We propose to conduct a genetic-epidemiologic study of familial colorectal cancer. Probands with colorectal cancer will be ascertained from population-based cancer registries in Imperial, Orange, and San Diego counties in Southern California. Based on family history information available in the registry, we will identify and recruit approximately 130 families that report a history of at least three cases of colorectal cancer in two generations. More detailed pedigree information will be obtained via a telephone interview. From these families, we will identify 80 multiple-case families that are judged to be potentially the most informative for linkage analyses, based on a simulated lod score criterion (using SIMLINK). Each member of these linkage-informative families will be asked to provide one sample of blood for DNA analyses and to complete questionnaires on risk factors for colorectal cancer. Efforts will be made to verify all reported cancers and all causes of death. For cases with colorectal cancer or any other cancer, we will obtain pathology reports and tumor blocks. Our objectives are to 1) identify the familial colon cancer (FCC) gene on chromosome 2; 2) study the effects of other putative risk factors for colon cancer, including diet, physical activity, nonsteroidal anti-inflammatory drugs, and hormones; 3) study gene- environment interactions, with a focus on factors that affect the expression or penetrance of the FCC gene; and 4) define sources of heterogeneity (i.e., what variables discriminate between families that do or do not involve the FCC gene). The primary analytical technique is linkage analysis that incorporates information on environmental covariates. In linked families, informative recombinants for fine mapping of the FCC locus will be identified. In unlinked families we will look for alternative pathways. This proposed study is Project 1. Project 2 focuses on gene-environment interactions in colorectal polyps. Project 3 focuses on the molecular genetics of colorectal polyps and cancer. The molecular work for this study will be conducted as a part of Project 3.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA063706-05
Application #
2712693
Study Section
Special Emphasis Panel (SRC (70))
Program Officer
Seminara, Daniela
Project Start
1994-08-01
Project End
1999-11-30
Budget Start
1998-06-01
Budget End
1999-11-30
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
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Zell, Jason A; McEligot, Archana J; Ziogas, Argyrios et al. (2007) Differential effects of wine consumption on colorectal cancer outcomes based on family history of the disease. Nutr Cancer 59:36-45
Zell, Jason A; Ignatenko, Natalia A; Yerushalmi, Hagit F et al. (2007) Risk and risk reduction involving arginine intake and meat consumption in colorectal tumorigenesis and survival. Int J Cancer 120:459-68
Peel, D J; Ziogas, A; Fox, E A et al. (2000) Characterization of hereditary nonpolyposis colorectal cancer families from a population-based series of cases. J Natl Cancer Inst 92:1517-22
Anton-Culver, H (1995) Cancer prevention strategies: use of cancer prevention research registries. Environ Health Perspect 103 Suppl 8:237-9