It may be an indelicate subject to bring up at the dinner table, but colon cancer screening based on fecal matter merits discussion. The first-generation kit ColoGuard rolled out in August 2014, and now an advanced version, ColoGuard Plus, has received FDA approval. October 2024. What’s new?Â
Journey from food to poop. Be it eggs, English muffin, or oatmeal with berries for breakfast, tuna salad or General Tsao’s chicken for lunch and burgundy potato-carrot-beef stew for supper, it all ends up as mushy chyme in our stomach. The next stop is the small intestine where assorted digestive enzymes break the food down and allow 95% of nutrients to be absorbed into the blood stream. The remaining 5%, mostly fiber, heads down the road to the large intestine (colon) where water is removed and food remnants solidify into fecal matter.
sDNA in fecal matter. What’s in a healthy person’s poop? Besides water, fecal matter consists of undigested fiber, fats, cholesterol, and bacteria. However, there is also something else in the fecal matter from an individual with colon cancer or pre-cancerous polyps. Tumor DNA! It turns out that colon tumors, benign or malignant, shed DNA into the stool stream, labelled as sDNA. This can be extracted, amplified, and analyzed for colon cancer genes. ColoGuard identifies 11 genes whereas ColoGuard Plus zooms in on only 4 genes but has greater sensitivity (detection of active colon cancer, also called a “true positives”) and improved specificity (absence of colon cancer or “true negatives”). In a large clinical trial, ColoGuard Plus demonstrated 92% sensitivity and 43% specificity, a marked improvement compared to the previous °ä´Ç±ô´ÇłŇłÜ˛ą°ů»ĺĚýkit. The 4-gene cluster out-performed the 11-gene panel. Less is more! How come?Â
Tiny methyl group makes a big difference. The secret to the better performance by ColoGuard Plus is embedded in DNA methylation: All four biomarkers are genes associated with altered DNA methylation commonly found in colon cancer. A molecule is said to have undergone methylation after a methyl group (CH3) has been incorporated into the molecule. The consequence of methylation is gene silencing. Cancer cells make use of methylation for their survival by engaging in molecular tricks that lead to methylation of tumor suppressor genes (TSGs). That leads to the inactivation of these suppressor genes meaning that the cancer cells can grow uncontrollably. Although a universal trait in cancers, methylation biomarkers are unique for cancer type, subtype, stage, and grade. The four methylation biomarkers selected for ColoGuard Plus have apparently been well selected as shown by the improved sensitivity and specificity as described above.Â
Trust but verify. What happens when ColoGuard Plus screening test result is positive? Alarming as it must be, the result is not final and ought to be verified by the gold standard: COLONOSCOPY. The micro camera-equipped tube offers a panoramic view of the colon and allows surgical removal of pre-cancerous polyps right there and then during the procedure. As mentioned above, ColoGuard Plus kit harbors a 92% sensitivity of true positives, leaving possibly 8% false positives to be verified by colonoscopy. Despite colonoscopy’s dual role of colon cancer screening and prevention, the invasive nature of the procedure, and the uncomfortable preparation, makes many shy away. This is where the handiness of ColoGuard Plus comes in. Even though it is not totally reliable, some screening is better than no screening! “Skate to where the puck is going to be,” coined by hockey legend Wayne Gretzky, also applies to cancer. Early detection of the disease is the key to successful treatment.
Dr. Nancy Liu-Sullivan holds a Ph.D. in biology and served as a senior research scientist at Memorial Sloan Kettering Cancer Center. She currently teaches biology at the College of Staten Island, City University of New York.
