Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Testicular Neoplasms

Endocrine Gland Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Male Urogenital Diseases

Endocrine System Diseases

Testicular Diseases

Gonadal Disorders

Germ Cells Tumors

Testicular Germ Cell Tumor

Mary L McMaster, M.D.

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.

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.

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

Genetics of Familial Testicular Cancer

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

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.

1. We will quantify the risks of cancers (both all sites combined and site-specific risks) other than TGCT in the relatives of multiple-casefamilies. 2. We will perform a central pathology review in which the familial TGCT cases will be compared with age-matched unselected TGCT cases, to determine whether there are unique histologic features which characterize the familial cases.

National Cancer Institute (NCI)

Digestive System Diseases

Symptoms and General Pathology

Adenocarcinoma

Pancreatic Neoplasms

Cysts

Pancreatic Diseases

Pancreatic Cyst

Mucocele

Cystadenoma

Cystadenoma, Serous

Neoplasms, Cystic, Mucinous, and Serous

Pancreatic Intraductal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pathological Conditions, Anatomical

Pancreatic Cancer

Gastrointestinal Agents

All Drugs and Chemicals

Pancrelipase

Pancreatin

The registry will be populated with a retrospective cohort of patients previously identified as having pancreatic cysts.

The prospectively enrolled patients in this study are the primary population of interest.

There are no study-specific interventions, as this is a prospective registry. However, patients will be asked to complete approximately 1-2 hours worth of surveys on things such as demographics, medical and surgical history, and pancreatic cyst-specific questionnaires.

Survey

Charysa Santos, BS

Kimberly S Kirkwood, MD

M.D.

Kimberly Kirkwood, MD

Paige M Bracci, PhD, MPH, MS

Pancreatic cysts are found incidentally on 15-50% of CT and MRIs for all indications and their prevalence is increasing. Many of these cysts may be precursors to pancreatic cancer, and thus pose a substantial risk, however, the vast majority are benign. Increased detection of pancreatic cysts provides an opportunity to diagnose pancreatic malignancy at an early, curable stage yet also increases the potential to over-treat clinically insignificant lesions. This presents a clinical challenge to prevent unnecessary resection of indolent disease, with associated risks of infections, bleeding, diabetes, and costly disability. Unfortunately, there is little information on the epidemiology and natural history of pancreatic cysts to help guide management.

This study develops a large, prospectively managed, electronic, patient-directed pancreatic cyst registry based at UCSF. The UCSF Pancreatic Cystic Lesions Registry (PANC Cyst) will facilitate work to improve clinical care and understanding of pancreatic cysts by prospective follow-up of patients with cystic lesions, especially the diagnostically challenging small cysts, to identify factors related to cyst formation and progression to malignancy. Longitudinal data capture that includes clinical outcomes will also enable us to more precisely define anatomic, radiographic and biomarker information that can be used to differentiate populations of patients for whom surgery is indicated, surveillance is warranted, or no further evaluation is necessary.

Patients in this study will have the option of donating blood for biobanking, approximately 10cc of plasma and 10cc of serum. Patients will also have the opportunity to donate a saliva sample at the time of study registration, or at a later date.

Further, samples that are routinely collected for diagnostic purposes may be collected and banked at the time of their clinically routine procedure. If a patient consents to the use of extra material for research purposes, the biological samples will be banked and the blood, and/or pancreatic juice/cystic fluid, tissues, and saliva will be used for identification and characterization of potential biomarkers from de-identified samples.

UCSF PANC Cyst Registry

Population-Based Analysis of Neoplastic Changes in Cystic Lesions of the Pancreas.

While not the primary outcome measure, the development of cancer from a pancreatic cyst is a critically important study endpoint, which the investigators do not expect to be frequent occurrence.

If a patient with a pancreatic cyst experiences no or minimal change in size, and no development of worrisome or high-risk stigmata (Tanaka 2017), this will be considered to be an indolent lesion. Most patients will fall under this category.

University of California, San Francisco

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Genetics of Familial Testicular Cancer	NCT00342537	Testicular Canc...		4 Years - 100 Years	National Institutes of Health Clinical Center (CC)
UCSF PANC Cyst Registry	NCT04291651	Pancreatic Cyst Pancreatic Neop... Pancreatic Canc... Pancreatic Dise... Pancreatic Intr... Intraductal Pap... Pancreatic Duct... Mucinous Cyst	Survey	18 Years -	University of California, San Francisco

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