Cancer Risk in Carriers of the Gene for Xeroderma Pigmentosum
| Status: | Recruiting |
|---|---|
| Conditions: | Skin Cancer, Cancer, Cancer, Dermatology |
| Therapuetic Areas: | Dermatology / Plastic Surgery, Oncology |
| Healthy: | No |
| Age Range: | Any - 99 |
| Updated: | 2/10/2019 |
| Start Date: | April 7, 2003 |
| Contact: | Kenneth H Kraemer, M.D. |
| Email: | kraemerk@mail.nih.gov |
| Phone: | (240) 760-6139 |
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
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
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.
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.
- 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. 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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: (888) NCI-1937
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