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Genetics of Familial Testicular Cancer

This study has been completed.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ) Identifier:
First received: June 19, 2006
Last updated: April 21, 2017
Last verified: August 24, 2016

This study is a collaboration between the Clinical Genetics Branch of the National Cancer Institute and the International Testicular Cancer Linkage Consortium (ITCLC). The primary goal of the ITCLC is mapping and cloning susceptibility genes for familial TGCT. The objectives of the current study are to:

  • Identify the genes responsible for testicular germ cell tumor (TGCT) (testicular cancer) in families with an inherited tendency to develop the disease
  • Determine if the genes which predispose to developing testicular cancer also increase the risk of other specific types of cancer among first- and second-degree relatives of patients with TGCT
  • Determine if the microscopic appearance of familial testicular cancers is different from that of non-familial TGCT

Patients and family members recruited by the ITCLC in the United Kingdom, the Netherlands, and Norway are eligible for this study. Individuals with the following medical criteria may participate:

  • Patients with testicular germ cell cancer who have at least one other blood relative with the disease
  • Family members of patients (first- and second-degree relatives)

Participants undergo the following procedures:

  • Fill out questionnaires for providing information about a history of cancer in all blood relatives, including parents, siblings, children, grandparents, aunts, uncles, and cousins, and a history of undescended testes in male blood relatives. Participants may be asked permission to contact family members to request their help in the study as well.
  • Provide a blood sample for genetic testing related to TGCT (except in children under 16 years old).
  • Review of medical records and examination of tumor specimen (patients with TGCT only).
  • Confirmation of the diagnosis of other types of cancer in these same families (medical records, pathology repots)
  • Review of the testicular cancer tissue obtained at the time of surgery from members of multiple case families, and comparison of these findings with a series of TGCT which have developed in men without a family history.

Testicular Cancer

Study Type: Observational
Study Design: Observational Model: Family-Based
Time Perspective: Other
Official Title: Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Studies of Familial Testicular Germ Cell Tumors

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Discovery of new testicular cancer susceptibilitygenes [ Time Frame: Duration of Study ]

Secondary Outcome Measures:
  • Characterization of the familial testicular cancer syndrome phenotype [ Time Frame: Duration of Study ]

Estimated Enrollment: 2600
Study Start Date: December 31, 2003
Detailed Description:

Familial clustering of testicular germ cell tumors (TGCT) is well-documented, and a family history of TGCT is associated with an increased risk of this disease. The International Testicular Cancer Linkage Consortium (ITCLC) has assembled 350 multiple case TGCT families in support of a linkage effort that provisionally mapped a susceptibility gene to chromosome Xq27 in a subset of these kindreds. However, familial TGCT is genetically heterogeneous, thus increasing the need for meticulous case definition and classification in ongoing genetic and etiologic studies. The histopathologic classification of TGCT is very complicated; few pathologists have extensive experience reviewing this uncommon tumor. Basing epidemiologic studies upon local pathology reports may result in failure to recognize etiologically critical TGCT subsets of the kind which have been central to suspecting and defining various hereditary cancer syndromes, such as the multiple inherited renal cancer disorders.

Few studies have addressed the risk of cancer among relatives of sporadic TGCT patients. Recent reports suggest a 20% increase in overall cancer risk among first-degree relatives of TGCT patients and site-specific excess cancer risks in male relatives and in the mothers of TGCT patients. These cancer sites constitute diseases for which there is some prior evidence to suggest a genetic relationship to TGCT. Identification of other cancers as part of the familial TGCT disease spectrum would both provide clinically relevant insight into this syndrome, and enhance the statistical power of gene-seeking linkage analysis.

We propose two studies, each targeting the ITCLC set of high-risk TGCT families, none of which come from the US: (a) Centralized Pathology Review of Familial TGCT; and (b) The Occurrence of Cancer Other than Germ Cell Tumors in TGCT Families. Data will be provided by three of the largest ITCLC contributors; each will contact TGCT probands and their relatives and collect the primary data under their familial and non-familial TGCT, and perform the data analysis for both studies. NCI will neither seek nor receive individual identifying information from any participant. Currently, our UK collaborator has completed acquisition of a Federal Wide Assurance (FWA) and local ethical review. Since this group is contributing 70% of the families in these two projects, we now bring that component before the NCI Special Studies IRB. We shall return to the IRB for review of the other two contributors upon completion of their local ethical review process.


Ages Eligible for Study:   4 Years to 100 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

The criterion establishing familial TGCT is the presence of at least two cases of documented GCT in blood relatives.

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. Estragonadal sperm cell tumors will also be included.

Germ cell-derived histologies including: seminoma, 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.

  Contacts and Locations
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Please refer to this study by its identifier: NCT00342537

United States, Maryland
National Cancer Institute (NCI), 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Norwegian Radium Hospital
Oslo, Norway
United Kingdom
UCL Hospitals Trust
London, United Kingdom
Institute of Cancer Research/Haddow Laboratories
Sutton, United Kingdom
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Mark H Greene, M.D. National Cancer Institute (NCI)
  More Information


Responsible Party: National Cancer Institute (NCI) Identifier: NCT00342537     History of Changes
Obsolete Identifiers: NCT00897598
Other Study ID Numbers: 999904076
Study First Received: June 19, 2006
Last Updated: April 21, 2017

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

Additional relevant MeSH terms:
Testicular Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Endocrine System Diseases
Testicular Diseases
Gonadal Disorders processed this record on April 25, 2017