Testicular CancerNCT00034424
Cause of Familial Testicular Cancer
An observational study of Testicular Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: People with a family history of testicular cancer may be at increased risk for the disease. Genetic and clinical studies of patients with testicular cancer and their family members may help clarify the cause of the disease and identify clinical features. Read more about this study
- Who is it for?
- Ages 12 to 77 years
- Conditions the study is for
- Testicular Cancer
- How many people
- 749 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jan 2003to not given
- Phase
- Observational
- Are there results?
- None posted in the registry
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 12 to 77 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: A non-randomized cohort study of individuals from families with a significant history of testicular cancer.
Who may be able to join
- Study population:
- Patients must be members of families with familial TGCT as defined below.
- Definition of familial TGCT:
- The criterion establishing familial TGCT is the presence of:
- -at least two cases of documented GCT in blood relatives (at least one of which is testicular in origin),
- OR
Show all 21Show fewer
- a single family member with bilateral testicular cancer,
- men with a history of TGCT who are one in a set of identical siblings will also be included in the study.
- Case definition:
- A case will be determined to have TGCT according to the following criteria:
- Pathologic confirmation of a germ cell derived tumor arising in the testis. Extragonadal germ cell tumors will also be included.
- Germ cell derived histologies including: seminoma, germinoma, embryonal carcinoma, endodermal sinus (yolk sac) tumor, gonadoblastoma, choriocarcinoma, teratoma, and mixed germ cell tumor.
- A case will be determined to have TIN on the basis of pathologic confirmation of intratubular malignant germ cells (ITMGCs) as defined by Burke and Mostofi.
- Individuals from participating families who are eligible for this study include:
- all TGCT cases;
- all GCT cases (including those of ovarian or extra-gonadal sites);
- all first-degree relatives of each GCT case;
- the spouse(s) of every case if the spouse and case had children who are participating in the study;
- any blood relative not included in (ii - iii) above who genetically links two cases; and
- any blood relative with cancer other than GCT
- family members as described in i) - v) above must be age 12 or greater in order to participate
Who cannot join
- Families will be deemed ineligible for participation in this study if:
- There are not at least two confirmed cases of GCT in the family, (at least one of which is testicular in origin), unless there is a family member with bilateral testicular cancer;
- Deceased TGCT cases lacking both archival sources of tissue for DNA extraction AND lacking surviving spouses and children who are willing to participate in the study (the unavailability of such persons prohibits inferring the genotype of the deceased individual with TGCT);
- Critical informative family members are unwilling to participate (i.e., unwilling to provide written informed consent);
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Multidisciplinary Etiologic Study of Familial Testicular Cancer
Background:
People with a family history of testicular cancer may be at increased risk for the disease.
Read more
Genetic and clinical studies of patients with testicular cancer and their family members may help clarify the cause of the disease and identify clinical features.
Objectives:
To characterize the clinical features of testicular cancer.
To identify genes that may lead to increased risk of the disease.
To examine emotional and behavioral issues of members of families at increased risk of the disease.
Eligibility:
Males and females from a family with at least two cases of testicular cancer in blood relatives.
Males with testicular cancer in both testicles.
Males with testicular cancer who have an identical twin.
Participants must be at least 12 years of age.
Design:
Participants may take part in Part 1 or Parts 1 and 2 of this 2-part study.
Part 1 participants:
- Provide a blood or cheek cell sample to obtain DNA for gene studies.
- Provide permission for researchers to obtain their medical records for review.
- Complete questionnaires about their personal and family medical history, exposure to factors that might influence the risk of testicular cancer, and their feelings about being a member of a family in which several members have testicular cancer.
- These data are collected from participants in their home communities.
Part 2 participants:
- All participants provide a medical history, have a complete physical examination, including routine lab tests, and have an ultrasound test of the abdomen to look at the kidneys.
- Males have an ultrasound test of the testicles and scrotum.
