Nevada Cancer Institute

Funding for Human Subjects Research:

DOE: Office of Biological and Environmental Research (OBER)

$966,000.00 (Est.) for: Calendar Year 2005
Percent of funding associated with the use of human subjects: 100

Information on Use of Human Subjects:

This project does not involve the use of multiple protocols/subprojects.

Identifier or number: NVCI005s

Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Nevada Cancer Institute
Most recent approval: 01/24/05
IRB approval number: 109650

Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 32
Reporting period for number of human subjects: Fiscal Year 2005

Type(s) of Human Subjects Involvement:

Collection of personally identifiable bodily materials (blood or blood products, urine, cells, tissue, teeth, organs, excreta, etc):

• Using bodily materials collected specifically for this project.

(a. Objectives, b. Methodology, c. Ionizing Radiation, Radioactive Substances, or Chemical Substances to which human subjects are exposed, d. Involvement of Human Subjects [d.1. procedures used, d.2. risks if any])

1.0 PURPOSE
1.1 Primary Objective
The overall goal of this project is to develop simple, inexpensive, and reproducible tests to screen for the presence of melanoma and other cancers initially using volunteers from the Hotel Restaurant Employee International Union (HEREIU), Culinary Union 226 and Bartenders Local Union 165. A major objective of the project is to establish a general screening program for the early detection of melanoma and other skin cancers that involves the collection of whole-body digital photographic images and computer-assisted comparison of serial images from the same individual to detect moles, and other skin growths that have changed size, shape or color in the time interval between image collections. Any skin abnormalities detected by digital imaging would then be subjected to infrared image analysis which would determine the thickness of "suspicious" nevi (a non-surgical method for establishing a Breslow score) and measure the vascular density under the "suspicious" nevi (a measure of growth potential of melanotic or premelanotic lesions). Positive indication of precancerous or cancerous lesions would trigger immediate referral to a dermatologist for follow-up evaluation. Union member volunteers will be divided into two groups: one group will contain individuals who have no prior history of skin cancer in their family, while the second group will contain individuals with a prior history. The first group will have whole body digital images collected once a year; the second group will be imaged every six months. Volunteers will be asked to provide blood samples at the time of each imaging for subsequent studies designed to identify genetic or serum protein markers indicating predisposition to, or early stages of, skin cancer.

A second objective will be to use the blood samples collected from volunteers to screen for other cancers. DNA prepared from buffy coats will be used for genetic screening projects, including screening for genetic markers that predispose to breast and ovarian cancers (e.g., BRCA1 and BRCA2 mutations) and cardiovascular disease risk (e.g., the Factor V Leiden mutation). Investigators on this project (Drs. Ward and Bray-Ward) have developed a rapid and inexpensive optical thin-film biosensor technology to screen for hundreds of such mutations simultaneously. We will use this technology to carry out this facet of the project. In addition, serum/plasma will be used for identification of serum/plasma biomarkers for cancer types such as ovarian and kidney cancer, as funding for such projects becomes available. Drs. Ward and Bray-Ward, in conjunction with collaborators at Yale University, have identified a set of five (5) proteins in serum the level of which, collectively, can discriminate women who have ovarian and/or breast cancer from women who do not. Complete concordance in segregating disease-free from disease-bearing individuals has been achieved to date (9-15-04) in a blind study of over 100 women. We propose to identify women volunteers of HEREIU who are at risk for ovarian/breast cancer and utilize their serum for validation of these serum biomarkers.

1.2 Specific Aim 1: Collection and Storage of Blood Samples and Clinical Database Development
Volunteers who are willing to participate in a cancer surveillance study and donate blood for clinical research on melanoma and other cancers will be enrolled. Blood samples will be collected from each individual and stored for subsequent proteomic and genetic studies (including but not limited to ovarian/breast cancer and cardiovascular disease risk).

1.3 Specific Aim 2: Clinical Screening
In addition to annual clinical examination or regular clinic visits that include visual identification of melanomas, study participants will be offered melanoma screening by whole body scans, performed using a unique digital imaging device. Epiluminescence digital images of whole body surfaces will be recorded. Serial digital images will be analyzed by commercially available computer software with algorithms that compare the size, shape, and pigmentation of nevi in digital images to identify significant changes with great sensitivity. Digital images will be stored in the clinical database for analysis and for comparison with scans done in following years. When comparative digital image analysis suggests atypical shape, color, or growth of skin structures, infrared imaging of suspicious nevi will be implemented in order to determine nevi thickness and the vascular density under and surrounding each such nevus. A dermatologist referral will be requested immediately and the image data provided to the physician.

1.4 Specific Aim 3: Genetic Analysis
Optical thin-film biosensor chip technology will be used to genotype all blood samples acquired for single nucleotide polymorphisms (SNPs) known to be related to occurrence or progression of melanoma and other cancers and to scan exons and promoter regions of key genes for single-base changes. Exons and promoter regions with nucleotide changes will be sequenced to identify nucleotide changes predicted to create changes in protein expression level/function. Information regarding risk for cancers will be provided to the primary physician of individuals that appear by genetic analysis to be at increased risk.

1.5 Specific Aim 4: Biostatistical Analysis
Clinical, demographic, genetic, and digital imaging data will be analyzed by Dr. H. Zhao, the consultant biostatistician, to stratify the population into relative risk groups. If a multiparametric data signature is obtained that correlates with increased melanoma risk, data for all individuals will be reassessed to determine probable risk and the need for more intensive surveillance for specific individuals.

1.6 Specific Aim 5: Tissue Procurement/Tumor Tissue Banks
During the initial stages of this project our clinical samples will largely, if not entirely, be comprised of blood samples. With the passage of time, we anticipate that many volunteers in the program will be diagnosed with various types of cancer. These individuals will be requested to donate tumor and surrounding normal tissues (tissues normally collected during tumor removal to determine tumor margins). We propose to create a tumor tissue bank which, in conjunction with pre- and post-disease blood samples, will be used in genomic and proteomic studies for the identification of disease markers and markers for monitoring response to subsequent chemotherapy.