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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)

Family HistoryRelative Risk of CRC[44]Absolute Risk (%) of CRC by Age 79 ya
CI = confidence interval.
a Data from the Surveillance, Epidemiology, and End Results database.
b The absolute risks of CRC for individuals with affected relatives was calculated using the relative risks for CRC[44]and the absolute risk of CRC by age 79 yearsa.
No family history14a
One first-degree relative with CRC2.3 (95% CI, 2.0–2.5)9b
More than one first-degree relative with CRC4.3 (95% CI, 3.0–6.1)16 b
One affected first-degree relative diagnosed with CRC before age 45 y3.9 (95% CI, 2.4–6.2)15b
One first-degree relative with colorectal adenoma2.0 (95% CI, 1.6–2.6)8b

When the family history includes two or more relatives with CRC, the possibility of a genetic syndrome is increased substantially. The first step in this evaluation is a detailed review of the family history to determine the number of relatives affected, their relationship to each other, the age at which the CRC was diagnosed, the presence of multiple primary CRCs, and the presence of any other cancers (e.g., endometrial) consistent with an inherited CRC syndrome. (Refer to the Major Genetic Syndromes section of this summary for more information.) Young subjects who report a positive family history of CRC are more likely to represent a high-risk pedigree than older individuals who report a positive family history.[48] Computer models are now available to estimate the probability of developing CRC. These models can be helpful in providing genetic counseling to individuals at average risk and high risk of developing cancer. At least three validated models are also available for predicting the probability of carrying a mutation in a MMR gene.[49,50,51]

Figure 1 shows the types of colon cancer cases that arise in various family risk settings.[52]

Figure 1. The fractions of colon cancer cases that arise in various family risk settings. Reprinted from Gastroenterology, Vol. 119, No. 3, Randall W. Burt, Colon Cancer Screening, Pages 837-853, Copyright (2000), with permission from Elsevier.

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