Hereditary NeoplasmsNCT00001163
Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Cancer
An observational study of Hereditary Neoplasms and Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This is a clinical, epidemiologic, genetic, and laboratory study of individuals and families at high risk of cancer and selected tumors to investigate the genetic susceptibility and environmental exposures which may alter cancer risk. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hereditary Neoplasms, Cancer, Genetic Predisposition to Cancer
- How many people
- 5,201 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Apr 1985to not given
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Primary clinical; volunteers come from all U.S.
Who may be able to join
- On referral, persons of any age will be considered for the inclusion in the study because of either:
- A family or personal history of neoplasia of an unusual type, pattern, or number; OR,
- known or suspected factor(s) predisposing to neoplasia, either genetic and/or congenital factors (birth defects, metabolic phenotype, chromosomal anomalies or Mendelian traits associated with tumors), environmental exposure (medications, occupation, radiation, diet, infectious agents, etc.), or unusual demographic features (very young age of onset, multiple tumors, etc.).
- Personal and family medical history must be verified through questionnaires, interviews, and review of pathology slides and medical records. For familial neoplasms, two or more living affected cases among family members are required. The types of familial tumors that we are currently actively accruing include:
- Familial Cancers: bladder, brain, chordoma, lung, nevoid basal cell carcinoma syndrome (NBCC)
- Familial Benign Neoplasms: meningiomas, neurofibromatosis 2 (bilateral acoustic neurofibromatosis)
- The types of familial tumors under active accrual and study are predominantly investigator-and hypothesis-driven. This approach permits GEB investigators to remain alert to the opportunities afforded by clusters of rare tumors in families and individuals, and to be more responsive to the dynamic research priorities in cancer genetics.
Who cannot join
- Referred individuals and families for whom reported diagnoses cannot be verified.
- Inability to provide informed consent.
- Eligible for familial melanoma, lymphoproliferative, breast-ovarian cancer, or testicular cancer protocols.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
This is a clinical, epidemiologic, genetic, and laboratory study of individuals and families at high risk of cancer and selected tumors to investigate the genetic susceptibility and environmental exposures which may alter cancer risk. Families with multiple members who have an unusual pattern or number of cancers or tumors are evaluated clinically. This evaluation is specific for the type of cancer or tumor predominant in the family in order to determine the affection status of each individual for genetic epidemiologic studies. Genetic and environmental risk factor information specific for the tumor type is obtained.
Individuals with, or at high risk of, cancer because of their personal, familial, or environmental histories are identified by healthcare worker referral or by personal inquiry. Relevant etiologic risk factor information is documented through review of pathology specimens and medical, vital, and genealogical records. Selected individuals and family members are asked to complete questionnaires and to undergo clinical evaluations specific for the tumor of interest. They are also asked to donate biologic specimens to be used in the search for cancer etiology and mechanisms of carcinogenesis. No therapy beyond counseling and education for cancer prevention, risk reduction, and early detection will be given.
Read more
Genetic testing for tumor susceptibility gene(s) mutations and risk notification will be offered to study participants for whom a specific mutation predictive of disease has been identified in his/her family. This testing will only be offered when reasonable individual cancer risk estimates can be delivered, and only to those participants who choose to know their individual genetic status after appropriate education and counseling. The testing will be conducted exclusively in Clinical Laboratory Improvement Amendments (CLIA)-licensed laboratories. Genetic testing and risk notification are entirely optional and do not affect participation in other aspects of the protocol. A separate consent procedure and consent form will be used for genetic testing and risk notification related to these specific genes.
Once enrolled, study participants are monitored prospectively for the development of outcomes of interest, typically by means of periodic mail or telephone contact. In selected instances, subjects may return to the Clinical Center periodically for study-specific follow-up examinations. Although we do not offer specific anti-cancer therapy as part of this protocol, we provide assistance to insure that study participants who require treatment for tumor-related problems that develop during the course of the study are referred to appropriate healthcare providers. We remain available to study participants and their healthcare providers for advice and consultation related to the management of familial cancer/tumor predisposition.
Read the detailed description
Background:
Persons may be prone to develop cancer for a variety of reasons including: inherited predisposition benign, premalignant, or malignant conditions; environmental exposures shared by family members; previous tumors, immune deficiency, or preneoplastic conditions.
Investigations of individuals and families at high risk of cancer often lead to etiologic clues that may be important in the sporadic counterparts of these cancers in the general population.
Identification of etiologically important genetic factors could inform chemoprevention trials, screening programs, and treatment of the studied cancer types.
Objectives:
To evaluate and define the clinical spectrum and natural history of disease in syndromes predisposing to cancer.
