(Refer to the PDQ Summary on Prevention of Colorectal Cancer for more information.)
Genetic factors appear to influence the age at onset of CRC. People who have a first-degree relative with CRC are estimated to have an average onset of CRC about 10 years earlier than people with sporadic CRC. The increased cancer risk conferred by a family history of CRC appears to manifest itself primarily in people younger than 60 years. Markedly early onset of cancer is seen in hereditary conditions conferring an increased risk of CRC with a mean age at diagnosis of CRC in the early 30s for FAP and in the 40s for LS.[2,3]
For the most part, the effects of other nongenetic risk factors have not been evaluated in people who are genetically susceptible to CRC. Studies of carcinogen metabolic polymorphisms, such as glutathione S-transferase, N-acetyl transferase, and steroid 17-hydroxylase/17,20-lyase (CYP17), suggest that there may be some influence on the risk of CRC through interactions with micronutrients or other environmental factors; however, these data are too preliminary to apply in a clinical setting.[69,92,93,94,95]
In practical terms, knowing that a person is at an increased risk of CRC because of a germline abnormality is most useful if the knowledge can be used to prevent the development of cancer or cancer-related morbidity and mortality once it has developed. While one can also use the information for family planning, decisions about work and retirement, and other important life decisions, prevention is usually the central concern.
This section covers screening: testing in the absence of symptoms for CRC and its precursors (i.e., adenomatous polyps) to identify people with an increased probability of developing CRC. Those with abnormalities should undergo diagnostic testing to see if they have an occult cancer, followed by treatment if cancer or a precursor is found. Taken together, this set of activities is aimed at either preventing the development of CRC by finding and removing its precursor, the adenomatous polyp, or increasing the likelihood of cure by early detection and treatment.
Primary prevention (eliminating the causes of CRC in people with genetically increased risk) is addressed later in this section.
State of the evidence base
Currently there are no published randomized controlled trials of screening in people with a genetically increased risk of CRC and few controlled comparisons. While a randomized trial with a no-screening arm is not feasible, there is a need for well-designed studies comparing various screening methods or differing periods of time between screening procedures. A published observational study that compared screened with unscreened (by choice) controls evaluated a 15-year experience with 252 relatives at risk for LS, 119 of whom declined screening. Eight of 133 (6%) in the screened group developed CRC, compared with 19 in the unscreened group (16%, P = .014). In general, however, people with genetic risk have been excluded from the trials of CRC screening that have been published thus far, so it is not possible to estimate effectiveness by subgroup analyses. Therefore, prevention in these patients cannot be based on strong evidence of effectiveness, as is ordinarily relied on by expert groups when suggesting screening guidelines.