Abstract

The long-term objective is to determine whether exposure to different exogenous mutagens are responsible for differences in the incidence and prognosis of breast cancer in ethnically and racially diverse populations. The approach is to compare the specific biochemical pattern of mutation in the tumor suppressor gene, p53, in breast cancers from populations with low incidence of breast cancer, Japanese and native Americans, to the pattern of mutation in populations with a high incidence of breast cancer, northern Europeans and North Americans. Ethnically diverse groups within North America including a midwestern Caucasian and midwestern Black population will also be compared. Methodology has been developed which permits direct sequencing of most of the p53 genome from pure clusters of cancer cells isolated from touch preparations of fresh or frozen tissue. This technology makes a molecular epidemiological approach to human breast cancer feasible because it can be applied to unselected tumor specimens and does not significantly compromise use of the same sample for other purposes. Precise definitions of patterns of mutation in populations at high and low risk for breast cancer may help to distinguish between endogenous and exogenous processes contributing to the development of this cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA056881-03
Application #
2097663
Study Section
Pathology B Study Section (PTHB)
Project Start
1992-08-05
Project End
1997-07-31
Budget Start
1994-09-01
Budget End
1995-05-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
City of Hope National Medical Center
Department
Type
DUNS #
City
Duarte
State
CA
Country
United States
Zip Code
91010

  Publications

Buzin, C H; Tang, S H; Cunningham, J M et al. (2001) Low frequency of p53 gene mutations in breast cancers of Japanese-American women. Nutr Cancer 39:72-7
Blaszyk, H; Hartmann, A; Cunningham, J M et al. (2000) A prospective trial of midwest breast cancer patients: a p53 gene mutation is the most important predictor of adverse outcome. Int J Cancer 89:32-8
Hartmann, A; Blaszyk, H; Kovach, J S et al. (1997) The molecular epidemiology of p53 gene mutations in human breast cancer. Trends Genet 13:27-33
Hartmann, A; Blaszyk, H; Saitoh, S et al. (1996) High frequency of p53 gene mutations in primary breast cancers in Japanese women, a low-incidence population. Br J Cancer 73:896-901
Kovach, J S; Hartmann, A; Blaszyk, H et al. (1996) Mutation detection by highly sensitive methods indicates that p53 gene mutations in breast cancer can have important prognostic value. Proc Natl Acad Sci U S A 93:1093-6
Blaszyk, H; Hartmann, A; Tamura, Y et al. (1996) Molecular epidemiology of breast cancers in northern and southern Japan: the frequency, clustering, and patterns of p53 gene mutations differ among these two low-risk populations. Oncogene 13:2159-66
Hartmann, A; Blaszyk, H; McGovern, R M et al. (1995) p53 gene mutations inside and outside of exons 5-8: the patterns differ in breast and other cancers. Oncogene 10:681-8
Hartmann, A; Rosanelli, G; Blaszyk, H et al. (1995) Novel pattern of P53 mutation in breast cancers from Austrian women. J Clin Invest 95:686-9
Blaszyk, H; Hartmann, A; Schroeder, J J et al. (1995) Rapid and efficient screening for p53 gene mutations by dideoxy fingerprinting. Biotechniques 18:256-60
Saitoh, S; Cunningham, J; De Vries, E M et al. (1994) p53 gene mutations in breast cancers in midwestern US women: null as well as missense-type mutations are associated with poor prognosis. Oncogene 9:2869-75

Showing the most recent 10 out of 12 publications