Cancer Risk in Carriers of the Gene for Xeroderma Pigmentosum
Condition: Xeroderma Pigmentosum; Basal Cell Carcinoma; Squamous Cell Carcinoma; Melanoma; Skin Cancer
MeSH terms: Carcinoma; Carcinoma, Basal Cell; Skin Neoplasms; Xeroderma Pigmentosum; Ichthyosis
Study type: Observational

Summary: 
      This study will determine if family members of patients with xeroderma pigmentosum (XP) have
      various abnormalities, including: skin abnormalities; nervous system abnormalities, such as
      hearing problems; skin, eye, or internal cancers, or other changes. XP is a rare inherited
      disease that involves an inability to repair damage to cell DNA (genetic material). It can
      affect several organ systems, including the skin, eye, nervous system, and bones. Patients
      have a more than thousand-fold increase in frequency in all major skin cancers.

      Parents of patients with XP are carriers of the abnormal XP gene. Other family members may
      also be carriers of the abnormal XP gene. Carriers do not develop the disease themselves;
      symptoms develop only in children who have inherited the faulty gene from both parents. This
      study will try to clarify the genetic basis for XP and to understand the increased frequency
      of cancer in the disease.

      XP patients who have been evaluated at the NIH Clinical Center and their relatives are
      eligible for this study. Newly diagnosed XP patients are also eligible. Spouses of relatives
      will also be included as control subjects.

      Patients and their family members will undergo some or all of the following procedures:

        -  Parental permission to review the child s relevant medical records and pathology
           material from treatments or surgery for cancer or other related illnesses

        -  Medical history and physical examination, with particular attention to the skin and
           possible eye, hearing or neurological examinations

        -  Photographs to document skin and other physical findings

        -  Nuclear medicine scans to evaluate the brain and nervous system

        -  X-rays of the skull or other parts of the body

        -  Nervous system testing with an electroencephalogram (EEG), electroretinogram (ERG),
           electromyogram (EMG) or nerve conduction velocity measurement

        -  Collection of blood and skin samples for gene studies

        -  Establishment of cell lines from collected blood or tissues to study DNA repair, skin
           cancer, cancers related to XP, immune defects, and related studies.

        -  Biopsy (surgical removal of a small piece of tissue) of suspicious skin lesions for
           examination under a microscope

        -  Collection of a cheek cell sample, obtained by twirling a soft brush against the inside
           of the cheek

        -  Collection of a hair sample for microscopic examination and composition analysis

        -  Surgery to treat skin cancers or other lesions
    

Detailed description: 
      Xeroderma Pigmentosum (XP) is a rare, recessive disorder with a more than 1000-fold increase
      in the frequency of all major skin cancers in association with defective DNA repair. The risk
      of skin and other cancers among normal appearing XP heterozygote individuals has not been
      fully studied. We plan to study the family members from XP families with known DNA repair
      gene mutations to determine if heterozygote carriers of XP disease mutations are at an
      increased risk of developing cancer. For controls we will compare XP heterozygotes to their
      non-carrier blood relatives and spouses and to the Surveillance, Epidemiology and End Results
      (SEER) rates. For this purpose, blood, skin or buccal cells will be obtained from all
      available relatives for DNA or RNA mutation analysis. Cancer confirmation will be
      accomplished through review of pathology reports, medical records and death certificates. In
      addition, willing family members will be clinically examined to determine current cancer
      status. Individuals who are determined to be heterozygous carriers of XP DNA repair gene
      disease mutations in these families by mutation analysis or by pedigree will be compared to
      non-carrier relatives and spouses with respect to history of any type of cancer. We will also
      focus on skin cancer and cancer of the nervous system since the risks of these cancers are
      elevated among the XP homozygotes.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with XP families where the proband has previously been evaluated at the Clinical
        Center or is newly diagnosed
      
Keywords: Sun Exposure; Xeroderma Pigmentosum; Skin Cancer; Family History; HETEROZYGOTE; Natural History; XP