The Scenario

Roger Granger is a 24-year-old graduate student in architecture who is also a full-time draftsman. Roger's mother as well as his uncle (his mother's brother), Stan, both died of colon cancer-his mother at the very young age of 32 and his uncle at the extremely young age of 29.

Roger also remembers his mother saying that her doctor told her she had "all of these bumps" in her intestines. Roger is concerned that he may have inherited a genetic condition that causes colon cancer. To further evaluate his risk, Roger decides to fill out Genetic Health's online family medical history (FMH).

The Family Medical History

In the process of filling out his FMH, Roger phones his great aunt to ask her about the health of his grandfather—the father of Roger's mother and his Uncle Stan, whom he never knew. She reports that his grandfather also died of colon cancer, at the age of 45. She knows of no other family members who have had colon cancer. Noting the multiple affected relatives in different generations as well as the young age of diagnosis, Roger is even more concerned that he and his siblings may have inherited an increased risk for colon cancer.

The risk analysis he requests from Genetic Health confirms that his self-reported family history is strongly suggestive of inherited CRC, particularly familial adenomatous polyposis (FAP). The Genetic Health e-report recommends that he seek genetic counseling from a physician or genetic counselor to confirm his family's medical records, that he consider genetic testing, and that he receive counseling about the complex psychological implications of genetic testing. The report also recommends that Roger and his siblings begin intensive screening for CRC while they are in the process of confirming the diagnosis of FAP. Roger talks with his siblings, reads the information about CRC and FAP on the Genetic Health web site, and immediately makes an appointment with his family physician.

The colon cancer information reported in the FMH, combined with the comments of Roger's mother about her many "bumps" (which the physician assumes to be polyps), lead Roger's doctor to concur that Roger's mother, uncle, and grandfather may have had FAP.

Roger's physician gives him a physical examination, including an anoscopy, and finds no evidence of the polyps that give rise to colon cancer. Next, the physician looks in Roger's mouth for signs of the dental abnormalities—extra or missing teeth, teeth impacted under the gums, or cysts in the jaw—that are associated with FAP. Roger's physician finds no such abnormalities, nor does Roger remember having any difficulties with his teeth as a child.

Genetic Counseling

While all of the above news is good, the physician knows that Roger could still be at greater risk than most people for getting colon cancer at some point in his life. For this reason, he refers Roger to a gastroenterologist for a sigmoidoscopy (to screen for polyps and CRC), and to a genetic counselor to explore testing options.

Like Roger's physician, the genetic counselor believes it likely that Roger's family carries a genetic mutation that predisposes affected members to an eventual diagnosis of colon cancer. The next step in the genetic counselor's detective work is a thorough review of the family's medical records. The counselor explains the consent forms Roger will need to sign to facilitate this process and answers his questions. Next, the counselor obtains signed record release forms from relatives of the affected family members (Roger's mother, uncle, and grandfather), then requests and reviews their medical information as well. If any of these family members had been genetically tested, the test results would help Roger's health care providers make their diagnosis and identify which tests would be most helpful to him.

After completing her review, the genetic counselor concludes that FAP is a likely diagnosis for Roger's family, although none of Roger's relatives have undergone genetic testing. To confirm this diagnosis, the counselor recommends a flexible sigmoidoscopy and an eye exam for Roger and his siblings - the sigmoidoscopy to examine the most accessible portion of the colon for polyps, and the eye exam to look at the retina (the back of the eye) for a pigmentary abnormality that is often seen in patients with the genetic mutation that causes FAP.

This photo of a retina shows the eye abnormality associated with FAP - congentital hypertrophy of the retinal pigment epithelium, or CHRPE - that Fran's opthamologist discovered in her eye exam.

Roger's sister, Fran, agrees to the eye exam but decides to put off the CHRPE sigmoidoscopy-perhaps because the procedure, which involves inserting a tiny camera into the colon, is uncomfortable and (to some people) embarrassing. In the meantime, Roger and his brother Tommy have each had a normal sigmoidoscopy. The men's eye exams are also normal; however, Fran's is not: Her ophthalmologist finds congenital hypertrophy of the retinal pigmented epithelium, (CHRPE), the eye abnormality associated with FAP. Concerned, Fran now agrees to undergo a sigmoidoscopy, which unfortunately shows her colon to be covered with polyps.

Genetic Testing

Because Fran's sigmoidoscopy strongly suggests that she has inherited a mutation associated with FAP, the counselor believes she is the family member who is most likely to have a detectable mutation, and she now recommends genetic testing for Fran. The results confirm the counselor's suspicions: They reveal a shortened APC (adenomatous polyposis coli) protein, which indicates a mutation in the APC gene of the sort associated with FAP.

While polyps usually appear during the teenage years in individuals who have been diagnosed with FAP, Roger and Tommy, both in their early 20s, are young enough that they could still develop them in the future if they have the FAP mutation. (However, had the brothers been 35 or older with similar negative findings on their physical exams, genetic testing would be considered unnecessary.) After receiving extensive counseling, both Roger and Tommy choose to undergo testing. Happily for them, their tests are negative, and Roger and Tommy are pleased to know that their children will not be at risk for inheriting the genetic mutation.

After individual genetic counseling sessions and much discussion with other family members, Roger's cousins (Stan's children) also seek testing; two of them are found to carry the mutation as well.

Although only about 5 percent of the general population will develop colon cancer, virtually 100 percent of patients with the FAP mutation will eventually develop colon cancer if surgery is not performed to remove the colon. The genetic counselor and Fran's doctor must now help her cope with her condition and its impact on her life, including the psychological impact of knowing she is at enormous risk of developing cancer and the need to consider extensive surgery to prevent the development of cancer.

Treatment

The results of Fran's genetic testing as well as the discovery of polyps in her colon lead Fran's doctor to recommend that she undergo an immediate colectomy to prevent colon cancer. Because FAP patients are also more likely to develop rectal cancer (12 percent of FAP patients will develop this type of malignancy within 12 years of colectomy), Fran's doctor recommends that Fran have both her colon and rectum completely removed. Unfortunately for Fran, this means she must now have a permanent colostomy. Another option would be a recently developed surgical procedure called an ileal pouch procedure, in which a permanent colostomy is avoided, and instead an artificial rectum is created from a diverted piece of upper bowel. This procedure has many advantages, but it is complicated and must be performed by a surgeon experienced in this particular operation. In addition, Fran will need to be regularly evaluated for cancer of the stomach and small intestine as well, as the risk of developing cancer in these parts of the gut is also increased in FAP. Fran's cousins also face these difficult issues.

The Future

The family comes together to provide emotional support for the affected members, and the three affected individuals meet regularly to exchange information about the issues they're facing. Each of the three of them decides to undergo surgical removal of the colon and rectum. Because they are members of Genetic Health, they receive monthly reports about new developments in CRC research and about opportunities to join research studies designed for people in their situation. Fran and her cousins begin to feel that in spite of their increased risk they are taking steps to definitively reduce their risk, and they have a good chance of living long and productive lives.