Germline Alterations of Tumor Susceptibility Genes in New York Cancer Patients

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.

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.