The molecular biological evolution and genetics revolution

Like the Internet revolution, the molecular biological evolution and the genetics revolution will sweep us off our feet. Understanding how this development will affect gastroenterology is paramount to becoming the best doctor in the 21st century. Let’s examine this phenomenon further.

Past effect. Compare the medical journals of today with those of a couple of decades ago. Gone are the days of just clinical studies; instead, you will notice more and more peer-reviewed studies are based on molecular biological and genetic finding. As a practicing gastroenterologist, you have to be able to interpret and put to practical use the pertinent molecular and genetic-based findings. An example: A few years back, hemochromatosis diagnosis and screening of first-degree relatives were based solely on ferritin, transferring saturation, iron studies and liver biopsy with iron index.

In 1996, Feder et al. discovered that a gene mutation of hemochromatosis, HFE, existed; the predominant genotypes were identified as HG3D/C282Y heterozygote and C282Y homozygote. Today, ordering genetic testing for hemochromatosis genotypes is an integral part of the dianogis and screening of first-degree relatives. With this genetic testing, we can monitor patients more judiciously and treat them before they manifest symptoms of hemochromatosis.

Current effect. Today, major medical journals are filled with "Star Wars" – like words that can be confusing: TNF, MLH1, COX-2, C-MYC, and p53. How do we make sense of this alphabet soup? For many practicing gastroenterologists, this is like a whole new language! However, knowledge of this language is extraordinarily important – not only to provide the best care to patients, but also because patients will often know about these terms themselves from the Internet.

Not long ago, a patient came with a stack of computer printouts of articles and abstracts and a puzzled look on her face. She said to doctor, "I am 23 years old and Jewish and my doctor told me that I am at high risk of getting colon cancer. He wants to undergo a colonoscopy. I am here for a second opinion." She then turned to the stack of articles and stated: "I am otherwise healthy, asymptomatic and have no family members with gastrointestinal cancer or polyps." Over the Internet and library and found nothing that states why I should necessarily get a colonoscopy now. All the literature says is that Ashkenazi Jewish people are more likely to have the 1130K mutation, which can increase the lifetime change of colorectal cancer. But there is nothing about every Jewish person requiring colonoscopies at this age! "Of course she was correct. Genetic testing for the 11307K mutation proved negative. Recommended that she wait until age 50 for her first colonoscopy unless other symptoms or family history developed earlier.

As many of us are learning, the adenomatous polyposis coli (APC) 11307K mutation is identified in approximately six percent of the Ashkenazi Jewish population and may confer up to a 30 percent lifetime risk of colon cancer. However, unlike other mutations in the APC gene found in familial adenomatous polyposis (FAP), this mutation does not directly cause colon cancer but behaves as a colon cancer predisposition gene. In this case, all that was necessary to provide the best care possible was to be able to translate the more difficult-to-understand literature into its appropriate clinical application.

Future effect. As a Human Genome Project reaches completion, we will finally begin to understand which people at risk for certain diseases and which novel genetic therapies will be useful to control, maintain remission of, or cure certain disease. Mysteries like the following will likely be unraveled: What are the biomarkers for progression of Barrett’s esophagus to adenocarcinoma? How can we use defensins to combat inflammatory bowel disease?

And which novel genetic-based therapies can be used to quell Wilson’s disease? How can we keep up with this revolution? How can we find those clinical pearls and understand their bases? First, we all need to follow the top medical journals and newspapers to try to identify certain new molecular biological and genetic-based studies. Second, we need appropriate continuing medical education. CME programs and those presented at Digestive Disease Week and the American College of Gastroenterology’s meetings to create a section for "Clinically relevant Translational Research."

Updates on what is vital to practicing gastroenterologists, reviewed by a physician who can communicate those ideas in terms the practicing gastroenterologist can easily understand, are required. With all the new information derived from this revolution, being a practicing gastroenterologist in the 21st century will be more challenging than ever. We all try to keep up todate with new information in order to be the patient’s best advocate.