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

Condition
Xeroderma Pigmentosum

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 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.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Members of the XP families where the proband has previously been evaluated at the Clinical Center or is newly diagnosed under other approved protocols (primarily 99-C-0099) are eligible to participate in this study. Families with XP patients of any age, gender or race are eligible for this study.
On referral, families of XP patients will be considered for inclusion in the study if the proband has clinical documentation of features of XP and laboratory determination of the DNA repair defect. All relatives of XP patients including spouses are eligible to participate.
EXCLUSION CRITERIA:
Inability or unwillingness to provide family history information or tissue (skin, blood, buccal cells or hair) for laboratory studies.

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  020313; 02-C-0313
Record last reviewed:  August 19, 2004
Last Updated:  August 19, 2004
Record first received:  September 21, 2002
ClinicalTrials.gov Identifier:  NCT00046189
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-29