To evaluate potential precursor states of disease in families at risk.
To quantify risks of tumors in family members.
To map, clone, and determine function of tumor susceptibility genes.
To identify genetic determinants, environmental factors, and gene-environment interactions conferring cancer risk in individuals and families.
To evaluate gene-gene and gene-environment interactions in tumor formation.
To educate and counsel study participants about their tumor risk including prevention recommendations and early detection activities when known.
To develop educational materials for medical professionals and high-risk family members.
Eligibility:
Persons of any age will be considered for inclusion in the study because of either,
A family or personal medical history of neoplasia of an unusual type, pattern, or number; or,
Known or suspected factor(s) predisposing to neoplasia, either genetic and/or congenital factors, environmental exposure, or unusual demographic features.
Types of familial tumors that we are currently actively accruing include Cancers: bladder, bone, brain, chordoma, lung, nevoid basal cell carcinoma syndrome (NBCC).
Design:
This is a prospective study. Individuals and families are studied long-term, using a cohort approach.
The study design and clinical evaluation vary by the specific type of familial neoplasm being studied.
The overall approach to eligible study participants includes defining affection status, characterization of disease, localization of genetic loci, identification of genes, evaluation of phenotype/genotype correlations, estimation of risk of the disease associated with carrier status and identification of other risk factors that modify penetrance (genetic, environmental, host factors).
- Keywords
- Cancer, Genes/Genetics, Hereditary Neoplasms, Environment, Natural History
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | primary clinical; volunteers come from all U.S. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Defining the natural history of familial cancers and susceptibility states over multiple generations, identifying cancer susceptibility genes, and assessing gene-environment and gene-gene interactions
New cancer development or current health status
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start2 Apr 1985
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hereditary NeoplasmsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Other
- Enrolment
- 5,201 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sharon A Savage, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001163
- Sponsor's protocol ID
- 780039
- Other IDs
- 78-C-0039
- Status last verified
- 11 Jun 2026
- First submitted
- 3 Nov 1999
- Last updated
- 22 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Section 6.2 titled Data Sharing Plan in the protocol describes the plan for data sharing plans including human data sharing and genomic data sharing plan.@@@@@@Genotype and sequence data along with clinical phenotypes will be deposited in a genomic database in accordance with current NIH Genomic Data Sharing (GDS) Policy and the NIH Human Data Sharing Policy.@@@@@@The following human data generated in this research will be shared for future research as follows:@@@De-identified data in an NIH-funded or approved public repository.@@@@@@De-identified data in BTRIS (automatic for activities in the Clinical Center)@@@@@@De-identified or identified data with approved outside collaborators under appropriate agreements.@@@@@@The data will be shared at the time of publication or shortly after.@@@@@@Unlinked genomic data will be deposited in public genomic databases such as dbGaP in compliance with the NIH Genomic Data Sharing Policy.
Publications
Pathak A, Seipel K, Pemov A, Dewan R, Brown C, Ravichandran S, Luke BT, Malasky M, Suman S, Yeager M; NCI DCEG Cancer Genomics Research Laboratory; NCI DCEG Cancer Sequencing Working Group; Gatti RA, Caporaso NE, Mulvihill JJ, Goldin LR, Pabst T, McMaster ML, Stewart DR. Whole exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow up of a large family. Haematologica. 2016 Jul;101(7):846-52. doi: 10.3324/haematol.2015.130799. Epub 2015 Dec 31.
PubMed 26721895Pathak A, Pemov A, McMaster ML, Dewan R, Ravichandran S, Pak E, Dutra A, Lee HJ, Vogt A, Zhang X, Yeager M, Anderson S, Kirby M; NCI DCEG Cancer Genomics Research Laboratory; NCI DCEG Cancer Sequencing Working Group; Caporaso N, Greene MH, Goldin LR, Stewart DR. Juvenile myelomonocytic leukemia due to a germline CBL Y371C mutation: 35-year follow-up of a large family. Hum Genet. 2015 Jul;134(7):775-87. doi: 10.1007/s00439-015-1550-9. Epub 2015 May 5.
PubMed 25939664Korde LA, Mueller CM, Loud JT, Struewing JP, Nichols K, Greene MH, Mai PL. No evidence of excess breast cancer risk among mutation-negative women from BRCA mutation-positive families. Breast Cancer Res Treat. 2011 Jan;125(1):169-73. doi: 10.1007/s10549-010-0923-y. Epub 2010 May 11.
