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Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Studies of Familial Testicular Germ Cell Tumors

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Trial Information

Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Studies of Familial Testicular Germ Cell Tumors

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

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.

Inclusion Criteria


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.

Type of Study:


Study Design:


Principal Investigator

Mark H Greene, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

December 2003

Completion Date:

Related Keywords:

  • Testicular Cancer
  • Pathology
  • Central Review
  • Cancer Risk
  • Hereditary Cancer Syndrome
  • Testicular Neoplasms