Cancer Risk in Carriers of the Gene for Xeroderma Pigmentosum - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00046189

Purpose

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

Study Type:	Observational
Official Title:	Cancer Risk in Xeroderma Pigmentosum Heterozygotes

Resource links provided by NLM:

Genetics Home Reference related topics: lamellar ichthyosis nonbullous congenital ichthyosiform erythroderma xeroderma pigmentosum Help Me Understand Genetics

MedlinePlus related topics: Cancer Skin Cancer

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment:	800
Study Start Date:	September 2002

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 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.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00046189

Contacts

Contact: NCI Referral Office

1-888-NCI-1937

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892
Sub-Investigator: National Cancer Institute Referral Office For more information at the NIH Clinical Center contact

Sponsors and Collaborators

National Cancer Institute (NCI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

[No authors listed] Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility, Adopted on February 20, 1996. J Clin Oncol. 1996 May;14(5):1730-6; discussion 1737-40.

Chen J, Birkholtz GG, Lindblom P, Rubio C, Lindblom A. The role of ataxia-telangiectasia heterozygotes in familial breast cancer. Cancer Res. 1998 Apr 1;58(7):1376-9.

Cheo DL, Meira LB, Burns DK, Reis AM, Issac T, Friedberg EC. Ultraviolet B radiation-induced skin cancer in mice defective in the Xpc, Trp53, and Apex (HAP1) genes: genotype-specific effects on cancer predisposition and pathology of tumors. Cancer Res. 2000 Mar 15;60(6):1580-4.

ClinicalTrials.gov Identifier:	NCT00046189 History of Changes
Obsolete Identifiers:	NCT00049621
Other Study ID Numbers:	020313, 02-C-0313
Study First Received:	September 21, 2002
Last Updated:	February 3, 2012
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

DNA Repair
Molecular Epidemiology
Skin Cancer
Genetics

Melanoma
Xeroderma Pigmentosum
XP

Additional relevant MeSH terms:

Ichthyosis
Xeroderma Pigmentosum
Skin Abnormalities
Congenital Abnormalities
Infant, Newborn, Diseases
Keratosis
Skin Diseases
Precancerous Conditions

Neoplasms
Skin Diseases, Genetic
Genetic Diseases, Inborn
Photosensitivity Disorders
Pigmentation Disorders
DNA Repair-Deficiency Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on February 13, 2012