Dr. Martha L. Slattery, Ph.D.

Professor, Division of Clinical Epidemiology

Title: DIET, ACTIVITY, AND REPRODUCTION AS RISKS FOR CANCER - NIH National Cancer Institute

We propose to expand our study of large bowel cancer by obtaining environmental and genetic data from individuals with rectal and rectosigmoid junction tumors. The original proposal was to evaluate interactions between environmental exposures; we expand this to look at environmental exposures with genetic susceptibility. Thus, this revised application is further focused on associations which have not previously been assessed with rectal cancer (energy balance) or those which appear to be associated with more distal tumors (mutagen index, smoking, alcohol, and dietary factors associated with DNA methylation). To obtain a better understanding of the significance of these environmental exposures which appear to be associated with more distal tumors, we propose to assess genetic factors which may alter susceptibility to rectal cancer. We propose to study interactions between dietary factors association with DNA methylation and the methylenetetrahydrofolate reductase gene; smoking and alcohol in combination with GST null and cytochrome p450 IA1 polymorphisms, and NAT2 polymorphisms with meat consumption and mutagen index. The rationale for these interactions is based on the literature and preliminary data from approximately 300 people from the colon cancer study. It is a goal of this study to determine heterogeneity between tumor sites in the large bowel in terms of environmental exposures. We will use the same methods developed and implemented in our original study of colon cancer (CA48998). Environmental data will be obtained from 1200 cases and 1200 population-Blood will be drawn by interviewers/phlebotomists at the time of the interview. Genetic analyses will be conducted at the University of Utah. Data analysis will focus on independent and interactive effects of environmental factors; the interaction between inherited genetic factors and environmental exposures; and genetic alterations with each other. Using polychotomous logistic regression and case-case analysis we will estimate the heterogeneity between proximal, distal, and rectal cancers in terms of environmental exposures.

Principal Investigator:

• Martha L. Slattery, Ph.D.
Marty.Slattery@hsc.utah.edu

Administration:

      • Tricia Sweeney
         Tricia.Sweeney@hsc.utah.edu
      • Nefi Aquilar
         Nefi.Aguilar@hsc.utah.edu