PubMed 20458532Koehly LM, Peters JA, Kenen R, Hoskins LM, Ersig AL, Kuhn NR, Loud JT, Greene MH. Characteristics of health information gatherers, disseminators, and blockers within families at risk of hereditary cancer: implications for family health communication interventions. Am J Public Health. 2009 Dec;99(12):2203-9. doi: 10.2105/AJPH.2008.154096. Epub 2009 Oct 15.
PubMed 19833996
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical, Laboratory, and Epidemiologic Characterization of Individuals and Families at High Risk of Cancer
- ClinicalTrials.gov ID
- NCT00001163
- Acronym / sponsor ID
- 780039
- Keywords
- Cancer, Genes/Genetics, Hereditary Neoplasms, Environment, Natural History
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 5,201 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 2 Apr 1985 (actual)
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a clinical, epidemiologic, genetic, and laboratory study of individuals and families at high risk of cancer and selected tumors to investigate the genetic susceptibility and environmental exposures which may alter cancer risk. Families with multiple members who have an unusual pattern or number of cancers or tumors are evaluated clinically. This evaluation is specific for the type of cancer or tumor predominant in the family in order to determine the affection status of each individual for genetic epidemiologic studies. Genetic and environmental risk factor information specific for the tumor type is obtained.
Individuals with, or at high risk of, cancer because of their personal, familial, or environmental histories are identified by healthcare worker referral or by personal inquiry. Relevant etiologic risk factor information is documented through review of pathology specimens and medical, vital, and genealogical records. Selected individuals and family members are asked to complete questionnaires and to undergo clinical evaluations specific for the tumor of interest. They are also asked to donate biologic specimens to be used in the search for cancer etiology and mechanisms of carcinogenesis. No therapy beyond counseling and education for cancer prevention, risk reduction, and early detection will be given.
Genetic testing for tumor susceptibility gene(s) mutations and risk notification will be offered to study participants for whom a specific mutation predictive of disease has been identified in his/her family. This testing will only be offered when reasonable individual cancer risk estimates can be delivered, and only to those participants who choose to know their individual genetic status after appropriate education and counseling. The testing will be conducted exclusively in Clinical Laboratory Improvement Amendments (CLIA)-licensed laboratories. Genetic testing and risk notification are entirely optional and do not affect participation in other aspects of the protocol. A separate consent procedure and consent form will be used for genetic testing and risk notification related to these specific genes.
Once enrolled, study participants are monitored prospectively for the development of outcomes of interest, typically by means of periodic mail or telephone contact. In selected instances, subjects may return to the Clinical Center periodically for study-specific follow-up examinations. Although we do not offer specific anti-cancer therapy as part of this protocol, we provide assistance to insure that study participants who require treatment for tumor-related problems that develop during the course of the study are referred to appropriate healthcare providers. We remain available to study participants and their healthcare providers for advice and consultation related to the management of familial cancer/tumor predisposition.
Detailed description
Background:
Persons may be prone to develop cancer for a variety of reasons including: inherited predisposition benign, premalignant, or malignant conditions; environmental exposures shared by family members; previous tumors, immune deficiency, or preneoplastic conditions.
Investigations of individuals and families at high risk of cancer often lead to etiologic clues that may be important in the sporadic counterparts of these cancers in the general population.
Identification of etiologically important genetic factors could inform chemoprevention trials, screening programs, and treatment of the studied cancer types.
Objectives:
To evaluate and define the clinical spectrum and natural history of disease in syndromes predisposing to cancer.
To evaluate potential precursor states of disease in families at risk.
To quantify risks of tumors in family members.
To map, clone, and determine function of tumor susceptibility genes.
To identify genetic determinants, environmental factors, and gene-environment interactions conferring cancer risk in individuals and families.
To evaluate gene-gene and gene-environment interactions in tumor formation.
To educate and counsel study participants about their tumor risk including prevention recommendations and early detection activities when known.
To develop educational materials for medical professionals and high-risk family members.
Eligibility:
Persons of any age will be considered for inclusion in the study because of either,
A family or personal medical history of neoplasia of an unusual type, pattern, or number; or,
Known or suspected factor(s) predisposing to neoplasia, either genetic and/or congenital factors, environmental exposure, or unusual demographic features.
Types of familial tumors that we are currently actively accruing include Cancers: bladder, bone, brain, chordoma, lung, nevoid basal cell carcinoma syndrome (NBCC).
Design:
This is a prospective study. Individuals and families are studied long-term, using a cohort approach.
The study design and clinical evaluation vary by the specific type of familial neoplasm being studied.
The overall approach to eligible study participants includes defining affection status, characterization of disease, localization of genetic loci, identification of genes, evaluation of phenotype/genotype correlations, estimation of risk of the disease associated with carrier status and identification of other risk factors that modify penetrance (genetic, environmental, host factors).