- Females have an ultrasound test of the pelvis to look at the ovaries, uterus and fallopian tubes.
- Males 18 years of age and older provide a semen sample.
- Some participants have computed tomography (CT) scanning of the chest, abdomen and pelvis instead of kidney ultrasound. Children under 18 years of age may have magnetic resonance imaging (MRI) instead of CT.
- These data are collected from participants during a 2-day visit to the NIH Clinical Center in Bethesda, MD. Travel costs are covered by the protocol.
Read the detailed description
BACKGROUND:
Testicular germ cell tumor (TGCT) is the most common cancer in men aged 20-35, with an increasing incidence since the mid-twentieth century.
A family history of TGCT is associated with an increased risk of the disease.
Evidence suggests that there is genetic heterogeneity in familial TGCT, thereby creating opportunities for both new susceptibility gene discovery and searching for genotype/phenotype/cancer correlations.
Search for genitourinary developmental anomalies and for testicular intraepithelial neoplasia (TIN) cells which are thought to be the precursor of the vast majority of TGCT could help clarify the etiology and identify clinical features.
This project is both etiologic and clinical in its focus, and its goal is to acquire a comprehensive understanding of both the genetic and non-genetic factors which contribute to the risk of familial TGCT.
OBJECTIVES:
Ascertain new families with familial testicular germ cell tumors.
Characterize the clinical features of familial TGCT.
Determine the underlying genetic mechanism for susceptibility to TGCT in families; one specific goal is to confirm, and then to clone, the hereditary testicular cancer gene which has been mapped to chromosome Xq27.
Evaluate various parameters related to psychosocial and behavioral issues resulting from being a member of a family at increased risk of TGCT.
ELIGIBILITY:
A single family member with bilateral testicular cancer.
Individuals of both genders from a family with at least two cases of documented GCT in blood relatives (at least one of which is testicular in origin) and with at least one of the GCT cases in their family willing to participate in the study.
Men with a history of TGCT who have a monozygotic twin brother (the unaffected identical sibling must also agree to participate).
Families will be deemed ineligible if critical informative family members lacking surviving spouses and children are unable to provide germ line DNA
Minor children under age 12 will not be eligible for study participation.
DESIGN:
International collaboration between NCI's Clinical Genetics Branch and the International Testicular Cancer Linkage Consortium (ITCLC), via contribution of DNA.
Non-randomized cohort study with an estimated accrual of 75 and 100 new TGCT families over a period of 5 years and approximately 40 families willing to visit the NIH Clinical Center.
Individuals and family members will be asked to contribute baseline questionnaires as well as questionnaires regarding lifestyle, feelings, attitudes and behavior that relate to being part of a high-risk family, and DNA for gene mapping and cloning efforts.
Detailed, in-person, etiologically-oriented evaluation at the NIH Clinical Center includes a comprehensive history and physical examination, laboratory testing, and ultrasound imaging of the kidneys and gonads to identify the clinical features and seek clinically occult TGCT and TIN. CT imaging studies of the chest, abdomen, and pelvis will be performed when indicated.
Study participants will be monitored prospectively for the development of outcomes of interest by means of periodic mail and/or telephone contact. Cancer outcomes will be documented through review of medical, vital, and pathology records. Tumor tissue will be obtained whenever feasible.
As of December 2021, research activities under this protocol are limited to the follow-up collection of medical records and questionnaires from consented individuals.
