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Cancer Health Center

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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...

Given these considerations, clinical decisions are based on clinical judgment. These decisions take into account the biologic and clinical behavior of each kind of genetic condition, and possible parallels with patients at average risk, for whom screening is known to be effective.

The evidence base for the effectiveness of screening in average-risk people (those without apparent genetic risk) is the benchmark for considering an approach to people at increased risk. (Refer to the PDQ summary on Screening for Colorectal Cancer for more information.)

The fact that screening of average-risk persons reduces the risk of dying from CRC forms the basis for recommending surveillance in persons at a higher genetic risk of CRC. As logical as this approach seems, randomized trials of surveillance have not been performed in this special population, though observational studies performed on families with LS [64,65] and FAP [66] support the value of surveillance. These studies demonstrate a shift towards earlier stage at diagnosis and a corresponding reduction in CRC mortality among colonoscopy-detected cancers.

(Refer to the Major Genetic Syndromes section of this summary for more information about surveillance in high-risk populations.)

Rationale for screening

Widely accepted criteria (1-3 below) for appropriate screening apply as much to diseases with a strong genetic component (more than one affected first-degree relative or one first-degree relative diagnosed at younger than 60 years) as they do to other diseases.[67,68] Additional criteria (4 and 5) were added below.[69]

  1. A high burden of suffering, in terms of morbidity, mortality, and loss of function.
  2. A screening test that is sufficiently sensitive, specific, safe, convenient, and inexpensive.
  3. Evidence that treating the condition when it is detected early, by screening, results in a better prognosis than treatment after it is detected because of symptoms.
  4. Evidence on the extent to which the screening test and treatment do harm.
  5. The value judgment that the screening test does more good than harm.

Of these criteria, the first and second are satisfied in genetically determined CRC. The harms of screening (criterion 4), especially major complications of diagnostic colonoscopy (perforation and major bleeding), are also known. Evidence that early intervention results in better outcomes (criterion 3) is limited but suggests benefit. One study in the setting of LS found earlier stage/local tumors in the screened individuals.[63]

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