase a lot (about double) and must do so in the near future. We need to make the most of the opportunity that the NIDCD has afforded. An understanding of this disease will not only satisfy our curiosity but will hopefully lead to better management and possibly a cure.

    A big “Thank You” is due to the 500 people who have participated so far and another big “Thank You” to the International RRP ISA for having sponsored a temporary worker to help with the regulatory approval.

    For more information please visit www.rrpgenetics.org or e-mail info@rrpgenetics.org or call the Center for Genomic Sciences at (888) 887-7729 and from outside the United States call + 1 (412) 359-4707. You may also Skype me (fjbuch) or contact me on Google Talk (fjbuch@gmail.com).

    Farrel J. Buchinsky, MD FACS
    Director, Recurrent Respiratory Papillomatosis Program
    Center for Genomic Sciences
    Allegheny-Singer Research Institute
    320 E. North Avenue
    Pittsburgh, PA 15212
    United States of America
    reply to this post