- Conditions
- Testicular Cancer
- Keywords
- Genetics, Hereditary, Screening, Behavioral, Familial Testicular Germ Cell Tumor, Natural History, Testicular Cancer
- Medical subject headings
- Testicular Neoplasms, Behavior
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 | individuals from families with familial TGCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Families with Familial Testicular Germ Cell Tumors
Ascertain new familiies with FTGCTs
Measured: Ongoing
Clinical Features
Characterize the clinical features of familial TGC
Measured: Ongoing
Genetic Mechanisms
Determine the underlying genetic mechanism for susceptibility to TGCT in families
Measured: Ongoing
Psychosocial Factors
Evaluate psychosocial issues related to FGCT
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2002 (estimated)
- Study start13 Jan 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Testicular CancerStudies 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
- 749 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Douglas R Stewart, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00034424
- Sponsor's protocol ID
- 020178
- Other IDs
- 02-C-0178
- Status last verified
- 15 Apr 2026
- First submitted
- 27 Apr 2002
- Last updated
- 22 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Azevedo MF, Horvath A, Bornstein ER, Almeida MQ, Xekouki P, Faucz FR, Gourgari E, Nadella K, Remmers EF, Quezado M, de Alexandre RB, Kratz CP, Nesterova M, Greene MH, Stratakis CA. Cyclic AMP and c-KIT signaling in familial testicular germ cell tumor predisposition. J Clin Endocrinol Metab. 2013 Aug;98(8):E1393-400. doi: 10.1210/jc.2012-2838. Epub 2013 Jun 14.
PubMed 23771924Chung CC, Kanetsky PA, Wang Z, Hildebrandt MA, Koster R, Skotheim RI, Kratz CP, Turnbull C, Cortessis VK, Bakken AC, Bishop DT, Cook MB, Erickson RL, Fossa SD, Jacobs KB, Korde LA, Kraggerud SM, Lothe RA, Loud JT, Rahman N, Skinner EC, Thomas DC, Wu X, Yeager M, Schumacher FR, Greene MH, Schwartz SM, McGlynn KA, Chanock SJ, Nathanson KL. Meta-analysis identifies four new loci associated with testicular germ cell tumor. Nat Genet. 2013 Jun;45(6):680-5. doi: 10.1038/ng.2634. Epub 2013 May 12.
PubMed 23666239Schumacher FR, Wang Z, Skotheim RI, Koster R, Chung CC, Hildebrandt MA, Kratz CP, Bakken AC, Bishop DT, Cook MB, Erickson RL, Fossa SD, Greene MH, Jacobs KB, Kanetsky PA, Kolonel LN, Loud JT, Korde LA, Le Marchand L, Lewinger JP, Lothe RA, Pike MC, Rahman N, Rubertone MV, Schwartz SM, Siegmund KD, Skinner EC, Turnbull C, Van Den Berg DJ, Wu X, Yeager M, Nathanson KL, Chanock SJ, Cortessis VK, McGlynn KA. Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23. Hum Mol Genet. 2013 Jul 1;22(13):2748-53. doi: 10.1093/hmg/ddt109. Epub 2013 Mar 5.
PubMed 23462292
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
- Multidisciplinary Etiologic Study of Familial Testicular Cancer
- ClinicalTrials.gov ID
- NCT00034424
- Acronym / sponsor ID
- 020178
- Conditions
- Testicular Cancer
- Keywords
- Genetics, Hereditary, Screening, Behavioral, Familial Testicular Germ Cell Tumor, Natural History, Testicular Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 749 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 13 Jan 2003 (actual)
- First posted
- 29 Apr 2002 (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.
Background:
People with a family history of testicular cancer may be at increased risk for the disease.
Genetic and clinical studies of patients with testicular cancer and their family members may help clarify the cause of the disease and identify clinical features.
Objectives:
To characterize the clinical features of testicular cancer.
To identify genes that may lead to increased risk of the disease.
To examine emotional and behavioral issues of members of families at increased risk of the disease.
Eligibility:
Males and females from a family with at least two cases of testicular cancer in blood relatives.
Males with testicular cancer in both testicles.
Males with testicular cancer who have an identical twin.
Participants must be at least 12 years of age.
Design:
Participants may take part in Part 1 or Parts 1 and 2 of this 2-part study.
Part 1 participants:
- Provide a blood or cheek cell sample to obtain DNA for gene studies.
- Provide permission for researchers to obtain their medical records for review.
