Mr. Peter Moberg
St. Mary's Hospital and Medical Center
P.O. Box 1628
Grand Junction, CO 81501
Phone: 970-244-2000
Fax: 970-241-7510
Email: n/a
Projects are approved by an IRB located at: St. Mary's Hospital and Medical Center.
The approving IRB does not operate under a Multiple Project Assurance (MPA) recognized by DOE or by the Department of Health and Human Services (HHS).
Number of Human Subjects Projects reported: 2
Project Identifier: SMHMC-94-FG03-94ER61842
Project Title:
Examination of Genetic Alterations in Pre-neoplastic and Neoplastic Lesions of the Lung From Uranium Miners
Principle Investigator:
Dr. Marshall W. Anderson
Project started in: 1994
Project Funding Information:
Project received funding in Fiscal Year 1995.
Project used human subjects in Fiscal Year 1995.
Funding Sources:
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: November 01, 1995
IRB Approval Number: 95-0007
Number of Human Subjects in the Last Reporting Period for this Project: 151
(Reporting periods vary.)
Type of Human Subjects Involvement:
The main emphasis of this project is the morphologic diagnosis of early lung cancer lesions. Current studies at St. Mary's Hospital reveal improved survival utilizing sputum cytology, while national statistics for early detection fail to duplicate this finding. An opportunity exists to better understand lung tumorigenesis in uranium miners by molecular analysis of gene alterations in both preneoplastic and malignant neoplasms. Our objectives are to examine the genetic alterations associated with the initiation and progression of radon-induced lung cancer. Genetic alterations will be identified in both preneoplastic lesions and malignant neoplasms to ascertain the stage of tumor development at which protooncogenes and tumor suppressor genes are mutated/lost. Three long-term goals are as follows: 1) To detect early genetic and/or cellular alterations which ultimately could lead to diagnostic modalities for the early detection of lung cancer; 2) To determine the mechanism of radon-induced lung cancer in uranium miners; and 3) To utilize data on uranium miners to assess the effect of low level radon exposure in the general population. Our research will generate comprehensive tracheal bronchial trees from lung cancer patients to aid in the characterization of lung tumor progression. Nonsmall cell lung carcinomas and their precursor lesions will be examined from the following groups of patients: Group I -- uranium miners who were smokers; Group II -- uranium miners who were not smokers; and Group III -- smokers who were not miners. Comparisons between Groups I and III will generate data to address the hypothesis that radon exposure plus smoking either induces different genetic lesions or induces lesions at different stages of tumor development than does smoking alone. Observations made on Group II will either confirm or refute the comparisons between Groups I and III.
Human Subjects:
This proposed study has been approved by the St. Mary's Hospital and Medical Center Institutional Review Board. Archival material on patients diagnosed with primary bronchogenic carcinoma will make up this study group. The selection of these study subjects will primarily include men older than 50 years of age based on the known demographic characteristics of uranium mine workers. Subjects will also reflect the ethnic and racial composition of the mining industry of the Colorado Plateau. The clinical subjects chosen for parallel studies will be selected from the St. Mary's Hospital total patient base. The hospital does not discriminate on the basis of age, race, color, creed, or ethnic background.
The subjects for this proposal will include patients who have histologically confirmed primary bronchogenic carcinoma, the majority having documentation of radon progeny exposure.
1. Underground Uranium Workers: Subjects enrolled in the ongoing underground uranium miner lung cancer surveillance program will be considered for the study. Cases will be selected as to histologic classification, availability tissue samples and documented smoking, occupational exposure and other risk factors for lung cancer.
2. Clinical specimens: Subjects who have surgical resections at St. Mary's Hospital or the Veterans Administration Hospital in Grand Junction for primary bronchogenic carcinoma will be considered for this study. Cases will be selected as to histological classification, tissue samples, documented smoking history, occupational exposure, and other risk factors for lung cancer.
3. Risks: Archived biological samples will be used in this study.
4. Procedures of protection of "Patient Rights" regarding the use of archival samples: Confidentiality will be maintained at all times. Samples used for analysis will be coded with the "Early Lesion Study" (ELS) prefix, year of study enrollment, and enrollment number (ELS-93-000). Subject keys will be maintained in a subject file, which will be stored with all study information in a locked cabinet with controlled access.
5. Risk/Benefit: This study provides lung cancer patients and their families with a unique opportunity to better understand the molecular makeup and possible pathways to lung cancer genesis. The knowledge gained from such studies is critical to the issues of environmental exposure -- both in the work place and in the home -- from radon progeny, its cause and effect on the development of this disease. Any important findings related to a specific individual that may prove critical to the health maintenance of his family will be communicated to his physician by the principal investigator with a complete and thorough explanation as best we understand the information at that time.
6. Risk Manager: In the event a subject or a family member questions the use of archival tissue samples or the results of such studies, the person(s) involved will be directed to the Risk Manager's office for consultation.
Project Identifier: SMHMC-95-FG03-95ER72060
Project Title:
Identification of Human Lung Cancer Susceptibility Genes
Principle Investigator:
Dr. Marshall W. Anderson
Project started in: 1995
Project Funding Information:
Project received funding in Fiscal Year 1995.