Study design
- Observational model
- Family based
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –primary clinical; volunteers come from all U.S. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Primary clinical; volunteers come from all U.S.
Key inclusion criteria (7 listed)
- On referral, persons of any age will be considered for the inclusion in the study because of either:
- A family or personal history of neoplasia of an unusual type, pattern, or number; OR,
- known or suspected factor(s) predisposing to neoplasia, either genetic and/or congenital factors (birth defects, metabolic phenotype, chromosomal anomalies or Mendelian traits associated with tumors), environmental exposure (medications, occupation, radiation, diet, infectious agents, etc.), or unusual demographic features (very young age of onset, multiple tumors, etc.).
- Personal and family medical history must be verified through questionnaires, interviews, and review of pathology slides and medical records. For familial neoplasms, two or more living affected cases among family members are required. The types of familial tumors that we are currently actively accruing include:
- Familial Cancers: bladder, brain, chordoma, lung, nevoid basal cell carcinoma syndrome (NBCC)
Key exclusion criteria (3 listed)
- Referred individuals and families for whom reported diagnoses cannot be verified.
- Inability to provide informed consent.
- Eligible for familial melanoma, lymphoproliferative, breast-ovarian cancer, or testicular cancer protocols.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Defining the natural history of familial cancers and susceptibility states over multiple generations, identifying cancer susceptibility genes, and assessing gene-environment and gene-gene interactions
Time frame: Ongoing
New cancer development or current health status
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
- Background: PubMed 26721895Pathak A, Seipel K, Pemov A, Dewan R, Brown C, Ravichandran S, Luke BT, Malasky M, Suman S, Yeager M; NCI DCEG Cancer Genomics Research Laboratory; NCI DCEG Cancer Sequencing Working Group; Gatti RA, Caporaso NE, Mulvihill JJ, Goldin LR, Pabst T, McMaster ML, Stewart DR. Whole exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow up of a large family. Haematologica. 2016 Jul;101(7):846-52. doi: 10.3324/haematol.2015.130799. Epub 2015 Dec 31.
- Background: PubMed 25939664Pathak A, Pemov A, McMaster ML, Dewan R, Ravichandran S, Pak E, Dutra A, Lee HJ, Vogt A, Zhang X, Yeager M, Anderson S, Kirby M; NCI DCEG Cancer Genomics Research Laboratory; NCI DCEG Cancer Sequencing Working Group; Caporaso N, Greene MH, Goldin LR, Stewart DR. Juvenile myelomonocytic leukemia due to a germline CBL Y371C mutation: 35-year follow-up of a large family. Hum Genet. 2015 Jul;134(7):775-87. doi: 10.1007/s00439-015-1550-9. Epub 2015 May 5.
- Derived from this study: PubMed 20458532Korde LA, Mueller CM, Loud JT, Struewing JP, Nichols K, Greene MH, Mai PL. No evidence of excess breast cancer risk among mutation-negative women from BRCA mutation-positive families. Breast Cancer Res Treat. 2011 Jan;125(1):169-73. doi: 10.1007/s10549-010-0923-y. Epub 2010 May 11.
- Derived from this study: PubMed 19833996Koehly LM, Peters JA, Kenen R, Hoskins LM, Ersig AL, Kuhn NR, Loud JT, Greene MH. Characteristics of health information gatherers, disseminators, and blockers within families at risk of hereditary cancer: implications for family health communication interventions. Am J Public Health. 2009 Dec;99(12):2203-9. doi: 10.2105/AJPH.2008.154096. Epub 2009 Oct 15.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Section 6.2 titled Data Sharing Plan in the protocol describes the plan for data sharing plans including human data sharing and genomic data sharing plan.@@@@@@Genotype and sequence data along with clinical phenotypes will be deposited in a genomic database in accordance with current NIH Genomic Data Sharing (GDS) Policy and the NIH Human Data Sharing Policy.@@@@@@The following human data generated in this research will be shared for future research as follows:@@@De-identified data in an NIH-funded or approved public repository.@@@@@@De-identified data in BTRIS (automatic for activities in the Clinical Center)@@@@@@De-identified or identified data with approved outside collaborators under appropriate agreements.@@@@@@The data will be shared at the time of publication or shortly after.@@@@@@Unlinked genomic data will be deposited in public genomic databases such as dbGaP in compliance with the NIH Genomic Data Sharing Policy.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sharon A Savage, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hereditary Neoplasms and Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Defining the natural history of familial cancers and susceptibility states over multiple generations, identifying cancer susceptibility genes, and assessing gene-environment and gene-gene interactions (time frame: Ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001163, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.