Ever wonder why some people can quit smoking while others try repeatedly without success?  The answer may be related to your genetic makeup. Studies have shown that 70 percent of smokers want to quit, but only three percent are successful each year. That’s according to Rachel Tyndale, Ph.D., professor of Pharmacology and Psychiatry, Centre for Addiction and Mental Health at University of Toronto. Her research has some fascinating new evidence that could lead to individualized therapies that will help those who struggle to kick the habit.

Dr. Tyndale and her research team have uncovered genetic mutations linked to smoking behavior. They have taken this information a step further by conducting pharmacogenomics studies to identify how these genetic mutations impact the way a person responds to different smoking cessation treatments.

For example, people with the CYP2A6 genetic variant that metabolizes – or processes – nicotine from a cigarette slowly:

• Have a lower risk of being an adult smoker
• Smoke fewer cigarettes and have a lower risk of dependence
• Have a lower risk of tobacco-related diseases, such as lung cancer, COPD, diabetes and obesity
• Have an increased chance of successfully stopping smoking on their own or using a nicotine patch to slowly wean themselves off the drug

On the other hand, research shows people with another genetic variant who process nicotine faster are much more dependent on smoking. They tend to smoke more often and are at higher risk for developing tobacco-related diseases. In addition, these smokers do not benefit from the patch, but do respond to other medications.

Dr. Tyndale emphasized that while pharmacogenomics testing is not widely used clinically to help smokers who want to quit, this approach holds promise in helping identify new therapies that are shaped to how an individual processes medications.

Desperate for answers – improving diagnosis of rare diseases

Some patients and their families search for years for answers to unexplained, often debilitating symptoms. William Gahl, M.D., Ph.D. and his research team meet with these patients, hoping to find a diagnosis for their rare disorders. Dr. Ghal is clinical director of the National Institutes of Health (NIH) Undiagnosed Diseases Program, which sees 1,100 patients per year. Forty percent of these patients are children and half of the patients have neurological disorders.

Dr. Gahl and his team have played a significant role in advancing medical knowledge about both rare and common diseases. Many of the disease pathways uncovered when diagnosing rare disorders can be seen in more common conditions.

“The greatest satisfaction is when we can provide a diagnosis to patients and their families – even if there is no treatment, a diagnosis can bring great relief,” says Dr. Gahl.

The program’s multidisciplinary team has been critical to their success.

“We can accomplish in one week what might take a year in clinical practice,” says Dr. Gahl.

After establishing the Undiagnosed Disease Program in 2008, NIH extended the program’s reach by establishing the Undiagnosed Disease Network in 2012. The network includes seven centers throughout the United States.

Because of the great need, NIH collaborated with the Wilhelm Foundation in Sweden in 2015 to expand research into rare diseases by creating the Undiagnosed Disease Network International. Researchers from Mayo Clinic Center for Individualized Medicine are participating in this international effort to collaborate and share data on rare diseases in order to solve more unexplained medical cases.

Liquid biopsies for cancer screening and treatment: a panel discussion

The afternoon session concluded with a panel discussion about the exciting field of research surrounding liquid biopsies, including cell-free DNA tests and tests designed to detect circulating tumor cells in the blood stream. The panel included:

• Minetta Liu, M.D., associate professor of Oncology, Mayo Clinic
• Muhammed Murtaza, M.B.B.S., Ph.D., assistant professor of Medicine, Mayo Clinic, and co-director of the Center for Noninvasive Diagnostics at TGen
• Richard Williams, MB.B.S., Ph.D., medical director at GRAIL, Inc.

While these tests are currently being used to identify specific genetic mutations in advanced cancer, they have great potential in the future to be used in the full range of cancer care, including screening for early cancer detection, monitoring of cancer growth and recurrence, identification of targets for therapy and measuring treatment response.

Advantages of the tests highlighted during the discussion include the ability to:

• Obtain a more accurate picture of cancer activity
• Find cancer earlier, before it appears on an imaging study
• Perform a less invasive test, posing fewer risks
• Lower cost and reduce turnaround time for results
• Potentially replace or complement traditional screening methods, such as tissue biopsy or imaging studies
• Increase access to cancer screening and monitoring to more patients, especially those who do not have access to a large medical center

Panelists agreed that in order to bring this promising new testing method into clinical practice, researchers need to collaborate in large-scale clinical studies to verify the value of these tests and develop guidelines to bring them into clinical practice.

Keep the conversations going

For a wrap up and summary of  news related to the conference and the Mayo Clinic Center for Individualized Medicine, visit our blog, Facebook, LinkedIn or Twitter at @MayoClinicCIM and use the hashtag #CIMCon17.

The Mayo Clinic Center for Individualized Medicine is hosting the conference with support from the Jackson Family Foundation.

Don’t forget to save the date for #CIMCon18, which will be held Sept. 12-13, 2018.

Tags: #cell-free DNA testing, #Dr. Minetta Liu, #Dr. Muhammed Murtaza, #Dr. Rachel Tyndale, #Dr. Richard Williams, #Dr. William Gahl, #liquid biopsies, #pharmacogenomics testing, #rare diseases, #rare genetic disorders, #smoking cessation, #Undiagnosed Disease Network, #Undiagnosed Diseases Network International, #Unidagnosed Disease Program, National Institutes of Health, Precision Medicine