Genetics of Familial Testicular Cancer

NCT00342537 | Completed

• 2 other identifiers: 99990407604-C-N076
• Study Type: observational
• Target: 1,842
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Testicular Cancer

Keywords

Pathology; Genetics; Testicular Cancer; Familial; Cancer Epidemiology

Outcome Measures

Primary Outcomes (1)

• Discovery of new testicular cancer susceptibilitygenes

  This outcome is the responsibility of the total ITCLC consortium, and will draw upon the collection of DNA samples from multiplecase TGCT families assembled for the purpose of gene discovery. That activity isseparate from the two substudies being proposed in the current document.

  Duration of Study

Secondary Outcomes (1)

• Characterization of the familial testicular cancer syndrome phenotype

  Duration of Study

Eligibility Criteria

• Age: 4 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Families with at least two histopathologically confirmed cases of TGCT, or a combination of TGCT and extragonadal germ cell tumor, and with DNA from at least one affected case will be enrolled at the U.S., U.K., and Norwegian study sites. For the sub-studies, data will be obtained on all family members (siblings, parents, offspring, aunts, uncles, grandparents, cousins) at up to 3 degrees of genetic relatedness to the proband.

You may qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI), 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Mai PL, Friedlander M, Tucker K, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Bonaiti-Pellie C, Heidenreich A, Albers P, Bodrogi I, Geczi L, Olah E, Daly PA, Guilford P, Fossa SD, Heimdal K, Liubchenko L, Tjulandin SA, Stoll H, Weber W, Easton DF, Dudakia D, Huddart R, Stratton MR, Einhorn L, Korde L, Nathanson KL, Bishop DT, Rapley EA, Greene MH. The International Testicular Cancer Linkage Consortium: a clinicopathologic descriptive analysis of 461 familial malignant testicular germ cell tumor kindred. Urol Oncol. 2010 Sep-Oct;28(5):492-9. doi: 10.1016/j.urolonc.2008.10.004. Epub 2009 Jan 22.

  PMID: 19162511 BACKGROUND

• Nathanson KL, Kanetsky PA, Hawes R, Vaughn DJ, Letrero R, Tucker K, Friedlander M, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Chompret A, Bonaiti-Pellie C, Heidenreich A, Olah E, Geczi L, Bodrogi I, Ormiston WJ, Daly PA, Oosterhuis JW, Gillis AJ, Looijenga LH, Guilford P, Fossa SD, Heimdal K, Tjulandin SA, Liubchenko L, Stoll H, Weber W, Rudd M, Huddart R, Crockford GP, Forman D, Oliver DT, Einhorn L, Weber BL, Kramer J, McMaster M, Greene MH, Pike M, Cortessis V, Chen C, Schwartz SM, Bishop DT, Easton DF, Stratton MR, Rapley EA. The Y deletion gr/gr and susceptibility to testicular germ cell tumor. Am J Hum Genet. 2005 Dec;77(6):1034-43. doi: 10.1086/498455. Epub 2005 Oct 24.

  PMID: 16380914 BACKGROUND

• Crockford GP, Linger R, Hockley S, Dudakia D, Johnson L, Huddart R, Tucker K, Friedlander M, Phillips KA, Hogg D, Jewett MA, Lohynska R, Daugaard G, Richard S, Chompret A, Bonaiti-Pellie C, Heidenreich A, Albers P, Olah E, Geczi L, Bodrogi I, Ormiston WJ, Daly PA, Guilford P, Fossa SD, Heimdal K, Tjulandin SA, Liubchenko L, Stoll H, Weber W, Forman D, Oliver T, Einhorn L, McMaster M, Kramer J, Greene MH, Weber BL, Nathanson KL, Cortessis V, Easton DF, Bishop DT, Stratton MR, Rapley EA. Genome-wide linkage screen for testicular germ cell tumour susceptibility loci. Hum Mol Genet. 2006 Feb 1;15(3):443-51. doi: 10.1093/hmg/ddi459. Epub 2006 Jan 11.

  PMID: 16407372 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Formalin-fixed, paraffin-imbedded H\&E tissue sections from familial and sporadic testicular cancer tumors.

MeSH Terms

Conditions

Testicular Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders

Study Officials

• Mary L McMaster, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: OTHER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2006
• First Posted: June 21, 2006
• Study Start: January 2, 2004
• Primary Completion: December 31, 2019
• Study Completion: July 14, 2020
• Last Updated: July 17, 2020

Record last verified: 2020-07

Locations

US (1)