Germline Alterations of Tumor Susceptibility Genes in New York Cancer Patients

Memorial Sloan Kettering Cancer Center (MSK)

Status: Active, not recruiting

Conditions: Breast Cancer; Bladder Cancer; Colon Cancer; Lung Cancer; Kidney Cancer; Ovarian Cancer; Prostate Cancer

Treatments: Genetic: PCR/PCR/LDR Strategy

Study type: Interventional

Funder types: Other

Identifiers

NCT00579514

00-014

Details and patient eligibility

About

The basic premise of this research proposal is to determine whether there is any significant association between germline polymorphisms and cancers of colon, bladder, breast, testicular, prostate, ovaries, kidney, lung, lymphoid organs, and head and neck. This is an exploratory study designed to generate hypotheses for further research.

Full description

To establish significant correlations between genetic polymorphisms and cancer, a largescale, systematic comparison of genetic alterations utilizing a case-control methodology is proposed. To date, such studies have been limited due to the large number of samples necessary for obtaining statistical significance, and the lack of rapid and accurate methods to screen for genetic polymorphisms. We propose to utilize an anonymized design to obtain DNA from residual material from routine diagnostic blood tests, to link these samples to a limited set of clinical variables, and to test for the frequency of candidate low-penetrance cancer susceptibility alleles. These data will be combined with similar data from a control group of age- and ethnically-matched volunteers for a related cohort study to be conducted separately. Polymorphisms to be screened for include those involving the genes PTEN, APC, TGF βR-I, BLM, CHK2, a p85 phosphoprotein, ATM, ER, PR, MCP-1, MPIF, CCR2/5, CCR3, and SULT1A1. Cancers to be included are breast, bladder, kidney,colon, testicular, lung, prostate, ovarian, lymphoid neoplasms, and head and neck carcinomas. Genes with SNPs known to be relevant for either the development or treatment of lymphoid malignancies will also be targeted. Specifically, candidate genes will be selected from 1) cytokine signaling, 2) DNA repair, and 3) apoptosis regulatory pathways.

Enrollment: 21,081 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with a histologic diagnosis of cancer of the colon, breast, bladder, kidney, testicles, lungs, prostate, head and neck, or lymphoid organs, who have donated a diagnostic blood sample as either an inpatient or outpatient at MSKCC.
• All patients who have two or more histologic diagnoses of the same primary tumor type involving the above sites.
• Patients of Ashkenazi Jewish ancestry with a histologic diagnosis of cancer of any type.
• Samples ascertained as part of protocol 98-024A(1) are also eligible for ascertainment in this study.

Exclusion criteria

• MSKCC patients without a histologic diagnosis of cancer of the breast, bladder, kidney, colon, testicles, lungs, prostate, or lymphoid malignancy (including all types of lymphoma) will not be eligible for the AMDeC sponsored component of the study.

Trial design

Primary purpose: Screening

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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21,081 participants in 2 patient groups, including a placebo group

1

Active Comparator group

Description:

All incident second primary cancers of colon, breast, bladder, kidney, prostate, ovarian cancer lung cancer and lymphoid cancer diagnosed between 1999 and present will be included in the secondary design to compare second primary cancer "cases" and first primary "controls".

Treatment:

Genetic: PCR/PCR/LDR Strategy

2

Placebo Comparator group

Description:

Controls will be volunteer blood donors from the New York Blood Center as well as normal volunteers from other AMDeC sites.

Treatment:

Genetic: PCR/PCR/LDR Strategy