- Complete questionnaires about their personal and family medical history, exposure to factors that might influence the risk of testicular cancer, and their feelings about being a member of a family in which several members have testicular cancer.
- These data are collected from participants in their home communities.
Part 2 participants:
- All participants provide a medical history, have a complete physical examination, including routine lab tests, and have an ultrasound test of the abdomen to look at the kidneys.
- Males have an ultrasound test of the testicles and scrotum.
- Females have an ultrasound test of the pelvis to look at the ovaries, uterus and fallopian tubes.
- Males 18 years of age and older provide a semen sample.
- Some participants have computed tomography (CT) scanning of the chest, abdomen and pelvis instead of kidney ultrasound. Children under 18 years of age may have magnetic resonance imaging (MRI) instead of CT.
- These data are collected from participants during a 2-day visit to the NIH Clinical Center in Bethesda, MD. Travel costs are covered by the protocol.
Detailed description
BACKGROUND:
Testicular germ cell tumor (TGCT) is the most common cancer in men aged 20-35, with an increasing incidence since the mid-twentieth century.
A family history of TGCT is associated with an increased risk of the disease.
Evidence suggests that there is genetic heterogeneity in familial TGCT, thereby creating opportunities for both new susceptibility gene discovery and searching for genotype/phenotype/cancer correlations.
Search for genitourinary developmental anomalies and for testicular intraepithelial neoplasia (TIN) cells which are thought to be the precursor of the vast majority of TGCT could help clarify the etiology and identify clinical features.
This project is both etiologic and clinical in its focus, and its goal is to acquire a comprehensive understanding of both the genetic and non-genetic factors which contribute to the risk of familial TGCT.
OBJECTIVES:
Ascertain new families with familial testicular germ cell tumors.
Characterize the clinical features of familial TGCT.
Determine the underlying genetic mechanism for susceptibility to TGCT in families; one specific goal is to confirm, and then to clone, the hereditary testicular cancer gene which has been mapped to chromosome Xq27.
Evaluate various parameters related to psychosocial and behavioral issues resulting from being a member of a family at increased risk of TGCT.
ELIGIBILITY:
A single family member with bilateral testicular cancer.
Individuals of both genders from a family with at least two cases of documented GCT in blood relatives (at least one of which is testicular in origin) and with at least one of the GCT cases in their family willing to participate in the study.
Men with a history of TGCT who have a monozygotic twin brother (the unaffected identical sibling must also agree to participate).
Families will be deemed ineligible if critical informative family members lacking surviving spouses and children are unable to provide germ line DNA
Minor children under age 12 will not be eligible for study participation.
DESIGN:
International collaboration between NCI's Clinical Genetics Branch and the International Testicular Cancer Linkage Consortium (ITCLC), via contribution of DNA.
Non-randomized cohort study with an estimated accrual of 75 and 100 new TGCT families over a period of 5 years and approximately 40 families willing to visit the NIH Clinical Center.
Individuals and family members will be asked to contribute baseline questionnaires as well as questionnaires regarding lifestyle, feelings, attitudes and behavior that relate to being part of a high-risk family, and DNA for gene mapping and cloning efforts.
Detailed, in-person, etiologically-oriented evaluation at the NIH Clinical Center includes a comprehensive history and physical examination, laboratory testing, and ultrasound imaging of the kidneys and gonads to identify the clinical features and seek clinically occult TGCT and TIN. CT imaging studies of the chest, abdomen, and pelvis will be performed when indicated.
Study participants will be monitored prospectively for the development of outcomes of interest by means of periodic mail and/or telephone contact. Cancer outcomes will be documented through review of medical, vital, and pathology records. Tumor tissue will be obtained whenever feasible.
As of December 2021, research activities under this protocol are limited to the follow-up collection of medical records and questionnaires from consented individuals.
