Hereditary Colon Cancer: Which Patients Are at High Risk?
Ellen T. Matloff, MS, CGC is a certified genetic counselor and the president and CEO of My Gene Counsel, a company that provides updating, scalable digital genetic counseling for consumers and clinicians. Matloff founded the Yale Cancer Genetic Counseling program, served as its director and a faculty member at Yale School of Medicine for 18 years, and was a lead plaintiff in the SCOTUS BRCA gene patent case of 2013. She works closely with patient advocates in the areas of genetic counseling and testing, and direct-to-consumer (DTC) genetic testing, and is an expert in return of genetic test results and interpretation of genetic testing. Matloff serves as the Forbes.com contributor on genetic counseling, genetic testing, and digital health.
Colon cancer is equally as likely as breast and ovarian cancer to be hereditary (approximately 10% of cases, overall) and there are many different genes responsible for these cases.
Ellen T. Matloff, MS, CGC
Genetic testing for breast and ovarian cancer receives a lot of attention from the media, clinicians, patients, and the general public. Perhaps less well known is that colon cancer is equally likely to be hereditary (approximately 10% of cases, overall) and that there are many different genes responsible for these cases. Even less well known is that mutations that cause hereditary colon cancer can also increase the risk of several other cancers and physical findings. Patients may not realize, for example, that a family history of uterine cancer is relevant to their personal history of colon cancer. The oncology nurse can play a pivotal role in helping to elicit this history from the patient and determining which cases require a referral for genetic counseling.
Which of My Patients Are at Increased Risk for Hereditary Colon Cancer?
A personal history of early-onset colon cancer (<50 years), even in the absence of a family history, warrants a referral for genetic counseling. Similarly, a personal history of multiple polyposis warrants further investigation. Being aware of these and other risk factors (Table) can help you determine when to make referrals for genetic counseling and testing.
Many hospitals are now performing immunohistochemistry [IHC], as well as tests for microsatellite instability [MSI], on some, or all, colon and uterine cancers. These screening tests can help determine which of your patients are at increased risk for a hereditary cancer syndrome. Keep in mind that not all patients who screen positive truly have a hereditary cancer syndrome; they simply require a referral for counseling and testing. If your pathology department does not offer these screening tests, consider speaking to decision makers there about incorporating this important technology, at least in early-onset cases.
Table. Risk Factors for Hereditary Colon Cancer
Refer for genetic counseling if the patient has a personal and/or family history of:
Colon or endometrial (uterine) cancer diagnosed before the age of 50
Multiple cases of colon, uterine, or ovarian cancer on the same side of the family
Multiple and/or early-onset colon polyps, including greater than 15 gastrointestinal polyps, multiple polyposis, or greater than five hamartomatous or juvenile polyps
Related cancers, tumors, and/or physical findings in an individual or on the same side of the family (colon/ uterine/ovarian/urinary tract cancers, or colon cancer/polyps/desmoid tumors/osteomas)
Multiple primary colorectal and/or related cancers in one individual (eg, colon and uterine, synchronous/ metachronous colon cancers, colon and ovarian)
Rare or unusual tumors or physical findings (including even one sebaceous carcinoma or adenoma, or CHRPE)
Any HNPCC-related cancer/tumor (eg, colon, endometrial, sebaceous carcinoma) that is MSI-positive or demonstrates loss of an HNPCC-related gene product (ie, MLH1, MSH2, MSH6) by IHC
Known genetic mutation in the family (eg, HNPCC or FAP)
Genetic testing for colon cancer is evolving rapidly, and there will likely be more testing options within the next year. Presently, cases are split into two broad categories:
1) Polyposis syndromes (characterized by dozens, hundreds, or thousands of colon polyps):
- The number and types of polyps (adenomas, hamartomas, hyperplastic, etc) found determines which genes are likely involved. Obtaining pathology reports and a lifetime polyp count is therefore very important and can guide genetic testing.
- Multiple adenomatous polyps are most often associated with familial adenomatous polyposis (FAP). FAP can include osteomas, an eye finding called congenital hypertrophy of the retinal pigment epithelium (CHRPE), dental abnormalities, desmoid tumors, thyroid cancer, and medulloblastoma. All of these findings should be elicited when taking a pedigree.
2) Non-polyposis syndromes (characterized by no or few polyps):
- The best recognized is Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC).
- Colon cancer is often right-sided and early onset.
- Patients are also at increased risk for endometrial and ovarian cancers, sebaceous adenomas and carcinomas, and urinary tract cancers. Questions about all of these cancers should be asked when taking a pedigree.
- Colon and uterine tumors can be tested (via IHC screening or assessment of MSI) for markers to determine if the patient is at increased risk for Lynch syndrome; then, the patient should be offered genetic testing.
The oncology nurse can play an important role in taking a detailed personal and family history that includes all cancers, polyps, and related physical findings in order to determine which patients are at greatest risk for a hereditary cancer syndrome. Testing options for hereditary colon cancer will likely change with the advent of multiple gene panels and whole exome sequencing, so expect more testing options within the next two years.
Ellen T. Matloff, MS, CGC, is a certified genetic counselor and director of Cancer Genetic Counseling at Yale Cancer Center, New Haven, Connecticut.