Centers & Programs News

Genetics and Disease

The role genes play

Genetics is one of the hottest buzzwords in medicine today. With technologies in place to explore the fundamental building blocks of life, enormous resources are currently being devoted to investigating the genetic basis of diseases, developing gene-based tests to predict how people will respond to therapies, and, looking to the future, using genetic information to help determine individualized courses of therapy based on genetic predilections—and maybe even manipulating the genes themselves to prevent or reverse disease.

But just what is known so far about genes, and how well can this information be used to treat disease now?

According to Wendy Chung, MD, PhD, Director of Clinical Genetics, NewYork-Presbyterian Hospital/Columbia, much is known about so-called 'single-gene disorders.' Of the 25,000 to 30,000 genes in the human body, over 5200 genes have been identified as causing specific diseases. These powerful connections include Down syndrome, cystic fibrosis, certain types of breast cancer, certain congenital heart conditions, and others in which an aberrant or mutant single gene will very likely lead to a particular condition.

Clinical programs are in place at NewYork-Presbyterian Hospital/Columbia to screen patients for all of these conditions, such as BRCA1 and BRCA2 genes for breast cancer, and specific markers for pancreatic cancer, hereditary non-polyposis colon cancer syndrome (HNPCC), and other conditions for which genetic causes have been pinpointed.

Human Chromosomes

Such programs are particularly effective in treating diseases for which a single gene confers high risk, and early treatment can often prevent or reduce the impact of the disease. It is known that women with BRCA1 and BRCA2 mutations may face up to a 75% risk of developing breast cancer in their lifetime, and that early screening and intervention saves lives. The presence of certain genetic markers, such as whether the cancer is estrogen receptor positive or negative, further guides the treatment of patients with breast cancer for even better results.

Aggregation of Genes

Microarrays, also called gene chips, provide snapshots of all the genes that are active in a cell at a particular time.

While the genetic basis of breast cancer is in no way simple, the role of genes in many other conditions remains even more elusive. Many diseases are known to have a familial basis, meaning that they run in families, but they likely result from a combination of genetic aberrations, environmental exposure, and lifestyle issues, rather than from a single gene mutation. In such cases, multiple genes may contribute to increasing a person's risk for a particular disease. These complexities represent a vast and largely untapped area of exploration.

"The new frontier is how to identify common genetic susceptibilities to disease, in which the presence of multiple abnormal genes may together contribute to the development of a disease," says Dr. Chung. "The challenge ahead is to identify the composite risk of multiple contributions to diseases," she explains. Whereas the identification of single gene disorders may be considered the first phase in understanding genes, the second phase will involve learning how multiple genes act together to increase people's risk for diseases. At this time, researchers have identified approximately 300 genes that, in conjunction with other factors, are linked to common diseases.

Dr. Chung suspects that most common diseases may fall into this category. At the edge of this very complex frontier, researchers such as Dr. Chung are making early inroads. Scientists have identified the genetic contributions of four genes in causing macular degeneration, the most common cause of blindness in the elderly. Armed with this understanding, they can now more accurately predict who will go blind. The hope is to be able to use this knowledge to develop targeted therapies in the future. The researchers also know there is a link between macular degeneration and inflammation; moreover, they have begun to understand the importance of inflammation in heart disease, diabetes, and other conditions, and they have preliminary leads from genetic research about what might be the genetic culprits—but the full causes and mechanisms still remain far from clear.

Even more difficult, says Dr. Chung, is understanding the complex dance between genetics and the environment. "This is incredibly important," she says. While genes cannot be altered at this time, we can modify other risk factors (such as diet, smoking, exercise, etc.) in an effort to prevent or treat disease."

Gene therapy, which involves manipulation or replacement of faulty genes with different or healthy genes, may some day offer hope for curing genetic illnesses. Although some promising results have been achieved in research to date, gene therapy is still in its early infancy. According to Dr. Chung, the first widespread clinical applications of gene therapy will likely be as a method of drug delivery, such as targeting therapeutic proteins to cancerous tissues to kill the tumor or repair heart tissue after a heart attack.

In the meantime, genetic counseling is a vital component of each of NewYork-Presbyterian/Columbia's centers of excellence. Through testing, education, and evaluation of treatment options, patients and family members of those with inherited diseases can significantly improve their likelihood of preempting those diseases.