Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Breast/Ovarian Cancer
Condition: Familial Ovarian Cancer; Familial Breast Cancer; BRCA1-associate Malignancies; BRCA2-associated Malignancies
MeSH terms: Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Study type: Observational

Summary: 
      Individuals and families with known or suspected syndromes that include breast, ovarian or
      genetically-related cancers are enrolled in this family study, which is a syndrome-specific
      sub-set of the long-standing DCEG Human Genetics Program umbrella family studies protocol
      (78-C-0039). Cancer outcomes are documented through review of medical, vital, and pathology
      records. Selected individuals and family members are asked to complete questionnaires to
      assess etiologic risk factors and to undergo clinical evaluations specifically tailored to
      the relevant familial syndrome. Study participants are monitored prospectively for the
      development of outcomes of interest, typically by means of periodic mail or telephone
      contact. In selected instances, subjects may return to the Clinical Center periodically for
      study-specific follow-up examinations. Study participants are asked to donate biologic
      specimens to be used in the laboratory search for cancer etiology and mechanisms of
      carcinogenesis. DNA and serial serum samples will be collected. Tumor tissue will be obtained
      whenever feasible.

      Clinical genetic testing for tumor susceptibility gene(s) mutations and risk notification
      will be offered consistent with ASCO guidelines when reasonable individual cancer risk
      estimates can be delivered, and only to those participants who choose to know their
      individual genetic status after appropriate education and counseling. The testing will be
      conducted exclusively in Clinical Laboratory Improvement Amendments (CLIA)-licensed
      laboratories. Clinical genetic testing and risk notification are entirely optional and do not
      affect subject eligibility for other aspects of the protocol. A separate consent procedure
      and consent form will be used for genetic testing and risk notification.

      This protocol, developed in response to recommendations developed by the Clinical Center IRB,
      is intended to:

        1. Provide a mechanism under which the Clinical Genetics Branch can honor the commitment
           made to the members of over 60 hereditary breast/ovarian cancer families which have been
           participated in various Human Genetics Program research studies conducted over the past
           3 decades to provide genetic counseling,

           clinical germline mutation testing, and consultative services now that several of the
           major breast/ovarian cancer susceptibility genes have been identified;

        2. Provide a mechanism through which new families with various familial syndromes
           associated with an increased risk of breast and ovarian cancer can be studied, as
           research interests in these syndromes evolve over time; and

        3. Create a resource of well-characterized, carefully documented high-risk families to
           facilitate the development of new etiologic and translational research studies in the
           future.

      While we do not offer specific anti-cancer therapy as part of this protocol, we provide
      assistance to ensure that study participants who require treatment for problems that develop
      during the course of the study are referred to appropriate health providers. We

      remain available to provide advice and consultation related to the management of the familial
      cancer syndrome to study participants and their health care providers.
    

Detailed description: 
      Individuals and families with known or suspected syndromes that include breast, ovarian or
      genetically-related cancers are enrolled in this family study, which is a syndrome-specific
      sub-set of the long-standing DCEG Human Genetics Program umbrella family studies protocol
      (78-C-0039). Cancer outcomes are documented through review of medical, vital, and pathology
      records. Selected individuals and family members are asked to complete questionnaires to
      assess etiologic risk factors and to undergo clinical evaluations specifically tailored to
      the relevant familial syndrome. Study participants are monitored prospectively for the
      development of outcomes of interest, typically by means of periodic mail or telephone
      contact. In selected instances, subjects may return to the Clinical Center periodically for
      study-specific follow-up examinations. Study participants are asked to donate biologic
      specimens to be used in the laboratory search for cancer etiology and mechanisms of
      carcinogenesis. DNA and serial serum samples will be collected. Tumor tissue will be obtained
      whenever feasible.

      Clinical genetic testing for tumor susceptibility gene(s) mutations and risk notification
      will be offered consistent with ASCO guidelines when reasonable individual cancer risk
      estimates can be delivered, and only to those participants who choose to know their
      individual genetic status after appropriate education and counseling. The testing will be
      conducted exclusively in Clinical Laboratory Improvement Amendments (CLIA)-licensed
      laboratories. Clinical genetic testing and risk notification are entirely optional and do not
      affect subject eligibility for other aspects of the protocol. A separate consent procedure
      and consent form will be used for genetic testing and risk notification.

      This protocol, developed in response to recommendations developed by the Clinical Center IRB,
      is intended to:

        1. Provide a mechanism under which the Clinical Genetics Branch can honor the commitment
           made to the members of over 60 hereditary breast/ovarian cancer families which have been
           participated in various Human Genetics Program research studies conducted over the past
           3 decades to provide genetic counseling, clinical germline mutation testing, and
           consultative services now that several of the major breast/ovarian cancer susceptibility
           genes have been identified;

        2. Provide a mechanism through which new families with various familial syndromes
           associated with an increased risk of breast and ovarian cancer can be studied, as
           research interests in these syndromes evolve over time; and

        3. Create a resource of well-characterized, carefully documented high-risk families to
           facilitate the development of new etiologic and translational research studies in the
           future.

      While we do not offer specific anti-cancer therapy as part of this protocol, we provide
      assistance to ensure that study participants who require treatment for problems that develop
      during the course of the study are referred to appropriate health providers. We remain
      available to provide advice and consultation related to the management of the familial cancer
      syndrome to study participants and their health care providers.
    

Observational model: Family-Based
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        Individuals and families with known or suspected syndromes that include breast, ovarian or
        genetically-related cancers are enrolled in this family study.
      
Keywords: Counseling/behavioral/psychosocial; Gene discovery; Cancer prevention; Risk-reduction; Hereditary; Natural History; Breast Cancer; Ovarian Cancer; Cowden Syndrome; Peutz-Jegher Syndrome; Li-Fraumeni Syndrome