HuGENet™ Case Study
Genomics and Cancer Prevention Objectives
Dr. Robert Millikan
Center for Genomics and Public Health
University of North Carolina at Chapel Hill
Martinez E, et al. Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene. Proc Natl Acad Sci 100: 7859-64 (2003).
The aims of this learning module are:
- To learn about gene discovery and biologic function of genes.
- To learn about Hardy Weinberg equilibrium and how it can be used as a quality control check.
- To illustrate how multiplicative interactions can be characterized when a genetic and environmental factor act at different points in a multi-step biologic pathway.
- To discuss the public health implications of gene-environment interaction.
This learning module is aimed primarily at epidemiologists but could be adapted for discussion among public health professionals.
Regular use of aspirin and other non-steroidal anti-inflammatory drugs reduces polyp recurrence and lowers the risk of colon cancer. But how do these drugs work? And who benefits from taking them? Does everyone benefit equally? A recent paper by Martinez et al. sheds light on these questions, and provides fascinating insight into how genetic polymorphisms can help to uncover biologic mechanisms and establish benefit of public health interventions. The authors provide evidence that the reduction in risk of polyp recurrence derived from taking aspirin may be greater in persons with a common variant in the ornithine decarboxylase gene (ODC). The ODC gene is a key enzyme involved in the biosynthesis of polyamines. And aspirin use is involved in the breakdown of polyamines. Thus, the ODC gene and aspirin use target a common metabolic pathway. The variant in the ODC gene influences how many polyamines are made, and aspirin influences how quickly polyamines are broken down. Since the ODC polymorphism and aspirin use act via different mechanisms on the same metabolic pathway, the effects may be synergistic. This article presents a complex but very illustrative example of SNP discovery, functional genomics, and association studies. It raises important issues about the use of genetic information in public health practice. A series of questions are posed, followed by some suggested answers.
This case study assumes that the reader has studied the article by Martinez M E, O'Brien TG, Fultz KE et al. Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene. Proc Natl Acad Sci USA. 2003 Jun 24;100(13):7859-64 (Full Text)
Martinez E, et al. Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene. Proc Natl Acad Sci 100: 7859-64 (2003). PubMed abstract