Genetics of Familial Testicular Cancer
| Status: | Completed |
|---|---|
| Conditions: | Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 4 - 100 |
| Updated: | 4/6/2019 |
| Start Date: | December 31, 2003 |
Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Studies of Familial Testicular Germ Cell Tumors
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.
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.
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.
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.
- 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.
We found this trial at
1
site
9609 Medical Center Drive
Bethesda, Maryland 20892
Bethesda, Maryland 20892
1-800-422-6237
National Cancer Institute , 9000 Rockville Pike The National Cancer Institute (NCI) is part of...
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