) The proposed 5-year Preventive Oncology Research Award (K07) involves three projects using existing data sets to facilitate rapid training in genetic epidemiology. Emphasis is on cancer susceptibility genes and gene environment interactions. The training and experience gained from the proposed research will enable the principal investigator to pursue a long-term career based on gene-environment interactions, in particular ionizing radiation exposure. The first project focuses on familial aggregation of hematologic neoplasms and uses personal and family history of cancer from more than 200 cases (and 200 controls) in an ongoing case-control study of cancer among Ukrainians exposed to Chernobyl radiation. A unique aspect of this study is that cancer cases and their pair-matched controls are being ascertained from two large regions with and without exposure to radiation. As such, there is great interest to test for increased risk of leukemia among exposed and non-exposed first- and second-degree relatives of exposed and non-exposed probands. The second project uses personal and family history of cancer obtained from more than 300 Ashkenasics who were recently screened for BRCA1 and BRCA2 mutations. Among the 300 screened individuals, more than 70 families with significant history of breast-ovarian cancer have been identified. Using these data, the first aim is to confirm an autosomal dominant mode of inheritance of breast ovarian cancer.
The second aim i s to determine if colon or lung cancer aggregates within this population, and if so, to perform segregation analysis to determine the mode of inheritance. Mutation analysis at the adenomatous polyposis coli (APC) susceptibility gene is being planned and could be used for penetrance calculations. The third project addresses linkage analysis with genotype data from 5 families with 25 individuals affected with Peutz-Jeghers syndrome. Two-point lod scores will be generated with fixed recombination fractions using genotype information for 11 polymorphic microsatellite markers on chromosome 19p. Didactic coursework will focus on genetics and human disease, molecular and cellular genetics, genetic epidemiology, statistical genetics, human DNA variation, recombinant DNA technology, and population genetics. Results of this training will thrust the trainee into a productive career in genetic epidemiology with a particular focus on gene-environment interactions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07CA078199-04
Application #
6376785
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
1998-07-01
Project End
2003-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
4
Fiscal Year
2001
Total Cost
$90,685
Indirect Cost
Name
Baylor College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Peterson, Leif E (2003) Partitioning large-sample microarray-based gene expression profiles using principal components analysis. Comput Methods Programs Biomed 70:107-19
Sepulveda, A R; Tao, H; Carloni, E et al. (2002) Screening of gene expression profiles in gastric epithelial cells induced by Helicobacter pylori using microarray analysis. Aliment Pharmacol Ther 16 Suppl 2:145-57
Sepulveda, A; Peterson, Leif E; Shelton, Joseph et al. (2002) Histological patterns of gastritis in H. pylori-infected individuals with a family history of gastric cancer. Am J Gastroenterol 97:1365-70
Peterson, Leif E (2002) CLUSFAVOR 5.0: hierarchical cluster and principal-component analysis of microarray-based transcriptional profiles. Genome Biol 3:SOFTWARE0002
Peterson, Leif E (2002) Factor analysis of cluster-specific gene expression levels from cDNA microarrays. Comput Methods Programs Biomed 69:179-88
Plon, S E; Peterson, L E; Friedman, L C et al. (2000) Mammography behavior after receiving a negative BRCA1 mutation test result in the Ashkenazim: a community-based study. Genet Med 2:307-11
Peterson, L E; Barnholtz, J S; Page, G P et al. (1999) A genome-wide search for susceptibility genes linked to alcohol dependence. Genet Epidemiol 17 Suppl 1:S295-300