Project used human subjects in Fiscal Year 1995.
Funding Sources:
This is a new grant which was recommended for approval on April 26, 1995. We were informed on the amount of funding we would receive ($199,674), but have not received funds as of
Project involves use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 2
Protocol/Subproject # 1
Protocol/Subproject Identifier: 093-001
IRB Review:
Type of Review: Full Board
Most Recent Approval: June 01, 1995
IRB Approval Number: 093-001
Number of Human Subjects in the Last Reporting Period for this Project: 381
(Reporting periods vary.)
Type of Human Subjects Involvement:
Lung cancer is the leading cause of cancer death in the United States and Western Europe. Improvements in early detection coupled with the identification of a gene or genes which predispose individuals to lung cancer could help reduce the death rate for this disease. There is considerable evidence that genetic predisposition may be an important factor in the development of lung cancer. First, only 20% of smokers develop lung cancer. Second, genetic epidemiologic studies of familial lung cancer imply the involvement of a susceptibility gene(s). It was hypothesized that the genetic predisposition to lung cancer is expressed only in individuals who smoke or are exposed to other environmental insults such as radon. Confirmation of a genetic predisposition for lung cancer can be accomplished by linkage analysis to localize the putative susceptibility gene(s) to a specific chromosomal region(s). The strength of linkage analysis is dependent upon the establishment of lung-cancer-susceptible kindreds for which tissue samples are available and the history of tumor incidence exists for two, preferably more, generations. Four goals of this proposal are: 1) to generate pedigrees for lung-cancer-susceptible families and collect tissue samples from family members for genotyping analysis; 2) to genotype DNA from family members with appropriate markers; 3) to perform linkage analysis with the genotyping data to identify a potential locus (or loci) that may be involved in lung cancer susceptibility; and 4) to begin to identify the susceptibility gene(s). The long-term objective is to characterize the susceptibility gene(s) and develop blood tests to identify individuals who are predisposed to develop lung cancer.
Human Subjects:
This study was approved by the St. Mary's Hospital and Medical Center Institutional Review Board on August 11, 1993 and is being submitted for approval by the Medical College of Ohio, Toledo, Institutional Review Board. The hospitals serve wide geographic regions and do not discriminate on the basis of age, race, color, creed, or ethnic background.
Study subjects will be members of lung-cancer-susceptible families and families must contain more than one first- and/or second-generation blood related member that had a tissue diagnosed, primary lung carcinoma. Study subjects will be asked to sign a medical release of information form and will be interviewed in order to obtain accurate medical, smoking, occupational, family histories, and genealogical information. Potential lung cancer families have been and will continue to be selected from the uranium worker's study, from clinical pathology patients at St. Mary's Hospital and Medical Center, and from information obtained from primary care physicians and oncologists. Similar procedures will be utilized at the Medical College of Ohio, Toledo. Permission for subject contact will originate with primary care physician and/or other family members. The purpose and nature of the study will be explained to the family contact person and all other potential family members by a scientist or an appointed research staff member.
All tissue samples including blood, paraffin embedded tissues, cytological specimens, and fresh frozen tissue samples will be collected from study subjects for research purposes. All information and specimens will be obtained and handled in a confidential manner. The risk of unauthorized persons having access is minimal. Enrollment is voluntary and any enrollee may terminate his or her participation in the study without any consequences. Confidentiality of all subjects' clinical, occupational, genealogical, and specimen acquisitions will be maintained at all times.
Standard phlebotomy techniques will be practiced to protect against or minimize any potential risk for the collection of blood specimens. Participants will be given instructions on care of the venipuncture site. The subjects will be monitored for any stress during interview and/or blood draw. The procedure will be terminated immediately if participant shows signs of mental or physical distress. The phone number for the Risk Manager's office will be given in the event physical or mental complications occur at a later time. Should immediate medical care be needed, subjects will be seen by Emergency Room physicians.
While there will be no direct benefit to the participants in this study, information may be gained about the existence and possible location of the gene or genes that may interact with environmental carcinogens to increase the risk of lung cancer or other smoking associated cancers. If linkage for a marker and one of these disorders can be found, it would be a major step in identifying markers that may predispose individuals at risk for developing these cancers. In the event such a linkage is identified, these individuals will be contacted for appropriate counseling.
IRB Review:
Type of Review: Expedited
Most Recent Approval: October 31, 1995
IRB Approval Number: 96-362
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
As per the subcontract between Medical College of Ohio and St. Mary's Hospital and Medical Center, St. Mary's intends to pay Medical College of Ohio to generate a minimum of 5 and a maximum of 10 pedigrees for lung cancer susceptibility families and to collect tissues and/or blood samples from members of these families. Environmental exposure data as outlined in the Risk Factor Questionnaire in the appendix will also be obtained from these families. The tissue samples will be sent to St. Mary's Hospital for DNA isolation and subsequent genotyping of the DNA as described in the Experimental Design and Methods section. The lung cancer susceptibility families from Ohio will help us address the question of genetic heterogeneity in lung cancer. They will follow the same objectives, methods, and involvement of human subjects as outlined in the abstract for the "Identification of Human Lung Cancer Susceptibility Genes" project."