James E. Cantrell, MD
“Most physicians aren’t aware of how common the problem is,” says James E. Cantrell, MD, an oncologist with Birmingham Hematology and Oncology.
Globally about 850,000 people get colorectal cancers a year with about five percent of those stemming from a hereditary cause. “That five percent could be detected before the patient gets cancer. So that’s about 40,000 people worldwide, and about 7,000 a year in the U.S.,” Cantrell says.
Only in the last year or so has the option for genetic testing become accessible enough to warrant popular consideration. “You used to have to send a specimen to California and wait six weeks for results. But now the lab science has become commercially available,” Cantrell says.
“It’s a sadly neglected area for screening,” Cantrell says. “Anyone with colon cancer should get the test. If they detect that a colon cancer patient has the inherited mutation, then screen all of their first-degree relatives — siblings, parents, children — and any relative who has colon cancer.”
Should a family member test positive for the mutation, “they have a serious problem,” Cantrell says. “They have a greater than fifty percent chance of getting colon cancer, and other cancers. Once you identify a mutation, than half of their offspring will have the mutation too.”
Those found with the hereditary mutation for colon cancer need to undergo intensive regular screening moving forward. “They need colonoscopies often and very young,” Cantrell says. “Typically if they have Lynch syndrome, which is the most common cause, they need to start screening at 20 to 25 years of age and do it every one to two years. Or start ten years before the youngest case was identified in the family.”
The mutation for the hereditary colon cancer also triggers risks for other types of cancers, including a 40 percent increased chance for uterine cancer. “There are three or four other cancers at higher risk too, and the extent of risk varies,” Cantrell says. “The main thing is to identify the gene and then refer them to a genetic counselor, because it becomes complex after that.”
Of the estimated 7,000 cases in the U.S. from the hereditary mutation, 80 percent are missed for lack of gene testing. “So unless the patient comes in and says ‘I have two brothers with colon cancer and my mom had uterine cancer,’ we’re not focusing on getting these tests,” Cantrell says.
Cantrell uses the PREMM model from the Dana-Farber Cancer Institute for predicting the risk of hereditary colon cancer. “But the Bethesda criteria would be the one most found in medical textbooks. The PREMM is better for Lynch syndrome, and that’s primarily what it’s used for, where Bethesda is basically more about sensitivity and less specificity,” Cantrell says.
Physicians can freely access the PREMM criteria at http://dana-farber.prod.dfcidev.org/pat/cancer/gastrointestinal/crc-calculator/default.asp. “It scores the patient for you online. But you have to put in more variables about the patient than with Bethesda, and it’s pretty lengthy, including second-degree relatives,” Cantrell says.
According to the Bethesda model, physicians should look for any of these seven criteria:
- Two hereditary colon cancers in first-degree relatives, including colorectal or extra colonic cancers associated with colon cancers
- Colorectal cancer in themselves and a first-degree relative
- Extra colonic cancer before age 45 and/or colorectal adenoma before 40
- Colorectal or endometrial cancer before age 45
- Right-sided colorectal cancer before age 45 with an undifferentiated pattern
- Signet-ring type colorectal cancer before age 45
- Adenoma before age 40.
“You fill out this information for the company that makes the test, and they’ll score it,” Cantrell says. Blue Cross of Alabama covers the test if the patient meets a certain score of these criteria. “It’s pretty good criterion, because they’d like to do the testing, but it has to be a reasonable level for specificity.”
Cantrell warns physicians that most patients who match one of these criteria don’t have hereditary colon cancer. “The criteria are set at a pretty high level of sensitivity, so it doesn’t necessarily mean a high probability. We want to set the threshold pretty low to trigger one to do the testing, and then we’re not going to miss as many.”
Cantrell says the lists of criteria can be confusing. “You can fall asleep in the middle of these lists, and you may only see a case of this once every two years,” he says. “But the point to the general physician is how often you are asking these things. The whole idea is to raise your level of awareness, so you’ll order the test. This is a big deal, and it can save a lot lives.”