ABSTRACT
Purpose
With the recent guideline change for individuals at average risk for colorectal cancer
(CRC) to initiate colonoscopy at the age of 45 years, there is a need to provide an
updated counseling framework for individuals with variants in moderate-penetrance
CRC susceptibility genes.
Methods
Population age-specific incidence rates for CRC were obtained from the 2014-2018 US
Surveillance, Epidemiology, and End Results Program cancer statistics. Average-risk
multipliers derived from a systematic meta-analysis were used to calculate the 5-year
and cumulative lifetime risks for specific genetic variants associated with a moderate
risk for CRC: NM_007194.4(CHEK2):c.1100del (p.Thr367fs), NM_007194.4(CHEK2):c.470T>C
(p.Ile157Thr), NM_000038.6(APC):c.3920T>A (p.Ile1307Lys) and monoallelic MUTYH.
Results
When an individual at average risk would initiate colonoscopy at age 45 years, a CRC
risk of 0.39% is reached. For CHEK2 1100delC, CHEK2 I157T, and APC I1307K heterozygotes, this same level of risk is reached (or nearly reached) by age
40 to 45 years. For individuals with a monoallelic MUTYH variant, the CRC risk is 0.46% by age 45 to 49 years, similar to individuals at average
risk.
Conclusion
These updated calculations support recommendations to initiate earlier colonoscopy
surveillance for CHEK2 and APC I1307K germline variant heterozygotes. However, earlier surveillance is not indicated
for individuals with monoallelic MUTYH germline variants in the absence of family history.
Keywords
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Article info
Publication history
Published online: October 12, 2022
Accepted:
August 26,
2022
Received in revised form:
August 25,
2022
Received:
March 1,
2022
Identification
Copyright
© 2022 Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics.
