A health-conscious way to celebrate turning 50 is to drink a gallon of a salty, citrusy-tasting electrolyte solution, then find yourself a couple of rolls of toilet paper and wait for its effect. All that sitting around is a good time to think about your first 50 years, and what you might want to do with the second. The next day it's off to the doctor's office to have your innards probed with a colonoscope. Your bowels are inflated with air; your brain is numbed with sedatives. Happy birthday. Happy, happy birthday.

OK, so a colonoscopy is really no party at all, but it is serious business. Colorectal cancer is the second most common cause of cancer death in this country, and yet more than half of U.S. adults over age 50 have not been screened for it. Colonoscopy remains the gold standard for screening, but checking the stool for microscopic, invisible traces of blood – fecal occult blood testing – remains the simplest screening measure. A small smear of stool is wiped onto a card, and the card is treated with a chemical. If there is blood in the sample, the card turns blue.

A study headed by Dr. David Ahlquist at the Mayo Clinic and recently published in the Annals of Internal Medicine put conventional fecal occult blood testing up against a relatively new technology that detects tiny fragments of abnormal DNA in the stool.

Specimens checked for specific genes
From 2001 through 2007, several thousand volunteers from all across the country express- shipped to Rochester an intact stool specimen in an insulated container packed with ice. (I live near the airport; I can admit to now thinking more about what it is that's flying over my head.) There the specimen was frozen to minus 80 degrees Celsius and sent with dry ice to Massachusetts, where a company called EXACT Sciences biochemically sifted through each specimen looking for specific DNA sequences called point mutations. These genes – K-ras,   APC, p-53, BAT-26 – are known to be important in the development of colon cancer. The cells that line the GI tract grow and die and are shed at a very high rate, so a normal stool contains lots of cell debris, including DNA.

Generally speaking, the development of colon cancer is a very slow process. Colon cancer typically develops as a small knuckle of tissue called a polyp. The cells that make up a polyp in its early stage don't look very abnormal, but as these cells continue to divide and grow (and the polyp grows in size), each generation becomes more bizarre and twisted, moving into a distorted "premalignant" phase. With more time – typically 5 to 10 years – the cells that make up the polyp can grow to become fully malignant.

The goal of colon cancer screening and colonoscopy is to detect and remove precancerous or cancerous polyps early, before they grow down the stalk of the polyp and into the colon wall, or spread out into the body. Snaring and removing a polyp during colonoscopy can be a very simple solution compared to what could become a very serious and potentially deadly problem.

One of the main problems with fecal occult blood testing is that it can be too little, too late. Most young polyps don't bleed, or they bleed very intermittently, so the test tends to detect only larger polyps that are in later phases of cancerous growth. This is probably why, as in Ahlquist's study, fecal occult blood testing detected only 20 percent of cancerous lesions. In his study, testing for blood in the stool missed the large majority of premalignant adenomas greater than 1 centimeter. The article points to this as a plausible explanation for why stool blood screening has been shown to have either modest or negligible effects on the incidence of colon cancer in this country: They miss a lot.

One DNA group did much better
How did Ahlquist et al's stool DNA testing perform? In this study, two different groups of DNA testing were performed on each sample, and the first actually underperformed the standard stool blood tests. The second DNA panel tested for a different set of mutations and did much better. In fact, it was twice as powerful in detecting cancerous lesions compared to standard fecal occult blood testing.

There may come a day when Hallmark develops a "You're 50! The Big Five-O!" card, where, after the party dies down, you can smear a little sample on to the special paper imbedded in the cloak of the Grim Reaper caricature that pops up from inside the card.  Then slide the card into the preaddressed envelope and express mail it in for K-ras, APC, p-53, etc., tumor gene evaluation.

That day has yet to arrive. The technology is complex. But the work of Ahlquist and others points out how medicine is going "micro," and how modern biochemical techniques might allow us to be much more specific about who needs a colonoscopy and who doesn't.