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Cause of Familial Testicular Cancer

Completed
Conditions
Testicular Cancer
Registration Number
NCT00034424
Lead Sponsor
National Cancer Institute (NCI)
Brief 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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
749
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Genetic MechanismsOngoing

Determine the underlying genetic mechanism for susceptibility to TGCT in families

Clinical FeaturesOngoing

Characterize the clinical features of familial TGC

Families with Familial Testicular Germ Cell TumorsOngoing

Ascertain new familiies with FTGCTs

Psychosocial FactorsOngoing

Evaluate psychosocial issues related to FGCT

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

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