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Genetics of Colorectal Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Introduction

Table 1. Estimated Relative and Absolute Risk of Developing Colorectal Cancer (CRC) continued...

Interventions

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 whether 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.

In the context of high-risk syndromes such as LS or FAP, surveillance implies examining patients in whom adenoma or cancer occurrence is highly probable, and the examination is done for early detection. It is not screening in the traditional sense. The meaning of the terms screening versus surveillance has evolved over time and their usage in this summary may not be consistent with other oncologic and epidemiologic contexts.

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 surveillance in people with a genetically increased risk of CRC and few controlled comparisons. While a randomized trial with a no-surveillance arm is not feasible, there is a need for well-designed studies comparing various surveillance methods or differing periods of time between procedures. An observational study that compared surveilled subjects with unsurveilled (by choice) controls evaluated a 15-year experience with 252 relatives at risk of LS, 119 of whom declined surveillance. Eight of 133 (6%) in the surveilled group developed CRC, compared with 19 in the unsurveilled group (16%, P = .014).[67] 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 or surveillance guidelines.

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