Cancer Risk in Carriers of the Gene for Xeroderma Pigmentosum

January 5, 2024 updated by: National Cancer Institute (NCI)

Cancer Risk in Xeroderma Pigmentosum Heterozygotes

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

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

301

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Deborah E Tamura, R.N.
  • Phone Number: (240) 760-7355
  • Email: dt220a@nih.gov

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 99 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

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

Description

  • 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 (excluding neonates), gender or race are eligible for this study.

  • On referral, patients with XP and 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. A spouse of a blood relative of a patient with xeroderma pigmentosum would also be eligible.
  • Ability of patient or Legally Authorized Representative (LAR) to sign a written informed consent document

EXCLUSION CRITERIA:

-Inability or unwillingness to provide family history information or tissue (skin, blood, buccal cells or hair) for laboratory studies.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
1
Patients with XP
2
Family members from XP families with known DNA repair gene mutations

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine increased risk of developing cancer
Time Frame: Annual
risk of any type of cancer, skin cancer and cancers of the nervous system are compared in the relatives who are heterozygotes for the XP mutations and relatives who do not carry the XP mutations by calculating the odds ratios
Annual

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Kenneth H Kraemer, M.D., National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 7, 2003

Primary Completion (Actual)

January 5, 2024

Study Completion (Actual)

January 5, 2024

Study Registration Dates

First Submitted

September 21, 2002

First Submitted That Met QC Criteria

September 21, 2002

First Posted (Estimated)

September 23, 2002

Study Record Updates

Last Update Posted (Estimated)

January 8, 2024

Last Update Submitted That Met QC Criteria

January 5, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 020313
  • 02-C-0313

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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