The development of laboratory methods to detect persons with a genetic susceptibility to breast cancer could aid in the determination of genetic and environmental interactions which result in disease and the development of preventive measures. This study tests whether variations in peripheral lymphocyte mutagen sensitivity, as determined by cytogenetic analysis, are associated with the diagnosis of breast cancer or the elevated breast cancer risk of women with atypical hyperplasia and a family history of breast cancer. Lymphocyte cultures from 20 newly diagnosed untreated patients with invasive breast cancer, 40 high risk breast cancer risk women and 40 control subjects will be established and the cells treated with a battery of mutagens with widely different mechanisms of action. The resultant cytogenetic damage will be assessed using both conventional chromosomal aberration studies and the analysis of sister chromatid exchange (SCEs). The use of a battery of mutagens and multiple endpoints of cytogenetic damage increases the power of the study to detect associations of breast cancer risk and mutagen sensitivity. The concurrent study of high breast cancer risk individuals and women with frank cancer will further indicate the extent to which these measurements of mutagen sensitivity are affected by neoplasia.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA043764-02
Application #
3186092
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1986-12-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Wiencke, J K; Wara, D W; Little, J B et al. (1992) Heterogeneity in the clastogenic response to X-rays in lymphocytes from ataxia-telangiectasia heterozygotes and controls. Cancer Causes Control 3:237-45
Kelsey, K T; Christiani, D C; Wiencke, J K (1991) Bimodal distribution of sensitivity to SCE induction by diepoxybutane in human lymphocytes. II. Relationship to baseline SCE frequency. Mutat Res 248:27-33
Wiencke, J K; Christiani, D C; Kelsey, K T (1991) Bimodal distribution of sensitivity to SCE induction by diepoxybutane in human lymphocytes. I. Correlation with chromosomal aberrations. Mutat Res 248:17-26
Wiencke, J K; Kelsey, K T; Lamela, R A et al. (1990) Human glutathione S-transferase deficiency as a marker of susceptibility to epoxide-induced cytogenetic damage. Cancer Res 50:1585-90
Wiencke, J K; Kelsey, K T; Lamela, R A et al. (1990) Genetic polymorphisms in carcinogen metabolism predict substrate-induced cytogenetic damage in humans. Prog Clin Biol Res 340B:137-47
Wiencke, J K; McDowell, M L; Bodell, W J (1990) Molecular dosimetry of DNA adducts and sister chromatid exchanges in human lymphocytes treated with benzo[a]pyrene. Carcinogenesis 11:1497-502
Kelsey, K T; Wiencke, J K; Little, F F et al. (1989) Sister chromatid exchange in painters recently exposed to solvents. Environ Res 50:248-55
Kelsey, K T; Wiencke, J K; Eisen, E A et al. (1989) Sister chromatid exchange in chronic ethylene oxide-exposed primates: unexpected effects of in vitro culture duration, incubation temperature, and serum supplementation. Cancer Res 49:1727-31
Kelsey, K T; Wiencke, J K; Eisen, E A et al. (1988) Persistently elevated sister chromatid exchanges in ethylene oxide-exposed primates: the role of a subpopulation of high frequency cells. Cancer Res 48:5045-50