Study design
- Observational model
- Family based
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –individuals from families with familial TGCT |
Who may qualify
- Ages
- 12 to 77 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- A non-randomized cohort study of individuals from families with a significant history of testicular cancer.
Key inclusion criteria (21 listed)
- Patients must be members of families with familial TGCT as defined below.
- -at least two cases of documented GCT in blood relatives (at least one of which is testicular in origin),
- OR
- a single family member with bilateral testicular cancer,
- men with a history of TGCT who are one in a set of identical siblings will also be included in the study.
Key exclusion criteria (4 listed)
- There are not at least two confirmed cases of GCT in the family, (at least one of which is testicular in origin), unless there is a family member with bilateral testicular cancer;
- Deceased TGCT cases lacking both archival sources of tissue for DNA extraction AND lacking surviving spouses and children who are willing to participate in the study (the unavailability of such persons prohibits inferring the genotype of the deceased individual with TGCT);
- Critical informative family members are unwilling to participate (i.e., unwilling to provide written informed consent);
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
Families with Familial Testicular Germ Cell Tumors
Time frame: Ongoing
Ascertain new familiies with FTGCTs
Clinical Features
Time frame: Ongoing
Characterize the clinical features of familial TGC
Genetic Mechanisms
Time frame: Ongoing
Determine the underlying genetic mechanism for susceptibility to TGCT in families
Psychosocial Factors
Time frame: Ongoing
Evaluate psychosocial issues related to FGCT
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2026.
- Background: PubMed 23771924Azevedo MF, Horvath A, Bornstein ER, Almeida MQ, Xekouki P, Faucz FR, Gourgari E, Nadella K, Remmers EF, Quezado M, de Alexandre RB, Kratz CP, Nesterova M, Greene MH, Stratakis CA. Cyclic AMP and c-KIT signaling in familial testicular germ cell tumor predisposition. J Clin Endocrinol Metab. 2013 Aug;98(8):E1393-400. doi: 10.1210/jc.2012-2838. Epub 2013 Jun 14.
- Background: PubMed 23666239Chung CC, Kanetsky PA, Wang Z, Hildebrandt MA, Koster R, Skotheim RI, Kratz CP, Turnbull C, Cortessis VK, Bakken AC, Bishop DT, Cook MB, Erickson RL, Fossa SD, Jacobs KB, Korde LA, Kraggerud SM, Lothe RA, Loud JT, Rahman N, Skinner EC, Thomas DC, Wu X, Yeager M, Schumacher FR, Greene MH, Schwartz SM, McGlynn KA, Chanock SJ, Nathanson KL. Meta-analysis identifies four new loci associated with testicular germ cell tumor. Nat Genet. 2013 Jun;45(6):680-5. doi: 10.1038/ng.2634. Epub 2013 May 12.
- Background: PubMed 23462292Schumacher FR, Wang Z, Skotheim RI, Koster R, Chung CC, Hildebrandt MA, Kratz CP, Bakken AC, Bishop DT, Cook MB, Erickson RL, Fossa SD, Greene MH, Jacobs KB, Kanetsky PA, Kolonel LN, Loud JT, Korde LA, Le Marchand L, Lewinger JP, Lothe RA, Pike MC, Rahman N, Rubertone MV, Schwartz SM, Siegmund KD, Skinner EC, Turnbull C, Van Den Berg DJ, Wu X, Yeager M, Nathanson KL, Chanock SJ, Cortessis VK, McGlynn KA. Testicular germ cell tumor susceptibility associated with the UCK2 locus on chromosome 1q23. Hum Mol Genet. 2013 Jul 1;22(13):2748-53. doi: 10.1093/hmg/ddt109. Epub 2013 Mar 5.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Douglas R Stewart, 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 Testicular 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 21 inclusion and 4 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: finished, 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Families with Familial Testicular Germ Cell Tumors (time frame: Ongoing). The study lists 4 primary outcomes in all. 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 NCT00034424, which also lists 3 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.